Open access peer-reviewed chapter

Antioxidant Categories and Mode of Action

Written By

Manal Azat Aziz, Abdulkareem Shehab Diab and Abeer Abdulrazak Mohammed

Submitted: September 21st, 2018Reviewed: December 14th, 2018Published: November 6th, 2019

DOI: 10.5772/intechopen.83544

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Abstract

Oxidative stress has received a considerable scientific attention as a mediator in the etiology of many human diseases. Oxidative stress is the result of an imbalance between free radicals and antioxidants. Cells can be damaged by free radicals that are considered to play a main role in the aging process and diseases development. Antioxidants are the first line of defense against the detrimental effects of free radical damage, and it is essential to maintain optimal health via different mechanisms of action. Types of antioxidants range from those generated endogenously by the body cells, to exogenous agents such as dietary supplements. Antioxidant insufficiency can be developed as a result of decreased antioxidant intake, synthesis of endogenous enzymes, or increased antioxidant utilization. To maintain optimal body function, antioxidant supplementation has become an increasingly popular practice through improving free radical protection. In this chapter, we first elucidate the oxidative stress, and then define the antioxidant and its categories. Finally, introduce the antioxidants mode of actions for cell protection from free radicals.

Keywords

  • oxidative stress
  • antioxidants
  • reactive oxygen species
  • antioxidant enzymes
  • free radicals
  • antioxidant mechanisms

1. Introduction

Oxidative stress refers to the imbalance between oxidants and antioxidants within the body due to antioxidant deficiency or increased reactive oxygen species (ROS), reactive nitrogen species (RNA), and reactive sulfur species (RSS) production, which lead to potential cellular damage [1, 2]. ROS is a collective term that encompasses all highly reactive forms of oxygen, including free radicals. ROS categories include hydroxyl radical (OH), perhydroxyl radical (HO2), hypochlorous acid (HOCl), superoxide anion radical (O2•¯), hydrogen peroxide (H2O2), singlet oxygen (1O2), nitric oxide radical (NO), hypochlorite radical (OCl), peroxynitrite (ONOO), and different lipid peroxides. RNS are derived from nitric oxide by the reaction with O2•¯ to form ONOO¯, while RSS are easily produced from thiols through a reaction with ROS [3, 4].

Due to unpaired electrons of free radicals, these free radicals show high activity to react with other molecules in order to be neutralized. The free radicals have important functions in cell signaling, apoptosis, ion transportation, and gene expression [4]. Chemical reactivity of inactivated free radicals can damage all cellular macromolecules including carbohydrates, proteins, lipids, and nucleic acids. In general, cells are able to protect themselves against ROS damage via intracellular enzymatic reactions, metal chelating, and free radical scavenging actions to keep the ROS homeostasis at a low level. In addition, dietary antioxidants can assist to keep an adequate antioxidant status in the body. Nevertheless, during environmental stress and cell dysfunction, levels of ROS can increase dramatically and cause significant cellular damage in the body. Consequently, oxidative stress significantly contributes to the pathogenesis of different diseases, such as heart disease, inflammatory disease, cancer, diabetes mellitus, Alzheimer’s disease, autism, and to the aging process (Figure 1) [3, 4, 5]. The chapter clarifies oxidative stress. Then classify the antioxidants and their applications. Finally, we describe antioxidants’ mode of action and how they prevent the cell damage.

Figure 1.

Reactive oxygen species (ROS) generation by endogenous and exogenous sources can lead to oxidative damage and accumulation of proteins, lipids and DNA, when defensive (repair) mechanisms of the body become weak. These ROS also modulate the signal transduction pathways, which result in organelle damage, and changes in gene expression followed by altered responses of the cells, which finally results into aging. Adapted from Pandey and Rizvi [5].

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2. Oxidative stress

2.1 Oxidative damage to proteins

Protein oxidation can lead to amino acid modification, fragmentation of the peptide chain, aggregation of cross-linked reaction products, and increased electrical charges. Oxidized proteins are more susceptible to proteolysis, and a raise in oxidized proteins may be responsible for the loss of selected physiological and biochemical roles. Free radical damage to proteins may play a role in the causation of cataracts and aging (Figure 2) [1, 6].

Figure 2.

A schematic diagram illustrating the detrimental effects of free radicals on biomolecules. Adapted from Law et al. [1].

2.2 Oxidative damage to lipids

Lipids have an important structural and functional role in cell membranes. After cell death, membrane lipids are susceptible to peroxidation and this process can cause misinterpretation of some lipid peroxidation assays. In particular, polyunsaturated fatty acids are susceptible targets for ROS attack. The important reactive moiety and initiator for ROS chain reaction and lipoperoxidation of polyunsaturated is OH [7]. Because of lipid peroxidation, several compounds are produced, such as alkanes, malondialdehyde, and isoprostanes. These compounds are utilized as indicators in lipid peroxidation assay, and have been confirmed in diseases including neurogenerative diseases, heart disease, and diabetes (Figure 2) [1, 8].

2.3 Oxidative damage to DNA

Activated oxygen and agents that produce oxygen-free radicals, for example, ionizing radiations, promote damage in DNA that leads to deletion, mutations, and other fatal genetic effects. Through this DNA damage, both sugar and base moieties are susceptible to oxidation, leading to base degradation, single-strand breakage, and cross links to proteins. Free radical damage to DNA is associated in the causation of cancer and accelerated aging (Figure 2) [1, 5, 9].

2.4 Oxidative damage to carbohydrates

According to carbohydrates, the production of oxygen-free radicals during early glycation could contribute to glycoxidative damage. Through the primary stages of nonenzymatic glycosylation, fragmentation of sugar forms short-chain species like glycoaldehyde whose chain is too short to cyclize and is thus prone to autoxidation, producing the superoxide radical that can lead to the formation of β-dicarbonyls, which are well-known mutagens [10]. Carbohydrates free radical oxidation mechanisms are comparable to those of lipids. Low molecular carbohydrates, such as glucose, mannitol, and deoxyribose, are well known to interact with HO, forming oxidized intermediates, which does not affect food quality [11].

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3. Antioxidants

Antioxidants are inhibitors of oxidation, even at small concentrations; therefore, antioxidants have different physiological functions in the body. In addition, antioxidants act as free radical scavengers, by reacting with the reactive radicals and demolishing them to become less active, less dangerous, and long-lived substance than those radicals that have been neutralized. Antioxidants may be able to neutralize free radicals via accepting or donating electron(s) to remove the unpaired status of the radical [4]. Also, antioxidants can be defined as compounds able to inhibit oxygen-mediated oxidation of different substances from simple molecule to polymer and complicated bio-system [8].

The US Food and Drug Administration (FDA) defined antioxidants as substances utilized to preserve food by retarding deterioration, rancidity, or discoloration owing to oxidation. Whereas antioxidants are important to the food industry to prevent rancidity, antioxidants are also important to biologists and clinicians as they may assist to protect the human body against diseases from ROS danger by regulating ROS-related enzymes [8]. Cellular level of free radicals may be decreased by antioxidants either via inhibiting the activities or expression of free radical generating enzymes such as NAD(P)H oxidase and xanthine oxidase (XO), or by promoting the activities and expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [12, 13, 14].

Since 1990s, antioxidant research has increased dramatically due to its potential role in disease prevention and health promotion. In biological systems such as animal models and clinical trials, the antioxidant action of pure compounds, foods, and dietary supplements has been extensively examined [4, 15, 16]. Numerous study models have been determined in chemical and/or biological systems to examine the mechanism of action of antioxidants, as well as the identification and recognition of new antioxidants, particularly from natural substances. Further research in animal models and cell cultures has provided critical information on the bioavailability, metabolism, and toxicity issues of antioxidants, suggesting probable clinical applications of these substances. Nevertheless, animal models and human research are expensive and not suitable for early antioxidant screening of foods and dietary supplements. Therefore, cell culture models have been utilized for early screening and study proceeding to animal research and human clinical trials [4].

Antioxidants can protect the cells and organs of the body against the harmful effect of the oxidative stress through various defense mechanisms by both enzymatic and nonenzymatic reactions, which work synergistically and together with each other. To prevent lipid peroxidation in food, nonenzymatic antioxidants are often added. The use of antioxidants for food and therapeutic purposes must be characterized carefully, because several lipid antioxidants can exert a prooxidant effect to other molecules under particular circumstances [5, 7].

The feature of a perfect antioxidant is that it should be readily absorbed, eliminate free radicals, and chelate redox metals at physiologically suitable levels. In addition, it should work in both aqueous and membrane domains, and have a positive effect on gene expression [7].

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4. Antioxidant categories

Antioxidants can be classified in several ways [17, 18].

  1. Based on their activity, they can be classified as enzymatic and nonenzymatic antioxidants. Dangerous oxidative products can be converted to H2O2 and then to water by enzymatic antioxidants that are able to break down and get rid of free radicals in a multistep process in the presence of cofactors such as copper (Cu), zinc (Zn), manganese (Mn), selenium (Se), and iron (Fe).

  2. Vitamin C, vitamin E, plant polyphenol, carotenoids, and glutathione are nonenzymatic antioxidants, which act by interrupting free radicals chain reactions.

  3. Based on solubility, antioxidants can be classified as water-soluble or lipid-soluble antioxidants. Vitamin C is a type of water-soluble vitamin found in cellular fluids such as cytosol or cytoplasmic matrix.

  4. According to size, antioxidants can be categorized as small or large-molecule antioxidants. The small molecule antioxidants neutralize the ROS in a process named radicals scavenging and carry them away. Vitamin C, vitamin E, carotenoids, and glutathione (GSH) are the main antioxidants in this category. Large molecule antioxidants include enzymes (SOD, CAT, and GPx) and sacrificial proteins (albumin) that absorb ROS and prevent them from attacking other essential proteins.

  5. Kinetically antioxidants can be categorized as below:

    1. Antioxidants that are able to break chains through reacting with peroxyl radicals containing weak O–H or N–H bonds, phenol, naphthol, hydroquinone, aromatic amines, and aminophenols.

    2. Antioxidants with a capability to break chains by reacting with alkyl radicals: quinines, nitrones, and iminoquinones.

    3. Antioxidants that terminate cyclic chain such as aromatic amines, nitroxyl radicals, and variable valence metal compounds.

    4. Hydroperoxide decomposing antioxidants such as sulfide, phosphide, and thiophosphate.

    5. Metal-deactivating antioxidants include diamines, hydroxyl acids, and bifunctional compounds.

    6. Synergism action of a number of antioxidants including phenol sulfide in which the phenolic group reacts with the peroxylradical’s sulfide group with hydroperoxide.

  6. Based on their occurrence, antioxidants are categorized as natural or synthetic [19, 20].

  1. Natural antioxidants

    They are classified as chain-breaking antioxidants, which react with radicals and convert them into more stable products. Generally, antioxidants of this group are phenolic in structure and include the following:

    1. Antioxidant minerals: these are antioxidant enzymes cofactors like selenium, copper, iron, zinc, and manganese. Absence of the cofactors will definitely enhance many macromolecules metabolism such as carbohydrates.

    2. Antioxidant vitamins: these are important and required for most body metabolism functions such as, vitamin C, E, and B.

    3. Phytochemicals: these are phenolic compounds derivatives that are neither vitamins nor minerals. Examples include flavonoids, catechins, carotenoids, carotene, lycopene, and herbs and spices such as diterpene, rosmariquinone, thyme, nutmeg, clove, black pepper, ginger, garlic, curcumin, and derivatives.

  2. Synthetic antioxidants

    These are phenolic compounds that carry out the role of capturing free radicals and stopping the chain reaction. These compounds include butylated hydroxyl anisole (BHA), butylated hydroxyltoluene (BHT), propyl gallate (PG), metal chelating agent (EDTA), tertiary butyl hydroquinone (TBHQ), and nordihydroguaiaretic acid (NDGA).

4.1 Antioxidant enzymes

There are several enzymes that catalyze reactions to neutralize free radicals and ROS. These enzymes form the body’s endogenous defense mechanisms from free radicals to protect the cell. The enzyme antioxidants GPx, CAT, and SOD are the best-known substances of the antioxidant protection system, and they are responsible for the free radical change [21]. Enzymes are important components of the protection and defense mechanisms, by decreasing ROS generation via removing potential oxidants/transferring ROS/RNS into relatively stable compounds [5]. For optimum catalytic activity, these enzymes require micronutrient cofactors such as Se, Fe, Cu, Zn, and Mn [21].

4.1.1 Superoxide dismutase (SOD)

Irwin Fridovitch of Duke University and Joe McCord discovered antioxidant enzyme (SOD) (EC 1.15.1.1) in 1967, which belongs to the group of oxidoreductases. SOD is an important cellular defense against free radical damage. Therefore, medical scientists have begun to look seriously at free radicals [3]. SOD antioxidant enzymes are metal-containing proteins that catalyze the dismutation of the highly reactive superoxide anion to O2 and to the less reactive species H2O2 (Eq. (1)). The result is that peroxide can be destroyed by reaction of CAT or GPX [22, 23].

O2+O2+2H+SODH2O2+O2E1

In mammals, there are three forms of SOD; the active site of the enzyme contains one or two different atoms of a transition metal in a certain oxidation state. SODs are categorized by their metal cofactors into known forms: cytosolic SOD, extracellular SOD [CuZnSOD], and mitochondrial SOD [MnSOD]. Each form is produced by distinct genes and distinct subcellular localization, but catalyzes the same reaction. This distinct subcellular localization of the three SOD forms is especially significant for compartmentalized redox signaling [24].

CuZnSOD enzymes have two identical subunits of about 32 kDa, though a monomeric structure is found in a high concentration of protein from E. coli. Each subunit includes a metal cluster, an active site, and a Cu and a Zn atom bridged By a histamine residue. The Cu and Zn which are important for SOD enzymatic activity. Zn contributes in appropriate protein folding and stability. Cu is not replaceable with another metal, while Zn is replaceable with cobalt and Cu, and it is not essential for enzyme action at low pH. CuZnSOD plays a major function in the first line of antioxidant defense [25].

MnSOD is a homotetramer 96 kDa; each subunit contains one Mn atom, those cycles from Mn3+ to Mn2+ and back to Mn3+ during the two-step dismutation of superoxide. In mitochondria, the main source of oxygen radicals is the respiratory chain. It was shown that this enzyme is greatly stimulated and decreased by cytokines, while oxidants moderately influenced it [26, 27, 28].

Extracellular SOD (ECSOD) is a tetrameric protein, containing Cu and Zn having a high affinity for certain glycosaminoglycans such as heparin and heparin sulfate [7]. ECSOD is found primarily in the extracellular membrane and to a lesser extent, in the extracellular fluids. It protects against the inactivation of NO liberating from the endothelium by O2¯ through diffusion to smooth muscle, thus preserving endothelial function. Studies have shown that ECSOD plays an essential role in various oxidative stress-dependent pathophysiologies, such as hypertension, ischemia reperfusion injury, and lung injury. In addition, a number of lines of research propose a role for ECSOD in aging. ECSOD plasma levels decrease with aging, and in old rats, gene transfer of ECSOD improves endothelial function. However, it is still unknown whether ECSOD expression or activity in blood vessels is adjusted by aging and whether endogenous ECSOD is engaged in regulation of vascular functions during aging [29].

4.1.1.1 Application

SOD enzymes enhance the rejuvenation and cellular repair, while decreasing the damage caused by free radicals. SOD is necessary to generate sufficient amounts of skin building cells named fibroblasts and plays an essential role in preventing the progress of amyotrophic lateral sclerosis (ALS), which causes death if it affects the nerve cells in the spinal cord and brain. In addition, this enzyme is also utilized for inflammatory diseases treatment, burn injuries, prostate problems, corneal ulcer, arthritis, and reversing the long-term consequences of radiation and smoke exposure. Furthermore, it prevents wrinkle formation if the skin lotion contains this enzyme. Also, it enhances wound healing, reduces scars, and lightens skin pigmentation caused by UV rays.

Moreover, SOD facilitates nitric oxide moving into hair follicles. This is beneficial for people with a genetic predisposition or free radicals for premature hair loss. SOD is a very potent antioxidant, in that it combats the effect of free radicals on the hair follicles. Because of nitric oxide’s ability as a blood vessel relaxant, allowing more blood to reach the hair follicle, and SOD ability to remove free radicals, hair loss can be prevented or reversed. Maintaining overall well-being and health, as well as free radical protection, can be achieved by taking dietary supplement that provides an adequate supply of SOD [3].

4.1.2 Catalase (CAT)

Catalase (EC 1.11.1.6) is an enzyme responsible for H2O2 degradation that is generated by oxidases involved in β-oxidation of fatty acids, respiration, and purine catabolism [3]. It is present in nearly all animal cells as a protective enzyme. The highest levels of CAT activity are measured in the liver, kidney, and red blood cells.

Human CAT composes four identical subunits of 62 kDa, each subunit containing four distinct domains and one prosthetic heme group, and has a molecular mass of about 240 kDa [30]. CAT enzyme reacts with H2O2 to form water and molecular oxygen and with H donors such as methanol, ethanol, formic acid, or phenols with peroxidase activity. CAT protects cells from H2O2 generated within them. Therefore, it has an essential role in the acquisition of tolerance to oxidative stress in the adaptive response of cells. Various disease conditions and abnormalities are associated with the deficiency or mutation of CAT enzyme [30, 31].

4.1.2.1 Application

In the food industry, CAT enzyme is used to remove H2O2 from milk prior to cheese production, and to prevent food from oxidizing in food wrappers. In addition, CAT enzyme is used in the textile industry for H2O2 removal from fabrics, to make sure the material is peroxide free. Recently, esthetics industries have begun to use CAT enzyme in facial masks, as the combination of CAT enzyme with H2O2 on the face can be used to increase cellular oxygenation in the upper layers of the epidermis [3].

4.1.3 Glutathione perioxidases (GPx)

Glutathione peroxidase (EC 1.11.1.9) contains a single selenocysteine residue in each of the four identical subunits, which is important for enzyme activity. GPx (80 kDa) is an imperative intracellular enzyme that catalyzes H2O2 to water and lipid peroxides to their corresponding alcohols mainly in the mitochondria and sometimes in the cytosol. In mammals, there are five GPx isoenzymes. Though their expression is ubiquitous, the level of each isoform differs depending on their tissue type. Mitochondrial and cytosolic glutathione peroxidase (GPx1 or cGPx) reduces fatty acid hydroperoxides and H2O2 at the expense of glutathione [32].

GPx1 is the main ubiquitous selenoperoxidase present in most cells; found in the cytosolic, mitochondrial, and peroxisomal compartments. It is an important antioxidant enzyme required in the detoxification of H2O2 and lipid hydroperoxides and preventing DNA, protein and lipids damage by harmful accumulation of intracellular H2O2 [33]. GPx1 uses GHS as an obligate co-substrate in the reduction of H2O2 to water [32]. Phospholipid hydroperoxidase glutathione (PHGPX) is found in most tissues and can directly reduce the phospholipid hydroperoxides, fatty acid hydroperoxides, and cholesterol hydroperoxides that are produced in peroxidized membranes and oxidized lipoproteins [30].

GPx4 is found in both the cytosol and the membrane fraction, and is highly expressed in renal epithelial cells and tests. Cytosolic GPx2 or extracellular GPx3 is inadequately found in nearly all tissues except for the gastrointestinal tract and kidney. In recent, GPx5, a new kind, expressed particularly in mouse epididymis, is selenium independent [34].

Several studies underlined the clinical importance of GPx. In addition, GPx, especially GPx1, have been implicated in the progression and prevention of many frequent and complex diseases, including cancer and cardiovascular disease [34, 35].

4.1.3.1 Application

GPx is an important antioxidant enzyme in the body. Glutathione (GHS), the master antioxidant, is important for GPx levels due to the closely linked relationship; GHS is a tripeptide that protects the cells against the negative effects of pollution and functions as the body’s immune system booster. GHS plays an essential role in red blood cells to remain intact and protects white blood cells, which are responsible for the immune system. An antioxidant’s role is specifically essential for the brain because it is sensitive to the presence of free radicals. To increase the body’s protection from free radicals, it is imperative to combine certain antioxidants such as glutathione, vitamin C and E, Se, and GPx [3].

4.2 Nonenzymatic antioxidants

In previous decades, there has been increasing evidence that large amounts of antioxidants present in our diet contribute to the antioxidant defense system by preventing oxidative stress and specific human diseases. Phytochemicals, the plant-derived compounds, are one of the classes of the dietary factors, which play an essential role in functions of the body. Food materials contain a number of natural compounds reported to have antioxidant characteristics due to the presence of hydroxyl groups in their structure. Synthetic and natural antioxidants prevent the oxidative damage to the most important macromolecules such as lipids, proteins, and nucleic acids found in human body through scavenging the free radicals formed in different biochemical processes [36]. These antioxidants consist of small molecules including vitamin C, E, and β-carotene or natural antioxidants such as flavonoids, tannins, coumarins, phenolics, and terpenoids [37]. Because of oxidative stress, the free radicals that have been produced react with lipids, proteins and nucleic acids and lead to stimulation of apoptosis, which causes various neurological, cardiovascular, and physiological disorders [38].

In addition to phytochemical antioxidants, which can protect the body from oxidative damage, there are other antioxidants for example polyphenols, lycopene, and lutein [39]. Even though there has been a considerable concentration on antioxidant function of phytochemicals for several years, it is distinguished that phytochemicals have nonantioxidant effects important for health such as cell signaling and gene expression [40].

4.2.1 Glutathione

Glutathione (γ-glutamyl-cysteinyl-glycine; GSH) is a tripeptide and is the most abundant intracellular antioxidant protecting normal cells from oxidative injury due to its role as a substrate of ROS scavenging enzymes. Glutathione is primarily present in its reduced form (GSH) in normal conditions, with only a small amount being found in the fully oxidized state (GSSG) [41]. Glutathione functions as a nonenzymatic antioxidant through free radical scavenging in cells and serves as a cofactor for several enzymes, include GPx, glutathione reductase (GR), and glutathione transferase (GST) [42, 43].

4.2.1.1 Application

Recently, there is a new era of therapeutic applications of glutathione through the association of decreased GSH levels with the common features of aging and a wide range of pathological conditions, including neurodegenerative disorders. Remarkably, depletion and alterations of GSH in its metabolism appear to be crucial in the onset of Parkinson’s disease [44].

4.2.2 Vitamin E

Vitamin E, C, and β-carotene are the main antioxidant vitamins for tissues against free radical damage. Vitamin E, a major lipid soluble antioxidant, functions as the most important membrane-bound antioxidant, neutralizing free radicals, and preventing oxidation of lipids within membranes [45]. Vitamin E is the free radical scavenger in the prevention of chronic diseases [46]. α-Tocopherol is the main form of vitamin E with antioxidant and immune functions. α-tocopherol has been revealed to be a more effective inhibitor of peroxynitrite-induced lipid peroxidation and inflammatory reactions [47]. In vitrotocotrienols have excellent antioxidant activity and have been proposed to restrain ROS more effectively than tocopherols [48].

4.2.2.1 Application

The main function of vitamin E is to protect against lipid peroxidation through evidence suggesting that α-tocopherol and vitamin C function together in a cyclic type of process. It has been reported that vitamin E supplementation in hypercholesterolemic patients has shown to increase autoantibody levels against oxidized LDL, and prevent ischemic heart disease [49].

4.2.3 Vitamin C

In extracellular fluids, vitamin C, a water-soluble vitamin, is the most important antioxidant and can protect biomembranes against lipid peroxidation injury through eliminating peroxyl radicals in the aqueous phase before peroxidation initiation. Vitamin C is an effective antioxidant located in the aqueous phase of cells; it simply loses electrons to give stability to reactive species such as ROS [45]. In addition to vitamin C’s biological functions as a superoxide and hydroxyl radicals’ scavenger, it also functions as an enzyme cofactor [42].

4.2.3.1 Application

Vitamin C plays an essential function in the defense against oxidative damage particularly in leukocytes, as well as the possible effect it may have on the treatment of chronic degenerative diseases, autoimmune diseases, and cancer [42, 45].

4.2.4 Carotenoids

Carotenoids are structurally and functionally different natural pigments found in many fruits and vegetables. A combination of carotenoids and tocopherols antioxidants in the lipid phase of biological membranes may enhance better antioxidant protection than tocopherols alone. Antioxidant characteristics of carotenoids include scavenging single oxygen and peroxyl radicals, thiyl, sulfonyl, sulfur, and NO2 radicals and giving protection to lipids from superoxide and hydroxyl radical attack [49].

4.2.4.1 Application

Carotenoids and some of their metabolites are proposed to play a protective function in several ROS-mediated disorders, include cardiovascular, cancer, and myocardial infarction among smokers. Carotenoid-rich food and supplementation decrease morbidity in nonsmokers and reduce the risk of prostate cancer [42].

4.2.5 Vitamin A

Vitamin A, a lipid soluble vitamin, is important for human health and has free radicals scavenging features that aid it to act as a physiological antioxidant in protecting a number of chronic diseases such as cardiovascular disease and cancer. All transretinol, the parent compound, are the most abundant dietary form of vitamin A that occurs naturally in the form of fatty acid esters such as retinyl palmitate, while retinal and retinoic acid are the minor natural dietary components of vitamin A [45]. Vitamin A was first labeled as an inhibitor of the effect of linoleic acid on the oxidation processes. At present, vitamin A and carotenoids are known for their antioxidant actions depending on their capability to interact with radicals and prohibit cell lipid peroxidation [9].

4.2.5.1 Application

Vitamin A is important for life in mammals; it cannot be synthesized in body and has to be supplied by food. Due to its role as antioxidant, vitamin A has a new role in preventive nutrition against neurodegenerative diseases. Recently, vitamin A has increased the interest in supplementation via food [50].

4.2.6 Uric acid

Uric acid, hyperuricemia, is a potent free radical scavenger and estimated ~60% of free radical scavenging capacity in plasma [51]. Uric acid is a physiological antioxidant and an effective preventer of the production of ROS species during the action of xanthine oxidase (XO) in catalysis reaction of xanthine and hypoxanthine [42]. A study illustrated the urate ability to scavenge oxygen radicals and protect the erythrocyte membrane from lipid oxidation, characterized further by Ames et al. through the effect of uric acid in protection of cells from oxidants, which related to a variety of physiological situation [51]. Nevertheless, it is probable that the increase in serum level of uric acid is a response to protect against the detrimental effects of extreme free radicals and oxidative stress [52].

4.2.6.1 Application

Studies showed that serum uric acid levels are highly predictive of mortality in patients with coronary artery disease, heart failure, or diabetes. In addition, high uric acid level is associated with deleterious effect on vascular function. Recently, it has been found that patients with high serum uric acid level had impaired flow-mediated dilation, which was normalized by therapy for 3 months with the xo inhibitor allopurinol [53].

4.2.7 Lipoic acid

Lipoic acid is a strong antioxidant, and it reveals a great capability of antioxidant when given natural or as a synthetic drug. Lipoic acid is a short-chain fatty acid, composed of sulfur in their structure that is known for its contribution in the reaction that catalyzes the oxidation decarboxylation of α-keto acids, for example pyruvate and α-ketoglutarate, in the citric acid cycle. Lipoic acid and its reduced form, dihydrolipoic acid (DHLA), are capable of quenching free radicals in both lipid and aqueous domains. Lipoic acid and DHLA have been revealed to have antioxidant, cardiovascular, antiaging, detoxifying, anti-inflammatory, anticancer, and neuroprotective pharmacological properties [40, 54].

4.2.7.1 Application

Regarding the pathology of diabetes, there are many potential applications for lipoic acid. In type I diabetes, destruction of pancreatic β-cells leads to loss secretion of insulin, while the major problem in type II diabetes is insulin resistance of peripheral tissues. Lipoic acid has potential preventive or ameliorative effect in both type I and type II diabetes [54].

4.2.8 Flavonoids

Flavonoids are low in molecular weight and are the main type of phenolic compounds in plants. They are structured by 15 carbon atoms, organized in a C6-C3-C6 configuration. Due to their high redox potential, flavonoids are, in particular, important antioxidants that allow them to function as reducing agents, hydrogen donors, and singlet oxygen quenchers. In addition, they include a metal chelating potential [55].

4.2.8.1 Application

Flavonoids are generally found in many fruits and vegetables. When human increasingly consumed it, flavonoids have been linked with a decrease in the incidence of diseases such as prostate [56, 57] or breast cancer [58, 59].

4.2.9 Tannins

Tannins are relatively high-molecular compounds, which comprise the third essential group of phenolics and can be divided into condensed and hydrolysable tannins. Condensed tannins are produced by the polymerization of flavonoid units. The mainly studied condensed tannins are based on flavan-3-ols: (−)-epicatechin and (+)-catechin. Hydrolysable tannins are heterogeneous polymers containing phenolic acids, in particular, gallic acid (3,4,5 trihydroxyl benzoic acid) and simple sugar [42, 55].

4.2.9.1 Application

Because of tannin features, such as being the potential metal ion chelators, protein-precipitating agents, and biological antioxidants, tannins have different effects on biological systems. As a consequence of the diverse tannins biological roles and structural variation, it has been difficult to modify models that would let a precise prediction of their effects in any system. Therefore, the tannin structure modification and activity relationship are important to predict their biological effect [42].

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5. Antioxidants: mechanisms of action

Generally, the antioxidants defend against free-radicals-induced oxidative damage by various mechanisms as discussed in below sections.

5.1 Preventive antioxidants

ROS such as H2O2, O2, and OH are produced irreversibly during metabolism. Therefore, methods have been extensively studied to reduce the damage enhanced by oxidative stress. Intracellular antioxidant enzymes produced in the cell are an essential protective mechanism against free radicals formation. SOD, CAT, GPx, GR, GST, thioredoxin reductase, and hemeoxygenase are the most important antioxidants enzymes. SODs convert O2 into H2O2, which is then converted into water by CAT, GPx, and Fenton reaction. Thus, two toxic species are converted into a harmless product (Figure 3) [5].

Figure 3.

Antioxidant enzyme system, O2, is dismutaed toH2O2 by SOD enzyme. The resulted H2O2 is converted into water by CAT and GPx. In this way, two toxic species, O2 and H2O2, are converted into the harmless product water. GPx neutralized H2O2 via taking hydrogen from two GSH molecules forming two molecules of water and GSSG. GR then regenerates GSH from GSSG. CAT, the essential part of enzymatic defense, neutralizes H2O2 into water. By Fenton reaction, H2O2 is also converted to the highly reactive OH and then to water through oxidation of Fe2+ to Fe3+. Adapted from Pandey and Rizvi [5].

During metabolism, peroxides are formed and then eliminated via both GST and GPX. GRd regulates the equivalent of GSH and oxidized glutathione (GSSG), and the ratio of GSH/GSSG is a known index of oxidative stress [60]. The action of GRd plays an imperative role in increasing GSH concentration, which maintains the oxido-redox condition in the organism [14]. Consequently, the oxidative stress role has been reported in the progress and clinical symptom of autism. Recently, a comparison study between autism and control individuals showed decrease in GSH/GSSG ratio and increase in free radical generation in autism compared to control cells [60]. In addition, GPx is presented throughout the cell, while CAT is frequently limited to peroxisomes. In the brain, which is very sensitive to free radical damage, it has seven times more GPx activity than CAT activity. Moreover, CAT’s highest levels are found in the liver, kidney, and erythrocytes, where it decomposes the most of H2O2 [61].

5.2 Free radical scavengers

5.2.1 Scavenging superoxide and other ROS

Superoxide (O2•¯), a predominant cellular free radical, is contributed in a huge number of deleterious alterations often linked to a low concentration of antioxidants and associated with a raise in peroxidative processes. Though O2•¯ itself is not reactive to biomolecules, it assists in production of stronger OH•, and ONOO¯.O2•¯ is formed in large quantities, in phagocytes via NADPH oxidase enzyme during pathogen-killing process. In addition, it is a byproduct of mitochondrial respiration [3].

5.2.2 Scavenging hydroxyl radical and other ROS

Hydroxyl radical (OH) is an extremely active and more toxic radical on biologic molecules such as DNA, lipids, and proteins than other radical species. In general, OH is considered to be formed from the Fe2+ or Cu+/H2O2 Fenton reaction system, through incubation FeSO4 and H2O2 in aqueous solution. Therefore, antioxidants activity as OH scavenger can be accomplished by direct scavenging or prohibiting of OH generation by the chelation of free metal ions or altering H2O2 to other nontoxic compounds [3].

5.2.3 Metal ion (Fe2+, Fe 3+, Cu2+, and Cu+) chelating

Even though trace minerals are essential dietary components, they can function as prooxidants (through enhancing formation of free radicals). Fe2+ and Cu+ react with H2O2, which is a product produced by the dismutation of the O2•¯ via SOD, to form extremely reactive OH (Eq. (2)). Dissimilarly, iron and copper’s reaction with H2O2 forms more singlet oxygen than OH. Fe2+ and Cu+ are oxidized to Fe3+ and Cu2+, respectively. Cellular reductant such as NADH and oxidized metal ions Fe3+, and Cu2+ are reduced and permit the recycling to react with another molecule of H2O2 to produce OH radical in the presence of vitamin C (Eq. (3)). OH is strongly reactive and can directly react with proteins and lipids to produce carbonyls (aldehydes and ketones), cross linking, and lipid peroxidation. Chelating metal ions are able to decrease their action, thus reducing the ROS formation.

Fe2+orCu++H2O2Fe3+orCu2++OH+OHE2
Fe3+orCu2++vitCHFe2+orCu++vitaminC+H+E3

Studies showed that Se antioxidant is able to chelate Cu+ (formed in situ with Cu2+/ascorbic acid) extremely efficiently and prevent the damage of DNA by OH radical (formed via Cu+/H2O2) [3].

5.3 Free radical generating enzyme inhibitors

It has been reported that the main sources of free radicals in different physiological and pathological conditions is associated with a number of enzymes. NADPH oxidases are a type of plasma membrane linked enzymes that have an ability to transfer one electron from the cytosolic donor NADPH to a molecule of extracellular oxygen, forming O2•¯ [62]. Uric acid is formed by xanthin oxidase enzyme through catalyzing the oxidation of hypoxanthine and xanthin to uric acid yielding O2•¯ and H2O2 and increase the oxidation level in an organism [63]. In addition, O2•¯ is also formed as a by-product of mitochondrial respiration as well as several other enzymes, for example NADH oxidase, monooxygenases and cyclooxygenases. O2•¯ is biologically quite toxic and is produced in significant amounts by the enzyme NADPH oxidase to be used in oxygen dependent killing mechanisms for invading pathogens. During the respiratory burst, it is an important control of reactive oxygen derivatives production for the defense of an organism against invading microorganisms, without causing an important loss of tissue functions [3]. Nonetheless, excessive ROS enhance oxidative stress such as low density lipoprotein (LDL) oxidation. A direct link between elevated phagocytic NADPH oxidase activities and increased circulating oxidized LDL in metabolic syndrome patients has been found. As a result, both modulation of NADPH oxidase to prohibit ROS overproduction and antioxidants supplementation have been reported as active strategies to prevent the deleterious effect of oxidative stress in hemodialysis patients [64]. In recent years, many natural antioxidants have revealed potential to inhibit enzymes that promote O2•¯ generation as well as the development of new therapeutic agents for oxidative stress-related diseases [3].

5.4 Prevention of lipid peroxidation

Lipid peroxidation is defined as oxidative deterioration of lipids composed of C-C double bonds such as unsaturated fatty acids, glycolipids, cholesterol, cholesterol ester, phospholipids. ROS damage the unsaturated fatty acids, which include numerous double bonds and the methylene-CH2-groups with particularly reactive hydrogen atoms, and begin the radical peroxidation chain reactions [65]. Antioxidants are able to directly react and quench peroxide radicals to stop the chain reaction. Lipid peroxidation and DNA damage are related to different chronic diseases, such as cancer, and atherosclerosis. Antioxidants can scavenge ROS and peroxide radicals, therefore prohibiting or treating certain pathogenic situations. Scientific attention has been concentrated in lipid peroxidation for recognizing natural antioxidants and studying their mechanism of action. Researches on antioxidants such as vitamins, polyphenols and flavones against free radical enhanced lipid peroxidation have been assumed in many systems such as lipid, red blood cells and LDL. The antioxidant activity of these polyphenols depends considerably on molecules structure, the initiation conditions and the microenvironment of the reaction medium [3].

5.5 Prevention of DNA damage

In vivo, the OH and ONOO¯ radicals produced from nitric oxide and O2•¯ are able to react directly with plasmid DNA macromolecules to cleave one DNA strand, leading to oxidative DNA damage. Cell death and mutation as a result of DNA damage are associated with neurodegenerative and heart diseases, cancer and aging. Consequently, DNA or plasmid damage has received attention and been utilized as models for the study and identification of antioxidants [66]. A study has been progressed include DNA damage caused by Cu+ induced OH, through metal-free plasmid DNA mixed with Cu2+, ascorbic acid and H2O2 at pH 7. The reaction includes reduction of Cu2+ to Cu+ in situ with ascorbic acid. The OH radical formed via Cu+/H2O2 cleaves one DNA strand, causing the ordinarily supercoiled plasmid DNA to unwind [3].

5.6 Prevention of protein modification

Besides lipid peroxidation and DNA damage, protein modification through nitration or chloration of amino acids also is caused by ROS. In vivo, peroxynitrite, O═N─O─O¯, is a powerful oxidant and nitrating agent formed through the reaction of O2•¯ with free radical nitric oxide via a diffusion-controlled reaction. In cells, ONOO¯ is a much stronger oxidizing agent than O2•¯ and is able to damage a wide range of different molecules such as DNA and proteins. ONOO¯ and its protonated form peroxynitrous acids (ONOOH) are capable of exerting direct oxidative modifications during one or two electron oxidation processes [67]. In vivo, ONOO¯ reacts nucleophically with CO2 to produce nitrosoperoxy carbonate, which is the predominant pathway for ONOO¯. These modifications often cause the alteration of protein function or structure, in addition to enzyme activities inhibition. Proteins containing nitrotyrosine residues have been detected in various pathogenic conditions, such as diabetes, hypertension, and atherosclerosis, all linked with promoted oxidative stress, including increased formation of ONOO¯. Antioxidants and antioxidant enzyme are utilized to prevent the protein modification of ONOO¯. Antioxidants or enzyme such as CAT is able to remove H2O2 and also inhibit HOCl formation; similarly, SOD or antioxidants, like polyphenols, may scavenge O2•¯ and inhibit ONOO¯ formation [3].

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6. Conclusion

This chapter briefly summarized types of antioxidants, and their mode of action. The harmful products formed during normal cellular functions are oxygen radical derivatives that are the most important free radical in the biological system. For normal physiological functioning, it is important to maintain a tolerated antioxidant status by increasing intake of natural antioxidants. Studies have shown that different types of antioxidants, including natural and synthetic antioxidants, can help in disease prevention. The antioxidant compounds may directly react with the reactive radicals to destroy them via accepting or donating electron(s) to directly remove the unpaired status of the radical. Moreover, they may indirectly reduce the production of free radicals by inhibiting the efficacy or expressions of free radical creating enzymes or by stimulating the activities and expressions of other antioxidant enzymes. Thus, it is essential to know the antioxidant mechanisms of action with the free radicals.

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Conflict of interest

The authors declare they have no financial or other conflict of interests related to this chapter.

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Written By

Manal Azat Aziz, Abdulkareem Shehab Diab and Abeer Abdulrazak Mohammed

Submitted: September 21st, 2018Reviewed: December 14th, 2018Published: November 6th, 2019

Figure 1.

Reactive oxygen species (ROS) generation by endogenous and exogenous sources can lead to oxidative damage and accumulation of proteins, lipids and DNA, when defensive (repair) mechanisms of the body become weak. These ROS also modulate the signal transduction pathways, which result in organelle damage, and changes in gene expression followed by altered responses of the cells, which finally results into aging. Adapted from Pandey and Rizvi [5].

2. Oxidative stress

2.1 Oxidative damage to proteins

Protein oxidation can lead to amino acid modification, fragmentation of the peptide chain, aggregation of cross-linked reaction products, and increased electrical charges. Oxidized proteins are more susceptible to proteolysis, and a raise in oxidized proteins may be responsible for the loss of selected physiological and biochemical roles. Free radical damage to proteins may play a role in the causation of cataracts and aging (Figure 2) [1, 6].

Figure 2.

A schematic diagram illustrating the detrimental effects of free radicals on biomolecules. Adapted from Law et al. [1].

2.2 Oxidative damage to lipids

Lipids have an important structural and functional role in cell membranes. After cell death, membrane lipids are susceptible to peroxidation and this process can cause misinterpretation of some lipid peroxidation assays. In particular, polyunsaturated fatty acids are susceptible targets for ROS attack. The important reactive moiety and initiator for ROS chain reaction and lipoperoxidation of polyunsaturated is OH [7]. Because of lipid peroxidation, several compounds are produced, such as alkanes, malondialdehyde, and isoprostanes. These compounds are utilized as indicators in lipid peroxidation assay, and have been confirmed in diseases including neurogenerative diseases, heart disease, and diabetes (Figure 2) [1, 8].

2.3 Oxidative damage to DNA

Activated oxygen and agents that produce oxygen-free radicals, for example, ionizing radiations, promote damage in DNA that leads to deletion, mutations, and other fatal genetic effects. Through this DNA damage, both sugar and base moieties are susceptible to oxidation, leading to base degradation, single-strand breakage, and cross links to proteins. Free radical damage to DNA is associated in the causation of cancer and accelerated aging (Figure 2) [1, 5, 9].

2.4 Oxidative damage to carbohydrates

According to carbohydrates, the production of oxygen-free radicals during early glycation could contribute to glycoxidative damage. Through the primary stages of nonenzymatic glycosylation, fragmentation of sugar forms short-chain species like glycoaldehyde whose chain is too short to cyclize and is thus prone to autoxidation, producing the superoxide radical that can lead to the formation of β-dicarbonyls, which are well-known mutagens [10]. Carbohydrates free radical oxidation mechanisms are comparable to those of lipids. Low molecular carbohydrates, such as glucose, mannitol, and deoxyribose, are well known to interact with HO, forming oxidized intermediates, which does not affect food quality [11].

3. Antioxidants

Antioxidants are inhibitors of oxidation, even at small concentrations; therefore, antioxidants have different physiological functions in the body. In addition, antioxidants act as free radical scavengers, by reacting with the reactive radicals and demolishing them to become less active, less dangerous, and long-lived substance than those radicals that have been neutralized. Antioxidants may be able to neutralize free radicals via accepting or donating electron(s) to remove the unpaired status of the radical [4]. Also, antioxidants can be defined as compounds able to inhibit oxygen-mediated oxidation of different substances from simple molecule to polymer and complicated bio-system [8].

The US Food and Drug Administration (FDA) defined antioxidants as substances utilized to preserve food by retarding deterioration, rancidity, or discoloration owing to oxidation. Whereas antioxidants are important to the food industry to prevent rancidity, antioxidants are also important to biologists and clinicians as they may assist to protect the human body against diseases from ROS danger by regulating ROS-related enzymes [8]. Cellular level of free radicals may be decreased by antioxidants either via inhibiting the activities or expression of free radical generating enzymes such as NAD(P)H oxidase and xanthine oxidase (XO), or by promoting the activities and expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) [12, 13, 14].

Since 1990s, antioxidant research has increased dramatically due to its potential role in disease prevention and health promotion. In biological systems such as animal models and clinical trials, the antioxidant action of pure compounds, foods, and dietary supplements has been extensively examined [4, 15, 16]. Numerous study models have been determined in chemical and/or biological systems to examine the mechanism of action of antioxidants, as well as the identification and recognition of new antioxidants, particularly from natural substances. Further research in animal models and cell cultures has provided critical information on the bioavailability, metabolism, and toxicity issues of antioxidants, suggesting probable clinical applications of these substances. Nevertheless, animal models and human research are expensive and not suitable for early antioxidant screening of foods and dietary supplements. Therefore, cell culture models have been utilized for early screening and study proceeding to animal research and human clinical trials [4].

Antioxidants can protect the cells and organs of the body against the harmful effect of the oxidative stress through various defense mechanisms by both enzymatic and nonenzymatic reactions, which work synergistically and together with each other. To prevent lipid peroxidation in food, nonenzymatic antioxidants are often added. The use of antioxidants for food and therapeutic purposes must be characterized carefully, because several lipid antioxidants can exert a prooxidant effect to other molecules under particular circumstances [5, 7].

The feature of a perfect antioxidant is that it should be readily absorbed, eliminate free radicals, and chelate redox metals at physiologically suitable levels. In addition, it should work in both aqueous and membrane domains, and have a positive effect on gene expression [7].

4. Antioxidant categories

Antioxidants can be classified in several ways [17, 18].

  1. Based on their activity, they can be classified as enzymatic and nonenzymatic antioxidants. Dangerous oxidative products can be converted to H2O2 and then to water by enzymatic antioxidants that are able to break down and get rid of free radicals in a multistep process in the presence of cofactors such as copper (Cu), zinc (Zn), manganese (Mn), selenium (Se), and iron (Fe).

  2. Vitamin C, vitamin E, plant polyphenol, carotenoids, and glutathione are nonenzymatic antioxidants, which act by interrupting free radicals chain reactions.

  3. Based on solubility, antioxidants can be classified as water-soluble or lipid-soluble antioxidants. Vitamin C is a type of water-soluble vitamin found in cellular fluids such as cytosol or cytoplasmic matrix.

  4. According to size, antioxidants can be categorized as small or large-molecule antioxidants. The small molecule antioxidants neutralize the ROS in a process named radicals scavenging and carry them away. Vitamin C, vitamin E, carotenoids, and glutathione (GSH) are the main antioxidants in this category. Large molecule antioxidants include enzymes (SOD, CAT, and GPx) and sacrificial proteins (albumin) that absorb ROS and prevent them from attacking other essential proteins.

  5. Kinetically antioxidants can be categorized as below:

    1. Antioxidants that are able to break chains through reacting with peroxyl radicals containing weak O–H or N–H bonds, phenol, naphthol, hydroquinone, aromatic amines, and aminophenols.

    2. Antioxidants with a capability to break chains by reacting with alkyl radicals: quinines, nitrones, and iminoquinones.

    3. Antioxidants that terminate cyclic chain such as aromatic amines, nitroxyl radicals, and variable valence metal compounds.

    4. Hydroperoxide decomposing antioxidants such as sulfide, phosphide, and thiophosphate.

    5. Metal-deactivating antioxidants include diamines, hydroxyl acids, and bifunctional compounds.

    6. Synergism action of a number of antioxidants including phenol sulfide in which the phenolic group reacts with the peroxylradical’s sulfide group with hydroperoxide.

  6. Based on their occurrence, antioxidants are categorized as natural or synthetic [19, 20].

  1. Natural antioxidants

    They are classified as chain-breaking antioxidants, which react with radicals and convert them into more stable products. Generally, antioxidants of this group are phenolic in structure and include the following:

    1. Antioxidant minerals: these are antioxidant enzymes cofactors like selenium, copper, iron, zinc, and manganese. Absence of the cofactors will definitely enhance many macromolecules metabolism such as carbohydrates.

    2. Antioxidant vitamins: these are important and required for most body metabolism functions such as, vitamin C, E, and B.

    3. Phytochemicals: these are phenolic compounds derivatives that are neither vitamins nor minerals. Examples include flavonoids, catechins, carotenoids, carotene, lycopene, and herbs and spices such as diterpene, rosmariquinone, thyme, nutmeg, clove, black pepper, ginger, garlic, curcumin, and derivatives.

  2. Synthetic antioxidants

    These are phenolic compounds that carry out the role of capturing free radicals and stopping the chain reaction. These compounds include butylated hydroxyl anisole (BHA), butylated hydroxyltoluene (BHT), propyl gallate (PG), metal chelating agent (EDTA), tertiary butyl hydroquinone (TBHQ), and nordihydroguaiaretic acid (NDGA).

4.1 Antioxidant enzymes

There are several enzymes that catalyze reactions to neutralize free radicals and ROS. These enzymes form the body’s endogenous defense mechanisms from free radicals to protect the cell. The enzyme antioxidants GPx, CAT, and SOD are the best-known substances of the antioxidant protection system, and they are responsible for the free radical change [21]. Enzymes are important components of the protection and defense mechanisms, by decreasing ROS generation via removing potential oxidants/transferring ROS/RNS into relatively stable compounds [5]. For optimum catalytic activity, these enzymes require micronutrient cofactors such as Se, Fe, Cu, Zn, and Mn [21].

4.1.1 Superoxide dismutase (SOD)

Irwin Fridovitch of Duke University and Joe McCord discovered antioxidant enzyme (SOD) (EC 1.15.1.1) in 1967, which belongs to the group of oxidoreductases. SOD is an important cellular defense against free radical damage. Therefore, medical scientists have begun to look seriously at free radicals [3]. SOD antioxidant enzymes are metal-containing proteins that catalyze the dismutation of the highly reactive superoxide anion to O2 and to the less reactive species H2O2 (Eq. (1)). The result is that peroxide can be destroyed by reaction of CAT or GPX [22, 23].

O2+O2+2H+SODH2O2+O2E1

In mammals, there are three forms of SOD; the active site of the enzyme contains one or two different atoms of a transition metal in a certain oxidation state. SODs are categorized by their metal cofactors into known forms: cytosolic SOD, extracellular SOD [CuZnSOD], and mitochondrial SOD [MnSOD]. Each form is produced by distinct genes and distinct subcellular localization, but catalyzes the same reaction. This distinct subcellular localization of the three SOD forms is especially significant for compartmentalized redox signaling [24].

CuZnSOD enzymes have two identical subunits of about 32 kDa, though a monomeric structure is found in a high concentration of protein from E. coli. Each subunit includes a metal cluster, an active site, and a Cu and a Zn atom bridged By a histamine residue. The Cu and Zn which are important for SOD enzymatic activity. Zn contributes in appropriate protein folding and stability. Cu is not replaceable with another metal, while Zn is replaceable with cobalt and Cu, and it is not essential for enzyme action at low pH. CuZnSOD plays a major function in the first line of antioxidant defense [25].

MnSOD is a homotetramer 96 kDa; each subunit contains one Mn atom, those cycles from Mn3+ to Mn2+ and back to Mn3+ during the two-step dismutation of superoxide. In mitochondria, the main source of oxygen radicals is the respiratory chain. It was shown that this enzyme is greatly stimulated and decreased by cytokines, while oxidants moderately influenced it [26, 27, 28].

Extracellular SOD (ECSOD) is a tetrameric protein, containing Cu and Zn having a high affinity for certain glycosaminoglycans such as heparin and heparin sulfate [7]. ECSOD is found primarily in the extracellular membrane and to a lesser extent, in the extracellular fluids. It protects against the inactivation of NO liberating from the endothelium by O2¯ through diffusion to smooth muscle, thus preserving endothelial function. Studies have shown that ECSOD plays an essential role in various oxidative stress-dependent pathophysiologies, such as hypertension, ischemia reperfusion injury, and lung injury. In addition, a number of lines of research propose a role for ECSOD in aging. ECSOD plasma levels decrease with aging, and in old rats, gene transfer of ECSOD improves endothelial function. However, it is still unknown whether ECSOD expression or activity in blood vessels is adjusted by aging and whether endogenous ECSOD is engaged in regulation of vascular functions during aging [29].

4.1.1.1 Application

SOD enzymes enhance the rejuvenation and cellular repair, while decreasing the damage caused by free radicals. SOD is necessary to generate sufficient amounts of skin building cells named fibroblasts and plays an essential role in preventing the progress of amyotrophic lateral sclerosis (ALS), which causes death if it affects the nerve cells in the spinal cord and brain. In addition, this enzyme is also utilized for inflammatory diseases treatment, burn injuries, prostate problems, corneal ulcer, arthritis, and reversing the long-term consequences of radiation and smoke exposure. Furthermore, it prevents wrinkle formation if the skin lotion contains this enzyme. Also, it enhances wound healing, reduces scars, and lightens skin pigmentation caused by UV rays.

Moreover, SOD facilitates nitric oxide moving into hair follicles. This is beneficial for people with a genetic predisposition or free radicals for premature hair loss. SOD is a very potent antioxidant, in that it combats the effect of free radicals on the hair follicles. Because of nitric oxide’s ability as a blood vessel relaxant, allowing more blood to reach the hair follicle, and SOD ability to remove free radicals, hair loss can be prevented or reversed. Maintaining overall well-being and health, as well as free radical protection, can be achieved by taking dietary supplement that provides an adequate supply of SOD [3].

4.1.2 Catalase (CAT)

Catalase (EC 1.11.1.6) is an enzyme responsible for H2O2 degradation that is generated by oxidases involved in β-oxidation of fatty acids, respiration, and purine catabolism [3]. It is present in nearly all animal cells as a protective enzyme. The highest levels of CAT activity are measured in the liver, kidney, and red blood cells.

Human CAT composes four identical subunits of 62 kDa, each subunit containing four distinct domains and one prosthetic heme group, and has a molecular mass of about 240 kDa [30]. CAT enzyme reacts with H2O2 to form water and molecular oxygen and with H donors such as methanol, ethanol, formic acid, or phenols with peroxidase activity. CAT protects cells from H2O2 generated within them. Therefore, it has an essential role in the acquisition of tolerance to oxidative stress in the adaptive response of cells. Various disease conditions and abnormalities are associated with the deficiency or mutation of CAT enzyme [30, 31].

4.1.2.1 Application

In the food industry, CAT enzyme is used to remove H2O2 from milk prior to cheese production, and to prevent food from oxidizing in food wrappers. In addition, CAT enzyme is used in the textile industry for H2O2 removal from fabrics, to make sure the material is peroxide free. Recently, esthetics industries have begun to use CAT enzyme in facial masks, as the combination of CAT enzyme with H2O2 on the face can be used to increase cellular oxygenation in the upper layers of the epidermis [3].

4.1.3 Glutathione perioxidases (GPx)

Glutathione peroxidase (EC 1.11.1.9) contains a single selenocysteine residue in each of the four identical subunits, which is important for enzyme activity. GPx (80 kDa) is an imperative intracellular enzyme that catalyzes H2O2 to water and lipid peroxides to their corresponding alcohols mainly in the mitochondria and sometimes in the cytosol. In mammals, there are five GPx isoenzymes. Though their expression is ubiquitous, the level of each isoform differs depending on their tissue type. Mitochondrial and cytosolic glutathione peroxidase (GPx1 or cGPx) reduces fatty acid hydroperoxides and H2O2 at the expense of glutathione [32].

GPx1 is the main ubiquitous selenoperoxidase present in most cells; found in the cytosolic, mitochondrial, and peroxisomal compartments. It is an important antioxidant enzyme required in the detoxification of H2O2 and lipid hydroperoxides and preventing DNA, protein and lipids damage by harmful accumulation of intracellular H2O2 [33]. GPx1 uses GHS as an obligate co-substrate in the reduction of H2O2 to water [32]. Phospholipid hydroperoxidase glutathione (PHGPX) is found in most tissues and can directly reduce the phospholipid hydroperoxides, fatty acid hydroperoxides, and cholesterol hydroperoxides that are produced in peroxidized membranes and oxidized lipoproteins [30].

GPx4 is found in both the cytosol and the membrane fraction, and is highly expressed in renal epithelial cells and tests. Cytosolic GPx2 or extracellular GPx3 is inadequately found in nearly all tissues except for the gastrointestinal tract and kidney. In recent, GPx5, a new kind, expressed particularly in mouse epididymis, is selenium independent [34].

Several studies underlined the clinical importance of GPx. In addition, GPx, especially GPx1, have been implicated in the progression and prevention of many frequent and complex diseases, including cancer and cardiovascular disease [34, 35].

4.1.3.1 Application

GPx is an important antioxidant enzyme in the body. Glutathione (GHS), the master antioxidant, is important for GPx levels due to the closely linked relationship; GHS is a tripeptide that protects the cells against the negative effects of pollution and functions as the body’s immune system booster. GHS plays an essential role in red blood cells to remain intact and protects white blood cells, which are responsible for the immune system. An antioxidant’s role is specifically essential for the brain because it is sensitive to the presence of free radicals. To increase the body’s protection from free radicals, it is imperative to combine certain antioxidants such as glutathione, vitamin C and E, Se, and GPx [3].

4.2 Nonenzymatic antioxidants

In previous decades, there has been increasing evidence that large amounts of antioxidants present in our diet contribute to the antioxidant defense system by preventing oxidative stress and specific human diseases. Phytochemicals, the plant-derived compounds, are one of the classes of the dietary factors, which play an essential role in functions of the body. Food materials contain a number of natural compounds reported to have antioxidant characteristics due to the presence of hydroxyl groups in their structure. Synthetic and natural antioxidants prevent the oxidative damage to the most important macromolecules such as lipids, proteins, and nucleic acids found in human body through scavenging the free radicals formed in different biochemical processes [36]. These antioxidants consist of small molecules including vitamin C, E, and β-carotene or natural antioxidants such as flavonoids, tannins, coumarins, phenolics, and terpenoids [37]. Because of oxidative stress, the free radicals that have been produced react with lipids, proteins and nucleic acids and lead to stimulation of apoptosis, which causes various neurological, cardiovascular, and physiological disorders [38].

In addition to phytochemical antioxidants, which can protect the body from oxidative damage, there are other antioxidants for example polyphenols, lycopene, and lutein [39]. Even though there has been a considerable concentration on antioxidant function of phytochemicals for several years, it is distinguished that phytochemicals have nonantioxidant effects important for health such as cell signaling and gene expression [40].

4.2.1 Glutathione

Glutathione (γ-glutamyl-cysteinyl-glycine; GSH) is a tripeptide and is the most abundant intracellular antioxidant protecting normal cells from oxidative injury due to its role as a substrate of ROS scavenging enzymes. Glutathione is primarily present in its reduced form (GSH) in normal conditions, with only a small amount being found in the fully oxidized state (GSSG) [41]. Glutathione functions as a nonenzymatic antioxidant through free radical scavenging in cells and serves as a cofactor for several enzymes, include GPx, glutathione reductase (GR), and glutathione transferase (GST) [42, 43].

4.2.1.1 Application

Recently, there is a new era of therapeutic applications of glutathione through the association of decreased GSH levels with the common features of aging and a wide range of pathological conditions, including neurodegenerative disorders. Remarkably, depletion and alterations of GSH in its metabolism appear to be crucial in the onset of Parkinson’s disease [44].

4.2.2 Vitamin E

Vitamin E, C, and β-carotene are the main antioxidant vitamins for tissues against free radical damage. Vitamin E, a major lipid soluble antioxidant, functions as the most important membrane-bound antioxidant, neutralizing free radicals, and preventing oxidation of lipids within membranes [45]. Vitamin E is the free radical scavenger in the prevention of chronic diseases [46]. α-Tocopherol is the main form of vitamin E with antioxidant and immune functions. α-tocopherol has been revealed to be a more effective inhibitor of peroxynitrite-induced lipid peroxidation and inflammatory reactions [47]. In vitro tocotrienols have excellent antioxidant activity and have been proposed to restrain ROS more effectively than tocopherols [48].

4.2.2.1 Application

The main function of vitamin E is to protect against lipid peroxidation through evidence suggesting that α-tocopherol and vitamin C function together in a cyclic type of process. It has been reported that vitamin E supplementation in hypercholesterolemic patients has shown to increase autoantibody levels against oxidized LDL, and prevent ischemic heart disease [49].

4.2.3 Vitamin C

In extracellular fluids, vitamin C, a water-soluble vitamin, is the most important antioxidant and can protect biomembranes against lipid peroxidation injury through eliminating peroxyl radicals in the aqueous phase before peroxidation initiation. Vitamin C is an effective antioxidant located in the aqueous phase of cells; it simply loses electrons to give stability to reactive species such as ROS [45]. In addition to vitamin C’s biological functions as a superoxide and hydroxyl radicals’ scavenger, it also functions as an enzyme cofactor [42].

4.2.3.1 Application

Vitamin C plays an essential function in the defense against oxidative damage particularly in leukocytes, as well as the possible effect it may have on the treatment of chronic degenerative diseases, autoimmune diseases, and cancer [42, 45].

4.2.4 Carotenoids

Carotenoids are structurally and functionally different natural pigments found in many fruits and vegetables. A combination of carotenoids and tocopherols antioxidants in the lipid phase of biological membranes may enhance better antioxidant protection than tocopherols alone. Antioxidant characteristics of carotenoids include scavenging single oxygen and peroxyl radicals, thiyl, sulfonyl, sulfur, and NO2 radicals and giving protection to lipids from superoxide and hydroxyl radical attack [49].

4.2.4.1 Application

Carotenoids and some of their metabolites are proposed to play a protective function in several ROS-mediated disorders, include cardiovascular, cancer, and myocardial infarction among smokers. Carotenoid-rich food and supplementation decrease morbidity in nonsmokers and reduce the risk of prostate cancer [42].

4.2.5 Vitamin A

Vitamin A, a lipid soluble vitamin, is important for human health and has free radicals scavenging features that aid it to act as a physiological antioxidant in protecting a number of chronic diseases such as cardiovascular disease and cancer. All transretinol, the parent compound, are the most abundant dietary form of vitamin A that occurs naturally in the form of fatty acid esters such as retinyl palmitate, while retinal and retinoic acid are the minor natural dietary components of vitamin A [45]. Vitamin A was first labeled as an inhibitor of the effect of linoleic acid on the oxidation processes. At present, vitamin A and carotenoids are known for their antioxidant actions depending on their capability to interact with radicals and prohibit cell lipid peroxidation [9].

4.2.5.1 Application

Vitamin A is important for life in mammals; it cannot be synthesized in body and has to be supplied by food. Due to its role as antioxidant, vitamin A has a new role in preventive nutrition against neurodegenerative diseases. Recently, vitamin A has increased the interest in supplementation via food [50].

4.2.6 Uric acid

Uric acid, hyperuricemia, is a potent free radical scavenger and estimated ~60% of free radical scavenging capacity in plasma [51]. Uric acid is a physiological antioxidant and an effective preventer of the production of ROS species during the action of xanthine oxidase (XO) in catalysis reaction of xanthine and hypoxanthine [42]. A study illustrated the urate ability to scavenge oxygen radicals and protect the erythrocyte membrane from lipid oxidation, characterized further by Ames et al. through the effect of uric acid in protection of cells from oxidants, which related to a variety of physiological situation [51]. Nevertheless, it is probable that the increase in serum level of uric acid is a response to protect against the detrimental effects of extreme free radicals and oxidative stress [52].

4.2.6.1 Application

Studies showed that serum uric acid levels are highly predictive of mortality in patients with coronary artery disease, heart failure, or diabetes. In addition, high uric acid level is associated with deleterious effect on vascular function. Recently, it has been found that patients with high serum uric acid level had impaired flow-mediated dilation, which was normalized by therapy for 3 months with the xo inhibitor allopurinol [53].

4.2.7 Lipoic acid

Lipoic acid is a strong antioxidant, and it reveals a great capability of antioxidant when given natural or as a synthetic drug. Lipoic acid is a short-chain fatty acid, composed of sulfur in their structure that is known for its contribution in the reaction that catalyzes the oxidation decarboxylation of α-keto acids, for example pyruvate and α-ketoglutarate, in the citric acid cycle. Lipoic acid and its reduced form, dihydrolipoic acid (DHLA), are capable of quenching free radicals in both lipid and aqueous domains. Lipoic acid and DHLA have been revealed to have antioxidant, cardiovascular, antiaging, detoxifying, anti-inflammatory, anticancer, and neuroprotective pharmacological properties [40, 54].

4.2.7.1 Application

Regarding the pathology of diabetes, there are many potential applications for lipoic acid. In type I diabetes, destruction of pancreatic β-cells leads to loss secretion of insulin, while the major problem in type II diabetes is insulin resistance of peripheral tissues. Lipoic acid has potential preventive or ameliorative effect in both type I and type II diabetes [54].

4.2.8 Flavonoids

Flavonoids are low in molecular weight and are the main type of phenolic compounds in plants. They are structured by 15 carbon atoms, organized in a C6-C3-C6 configuration. Due to their high redox potential, flavonoids are, in particular, important antioxidants that allow them to function as reducing agents, hydrogen donors, and singlet oxygen quenchers. In addition, they include a metal chelating potential [55].

4.2.8.1 Application

Flavonoids are generally found in many fruits and vegetables. When human increasingly consumed it, flavonoids have been linked with a decrease in the incidence of diseases such as prostate [56, 57] or breast cancer [58, 59].

4.2.9 Tannins

Tannins are relatively high-molecular compounds, which comprise the third essential group of phenolics and can be divided into condensed and hydrolysable tannins. Condensed tannins are produced by the polymerization of flavonoid units. The mainly studied condensed tannins are based on flavan-3-ols: (−)-epicatechin and (+)-catechin. Hydrolysable tannins are heterogeneous polymers containing phenolic acids, in particular, gallic acid (3,4,5 trihydroxyl benzoic acid) and simple sugar [42, 55].

4.2.9.1 Application

Because of tannin features, such as being the potential metal ion chelators, protein-precipitating agents, and biological antioxidants, tannins have different effects on biological systems. As a consequence of the diverse tannins biological roles and structural variation, it has been difficult to modify models that would let a precise prediction of their effects in any system. Therefore, the tannin structure modification and activity relationship are important to predict their biological effect [42].

5. Antioxidants: mechanisms of action

Generally, the antioxidants defend against free-radicals-induced oxidative damage by various mechanisms as discussed in below sections.

5.1 Preventive antioxidants

ROS such as H2O2, O2, and OH are produced irreversibly during metabolism. Therefore, methods have been extensively studied to reduce the damage enhanced by oxidative stress. Intracellular antioxidant enzymes produced in the cell are an essential protective mechanism against free radicals formation. SOD, CAT, GPx, GR, GST, thioredoxin reductase, and hemeoxygenase are the most important antioxidants enzymes. SODs convert O2 into H2O2, which is then converted into water by CAT, GPx, and Fenton reaction. Thus, two toxic species are converted into a harmless product (Figure 3) [5].

Figure 3.

Antioxidant enzyme system, O2, is dismutaed toH2O2 by SOD enzyme. The resulted H2O2 is converted into water by CAT and GPx. In this way, two toxic species, O2 and H2O2, are converted into the harmless product water. GPx neutralized H2O2 via taking hydrogen from two GSH molecules forming two molecules of water and GSSG. GR then regenerates GSH from GSSG. CAT, the essential part of enzymatic defense, neutralizes H2O2 into water. By Fenton reaction, H2O2 is also converted to the highly reactive OH and then to water through oxidation of Fe2+ to Fe3+. Adapted from Pandey and Rizvi [5].

During metabolism, peroxides are formed and then eliminated via both GST and GPX. GRd regulates the equivalent of GSH and oxidized glutathione (GSSG), and the ratio of GSH/GSSG is a known index of oxidative stress [60]. The action of GRd plays an imperative role in increasing GSH concentration, which maintains the oxido-redox condition in the organism [14]. Consequently, the oxidative stress role has been reported in the progress and clinical symptom of autism. Recently, a comparison study between autism and control individuals showed decrease in GSH/GSSG ratio and increase in free radical generation in autism compared to control cells [60]. In addition, GPx is presented throughout the cell, while CAT is frequently limited to peroxisomes. In the brain, which is very sensitive to free radical damage, it has seven times more GPx activity than CAT activity. Moreover, CAT’s highest levels are found in the liver, kidney, and erythrocytes, where it decomposes the most of H2O2 [61].

5.2 Free radical scavengers

5.2.1 Scavenging superoxide and other ROS

Superoxide (O2•¯), a predominant cellular free radical, is contributed in a huge number of deleterious alterations often linked to a low concentration of antioxidants and associated with a raise in peroxidative processes. Though O2•¯ itself is not reactive to biomolecules, it assists in production of stronger OH•, and ONOO¯.O2•¯ is formed in large quantities, in phagocytes via NADPH oxidase enzyme during pathogen-killing process. In addition, it is a byproduct of mitochondrial respiration [3].

5.2.2 Scavenging hydroxyl radical and other ROS

Hydroxyl radical (OH) is an extremely active and more toxic radical on biologic molecules such as DNA, lipids, and proteins than other radical species. In general, OH is considered to be formed from the Fe2+ or Cu+/H2O2 Fenton reaction system, through incubation FeSO4 and H2O2 in aqueous solution. Therefore, antioxidants activity as OH scavenger can be accomplished by direct scavenging or prohibiting of OH generation by the chelation of free metal ions or altering H2O2 to other nontoxic compounds [3].

5.2.3 Metal ion (Fe2+, Fe 3+, Cu2+, and Cu+) chelating

Even though trace minerals are essential dietary components, they can function as prooxidants (through enhancing formation of free radicals). Fe2+ and Cu+ react with H2O2, which is a product produced by the dismutation of the O2•¯ via SOD, to form extremely reactive OH (Eq. (2)). Dissimilarly, iron and copper’s reaction with H2O2 forms more singlet oxygen than OH. Fe2+ and Cu+ are oxidized to Fe3+ and Cu2+, respectively. Cellular reductant such as NADH and oxidized metal ions Fe3+, and Cu2+ are reduced and permit the recycling to react with another molecule of H2O2 to produce OH radical in the presence of vitamin C (Eq. (3)). OH is strongly reactive and can directly react with proteins and lipids to produce carbonyls (aldehydes and ketones), cross linking, and lipid peroxidation. Chelating metal ions are able to decrease their action, thus reducing the ROS formation.

Fe2+orCu++H2O2Fe3+orCu2++OH+OHE2
Fe3+orCu2++vitCHFe2+orCu++vitaminC+H+E3

Studies showed that Se antioxidant is able to chelate Cu+ (formed in situ with Cu2+/ascorbic acid) extremely efficiently and prevent the damage of DNA by OH radical (formed via Cu+/H2O2) [3].

5.3 Free radical generating enzyme inhibitors

It has been reported that the main sources of free radicals in different physiological and pathological conditions is associated with a number of enzymes. NADPH oxidases are a type of plasma membrane linked enzymes that have an ability to transfer one electron from the cytosolic donor NADPH to a molecule of extracellular oxygen, forming O2•¯ [62]. Uric acid is formed by xanthin oxidase enzyme through catalyzing the oxidation of hypoxanthine and xanthin to uric acid yielding O2•¯ and H2O2 and increase the oxidation level in an organism [63]. In addition, O2•¯ is also formed as a by-product of mitochondrial respiration as well as several other enzymes, for example NADH oxidase, monooxygenases and cyclooxygenases. O2•¯ is biologically quite toxic and is produced in significant amounts by the enzyme NADPH oxidase to be used in oxygen dependent killing mechanisms for invading pathogens. During the respiratory burst, it is an important control of reactive oxygen derivatives production for the defense of an organism against invading microorganisms, without causing an important loss of tissue functions [3]. Nonetheless, excessive ROS enhance oxidative stress such as low density lipoprotein (LDL) oxidation. A direct link between elevated phagocytic NADPH oxidase activities and increased circulating oxidized LDL in metabolic syndrome patients has been found. As a result, both modulation of NADPH oxidase to prohibit ROS overproduction and antioxidants supplementation have been reported as active strategies to prevent the deleterious effect of oxidative stress in hemodialysis patients [64]. In recent years, many natural antioxidants have revealed potential to inhibit enzymes that promote O2•¯ generation as well as the development of new therapeutic agents for oxidative stress-related diseases [3].

5.4 Prevention of lipid peroxidation

Lipid peroxidation is defined as oxidative deterioration of lipids composed of C-C double bonds such as unsaturated fatty acids, glycolipids, cholesterol, cholesterol ester, phospholipids. ROS damage the unsaturated fatty acids, which include numerous double bonds and the methylene-CH2-groups with particularly reactive hydrogen atoms, and begin the radical peroxidation chain reactions [65]. Antioxidants are able to directly react and quench peroxide radicals to stop the chain reaction. Lipid peroxidation and DNA damage are related to different chronic diseases, such as cancer, and atherosclerosis. Antioxidants can scavenge ROS and peroxide radicals, therefore prohibiting or treating certain pathogenic situations. Scientific attention has been concentrated in lipid peroxidation for recognizing natural antioxidants and studying their mechanism of action. Researches on antioxidants such as vitamins, polyphenols and flavones against free radical enhanced lipid peroxidation have been assumed in many systems such as lipid, red blood cells and LDL. The antioxidant activity of these polyphenols depends considerably on molecules structure, the initiation conditions and the microenvironment of the reaction medium [3].

5.5 Prevention of DNA damage

In vivo, the OH and ONOO¯ radicals produced from nitric oxide and O2•¯ are able to react directly with plasmid DNA macromolecules to cleave one DNA strand, leading to oxidative DNA damage. Cell death and mutation as a result of DNA damage are associated with neurodegenerative and heart diseases, cancer and aging. Consequently, DNA or plasmid damage has received attention and been utilized as models for the study and identification of antioxidants [66]. A study has been progressed include DNA damage caused by Cu+ induced OH, through metal-free plasmid DNA mixed with Cu2+, ascorbic acid and H2O2 at pH 7. The reaction includes reduction of Cu2+ to Cu+ in situ with ascorbic acid. The OH radical formed via Cu+/H2O2 cleaves one DNA strand, causing the ordinarily supercoiled plasmid DNA to unwind [3].

5.6 Prevention of protein modification

Besides lipid peroxidation and DNA damage, protein modification through nitration or chloration of amino acids also is caused by ROS. In vivo, peroxynitrite, O═N─O─O¯, is a powerful oxidant and nitrating agent formed through the reaction of O2•¯ with free radical nitric oxide via a diffusion-controlled reaction. In cells, ONOO¯ is a much stronger oxidizing agent than O2•¯ and is able to damage a wide range of different molecules such as DNA and proteins. ONOO¯ and its protonated form peroxynitrous acids (ONOOH) are capable of exerting direct oxidative modifications during one or two electron oxidation processes [67]. In vivo, ONOO¯ reacts nucleophically with CO2 to produce nitrosoperoxy carbonate, which is the predominant pathway for ONOO¯. These modifications often cause the alteration of protein function or structure, in addition to enzyme activities inhibition. Proteins containing nitrotyrosine residues have been detected in various pathogenic conditions, such as diabetes, hypertension, and atherosclerosis, all linked with promoted oxidative stress, including increased formation of ONOO¯. Antioxidants and antioxidant enzyme are utilized to prevent the protein modification of ONOO¯. Antioxidants or enzyme such as CAT is able to remove H2O2 and also inhibit HOCl formation; similarly, SOD or antioxidants, like polyphenols, may scavenge O2•¯ and inhibit ONOO¯ formation [3].

6. Conclusion

This chapter briefly summarized types of antioxidants, and their mode of action. The harmful products formed during normal cellular functions are oxygen radical derivatives that are the most important free radical in the biological system. For normal physiological functioning, it is important to maintain a tolerated antioxidant status by increasing intake of natural antioxidants. Studies have shown that different types of antioxidants, including natural and synthetic antioxidants, can help in disease prevention. The antioxidant compounds may directly react with the reactive radicals to destroy them via accepting or donating electron(s) to directly remove the unpaired status of the radical. Moreover, they may indirectly reduce the production of free radicals by inhibiting the efficacy or expressions of free radical creating enzymes or by stimulating the activities and expressions of other antioxidant enzymes. Thus, it is essential to know the antioxidant mechanisms of action with the free radicals.

Conflict of interest

The authors declare they have no financial or other conflict of interests related to this chapter.

\n',keywords:"oxidative stress, antioxidants, reactive oxygen species, antioxidant enzymes, free radicals, antioxidant mechanisms",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65225.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65225.xml",downloadPdfUrl:"/chapter/pdf-download/65225",previewPdfUrl:"/chapter/pdf-preview/65225",totalDownloads:2154,totalViews:0,totalCrossrefCites:3,totalDimensionsCites:15,totalAltmetricsMentions:0,impactScore:11,impactScorePercentile:98,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"September 21st 2018",dateReviewed:"December 14th 2018",datePrePublished:null,datePublished:"November 6th 2019",dateFinished:"January 18th 2019",readingETA:"0",abstract:"Oxidative stress has received a considerable scientific attention as a mediator in the etiology of many human diseases. Oxidative stress is the result of an imbalance between free radicals and antioxidants. Cells can be damaged by free radicals that are considered to play a main role in the aging process and diseases development. Antioxidants are the first line of defense against the detrimental effects of free radical damage, and it is essential to maintain optimal health via different mechanisms of action. Types of antioxidants range from those generated endogenously by the body cells, to exogenous agents such as dietary supplements. Antioxidant insufficiency can be developed as a result of decreased antioxidant intake, synthesis of endogenous enzymes, or increased antioxidant utilization. To maintain optimal body function, antioxidant supplementation has become an increasingly popular practice through improving free radical protection. In this chapter, we first elucidate the oxidative stress, and then define the antioxidant and its categories. Finally, introduce the antioxidants mode of actions for cell protection from free radicals.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65225",risUrl:"/chapter/ris/65225",book:{id:"8008",slug:"antioxidants"},signatures:"Manal Azat Aziz, Abdulkareem Shehab Diab and Abeer Abdulrazak Mohammed",authors:[{id:"276717",title:"Associate Prof.",name:"Manal",middleName:null,surname:"Azat Aziz",fullName:"Manal Azat Aziz",slug:"manal-azat-aziz",email:"manalbazaz@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"286369",title:"Dr.",name:"Abdulkareem",middleName:null,surname:"Shehab Diab",fullName:"Abdulkareem Shehab Diab",slug:"abdulkareem-shehab-diab",email:"dr.kariem2006@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"312155",title:"Dr.",name:"Abeer Abdulrazak",middleName:null,surname:"Mohammed",fullName:"Abeer Abdulrazak Mohammed",slug:"abeer-abdulrazak-mohammed",email:"abemoh777@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Oxidative stress",level:"1"},{id:"sec_2_2",title:"2.1 Oxidative damage to proteins",level:"2"},{id:"sec_3_2",title:"2.2 Oxidative damage to lipids",level:"2"},{id:"sec_4_2",title:"2.3 Oxidative damage to DNA",level:"2"},{id:"sec_5_2",title:"2.4 Oxidative damage to carbohydrates",level:"2"},{id:"sec_7",title:"3. Antioxidants",level:"1"},{id:"sec_8",title:"4. Antioxidant categories",level:"1"},{id:"sec_8_2",title:"4.1 Antioxidant enzymes",level:"2"},{id:"sec_8_3",title:"4.1.1 Superoxide dismutase (SOD)",level:"3"},{id:"sec_8_4",title:"4.1.1.1 Application",level:"4"},{id:"sec_10_3",title:"4.1.2 Catalase (CAT)",level:"3"},{id:"sec_10_4",title:"4.1.2.1 Application",level:"4"},{id:"sec_12_3",title:"4.1.3 Glutathione perioxidases (GPx)",level:"3"},{id:"sec_12_4",title:"4.1.3.1 Application",level:"4"},{id:"sec_15_2",title:"4.2 Nonenzymatic antioxidants",level:"2"},{id:"sec_15_3",title:"4.2.1 Glutathione",level:"3"},{id:"sec_15_4",title:"4.2.1.1 Application",level:"4"},{id:"sec_17_3",title:"4.2.2 Vitamin E",level:"3"},{id:"sec_17_4",title:"4.2.2.1 Application",level:"4"},{id:"sec_19_3",title:"4.2.3 Vitamin C",level:"3"},{id:"sec_19_4",title:"4.2.3.1 Application",level:"4"},{id:"sec_21_3",title:"4.2.4 Carotenoids",level:"3"},{id:"sec_21_4",title:"4.2.4.1 Application",level:"4"},{id:"sec_23_3",title:"4.2.5 Vitamin A",level:"3"},{id:"sec_23_4",title:"4.2.5.1 Application",level:"4"},{id:"sec_25_3",title:"4.2.6 Uric acid",level:"3"},{id:"sec_25_4",title:"4.2.6.1 Application",level:"4"},{id:"sec_27_3",title:"4.2.7 Lipoic acid",level:"3"},{id:"sec_27_4",title:"4.2.7.1 Application",level:"4"},{id:"sec_29_3",title:"4.2.8 Flavonoids",level:"3"},{id:"sec_29_4",title:"4.2.8.1 Application",level:"4"},{id:"sec_31_3",title:"4.2.9 Tannins",level:"3"},{id:"sec_31_4",title:"4.2.9.1 Application",level:"4"},{id:"sec_35",title:"5. 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Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk. The American Journal of Cardiology. 2004;94:93293-93295'},{id:"B54",body:'Packer L, Witt EH, Tritschler HJ. Alpha lipoic acid as a biological antioxidant. Free Radical Biology and Medicine. 1995;19(2):227-250'},{id:"B55",body:'Walter M, Marchesan E. Phenolic compounds and antioxidant activity of rice. Brazilizn Archives of Biology and Technology. 2011;54(1):371-377'},{id:"B56",body:'Tsao R, Yang R. Optimization of a new mobile phase to know the complex and real polyphenolic composition: Towards a total phenolic index using high performance liquid chromatography. Journal of Chromatography. 2003;1018(1):29-40'},{id:"B57",body:'Jaganathan SK et al. Role of pomegranate and citrus fruit juices in colon cancer prevention. World Journal Gastroenterology. 2014;20(16):4618-4625'},{id:"B58",body:'Sharmila G et al. Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clinical Nutrition (Edinburgh, Scotland). 2014;33(4):718-726'},{id:"B59",body:'Yiannakopoulou EC. Effect of green tea catechins on breast carcinogenesis: A systematic review of in-vitro and in-vivo experimental studies. European Journal of Cancer Prevention: The official Journal of the European Cancer Prevention Organisation. 2014;23(2):84-89'},{id:"B60",body:'James SJ, Rose S, Melnyk S, et al. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. Federation of American Societies For Experimental Biology Journal. 2009;23:237-283'},{id:"B61",body:'Marklund SL, Westman NG, Lundgren E, et al. Copper and zinc containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Research. 1982;42:1955-1961'},{id:"B62",body:'Lin HC, Tsal SH, Chen CS, et al. Structure-activity relationship of coumarin derivatives on xanthine oxidase-inhibiting and free radical-scavenging activities. Biocmeical Pharmacology. 2008;75:1416-1425'},{id:"B63",body:'Schroder K, Vecchione C, Jung O, et al. Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet. Free Radical Biology and Medicine. 2006;41:1353-1360'},{id:"B64",body:'Castilla P, Davalos A, Teruel JL, et al. Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients. American Journal of Clinical Nutrition. 2008;87:1053-1561'},{id:"B65",body:'Porter NA, Caldwell SE, Mills KA. Mechanisms of free radical oxidation of unsaturated lipids. Lipids. 1995;30:277-290'},{id:"B66",body:'Zhao F, Tang YZ, Liu ZQ. Protective effect of icariin on DNA against induced oxidative damage. Journal of Pharmacy and Pharmacology. 2007;59:1729-1732'},{id:"B67",body:'Pacher P, Beckman JB, Liaudet L. Nitric oxide and peroxynitrite in health and disease. 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1. Introduction

Mg-alloys are being considered as one of the most versatile material choices among the structural materials that exhibit both energy efficiency and environmental benefits. Mg-based materials (alloys and composites) have enormous and unlimited potential to replace aluminum, steel, and structural plastics in diverse industrial and commercial sectors such as automotive, aviation, defense, biomedical, sporting equipment, consumer electronics, etc. These applications result from the need to use magnesium and its alloys as a material with favorable physical properties, especially high relative strength (Rm/ρ). Due to the good casting properties of magnesium, it was used primarily in cast structural elements. Wrought alloys have been used on a smaller scale so far, but material research and plastic formability processes to produce semi-finished products from magnesium alloys are currently under intensive development. The development is caused by the possibility of using various types of light structures in the construction, including vehicles made of magnesium-based materials, for which, for example, thin sheets are the basic initial material. This is mainly due to the attempt to reduce the weight of the structure and ensure adequate strength.

The interest in magnesium alloys for various structural elements, e.g., for the aviation industry, dates back to the 1940s. Examples of applications concerned, for example, the Northrop XP-56 plane, in which virtually all parts exposed to elevated temperature were made of magnesium and its alloys [1], B-36 bomber or [2], the S55 helicopter by Westland Aircraft Ltd. (1950 r.) [1, 3].

In later years, the use of magnesium alloys for aircraft structural elements was significantly limited, which was mainly due to the rapid corrosion of alloys (the main disadvantage), opinions about the flammability of magnesium, low metallurgical purity, low strength, high processing costs through plastic formability and poor machinability [4, 5, 6, 7].

Since the beginning of the twenty-first century, there has been a renewed, significant increase in interest in magnesium alloys for applications in the aerospace industry. It results from the development of new coatings that can protect alloys against corrosion, new alloys, new technologies of obtaining semi-finished products by casting methods, and the improvement of various plastic forming technologies, which significantly improves the properties of the product and allows the use of these alloys wherever engineers look for very light construction elements, relatively durable and with anticorrosion protection at the same time [8, 9, 10].

The main problem in the development of techniques for processing magnesium alloys with metal forming methods is low formability [4, 11]. Low deformability at room temperature as well as temperature increased to 200°C of magnesium alloys result from a limited number of hexagonal lattice slip systems. The test results show that the microstructure of Al-Mg-Zn alloys deformed at temperatures up to 200°C shows bands slip and deformation twins [11]. In the range from 200 to 300°C, limited dynamic recovery and the formation of nuclei of dynamic recrystallization are observed. Continuous dynamic recrystallization takes place above 300°C, which results in an almost twofold increase in formability.

Metal forming of magnesium and its alloys is carried out, depending on the content of alloying elements, only in a narrow temperature range. Grains with an average diameter of up to 10 μm were obtained in magnesium alloys by thermo-plastic treatment. The fragmentation of the grains below 10 μm is only achieved by introducing large deformations. The use of unconventional methods of deformation allows for obtaining the grinding of magnesium alloys to sub-micrometric or nanometric sizes. Therefore, these deformation methods constitute a very significant support for conventional forming methods [12, 13, 14].

In magnesium alloys, deformation processes are carried out at an elevated temperature. Therefore, it is practically impossible to obtain nanometric grain sizes obtained by the development of shear bands. The most common methods of large deformation, leading to the grinding of the grains of magnesium alloys, are equal channel angular pressing (ECAP) [15, 16] or hydrostatic extrusion [14, 17].

Basic magnesium alloys for metal forming contain up to 8% Al and the addition of Mn (up to 2%), Zn (usually up to 1.5%), Si (about 0.1%), and traces of Cu, Ni, Fe. There are three basic groups of magnesium alloys for metal forming. The first group includes mainly alloys with the addition of aluminum, zinc, and manganese. The second group includes alloys containing mainly the elements Zn, RE, Y, Zr, Th, and the third group, which is in the phase of intensive research, consists of new ultralight alloys containing lithium.

Magnesium alloys for metal forming are still used to a relatively small extent, which results from technological difficulties in metal forming and high production costs [13, 18, 19]. The main disadvantage of magnesium and its alloys is low deformability at ambient temperature, which results from the type of crystal lattice. At ambient temperature, only one in-plane glide system (0001) is active. In addition to low temperature slip, a significant amount of twinning is observed in magnesium alloys.

Hot forming of magnesium alloys, depending on the chemical composition and deformability, is performed using the following methods [20, 21]:

The formability effect of magnesium alloys has been recently also used in a relatively new solid-state joining process, under the influence of frictional heat, i.e., Friction Stir Welding (FSW). There is no melting involved in the process unlike conventional Fusion welding processes. This method gives very good results in the creation of strong joints, competitive to other joining techniques that require additional joining materials (e.g., riveting, bolted connections, welding, and others). Joining elements (e.g., sheets) made of magnesium alloys with this technique are very effective and require careful selection of process parameters, taking into account the special features of the plasticization of magnesium alloys and the stirring effect in the joint area [4, 22, 23, 24].

2. Evaluation of plastic formability of Mg alloys

Various magnesium alloys for plastic deformation have difficulties in carrying out metal forming processes. The evaluation of the plastic formability of magnesium alloys can be conducted by determining the mechanical behavior of samples of tested materials in compression, torsion, and tensile tests. These tests reflect relatively well essential features of the state of stress or deformation in technological processes of metal forming, including extrusion, forging, and rolling, respectively.

To evaluate mechanical behavior of the material in extrusion process, the upsetting test was used to realize plastic deformation under various conditions and to look for adequate their choice for real deformation process. The grades AZ31, AZ61, AZ80, WE43, and magnesium alloys with lithium, as casted ingots and extruded preforms, were used in the research work. In order to study feasibility of these magnesium alloys in extrusion process, the upsetting test of cylindrical specimens was carried out and let to determine flow stress–strain relationships [25, 26, 27, 28, 29, 30]. Before upsetting, the specimens were heated in a furnace to established temperature (Figure 1).

Figure 1.

a) Setup of the upsetting/test at high-temperature mounted on 1000 kN hydraulic press, b) flow stress–strain relationships for AZ 31 [28].

On the example of AZ31, AZ61, AZ80, WE43 alloys, and magnesium and lithium alloys, the determined flow stress–strain relationships between flow stress and strain for different values of temperature and strain rate allow for adequate adjustment of plastic deformation parameters based on specific relationships between the structure and deformation under conditions of hot compression test. Documented occurrence of two deformation mechanisms: slip and twinning in the presented relationships between plasticity characteristics such as: maximum yield stress and strain corresponding to the maximum, and the Zener-Hollomon parameter allows for an appropriate interpretation of the effects of microstructure transformation [31]. In order to prepare technological process, it is necessary to define precisely the plastic properties and microstructure changes of those alloys. Comparison of the plasticity and microstructure of magnesium alloys with from 3 to 8% aluminum content from group Mg-Al-Zn-Mn let to choose proper parameters of the process. On the basis of tensile tests, the plasticity changes were determined at temperature from 150 to 450°C. Conducted compression test at temperature from 250 to 450°C and deformation speed from 0.01 to 10 s–1 provided important data concerning the influence of process parameters on flow stress and microstructure changes connected with recrystallization process.

The characteristics of the relationships obtained in the compression test: flow stress σp- strain ε for the tested alloys AZ31, AZ61, AZ80, WE43 (Figure 2), and magnesium alloys with lithium (Figure 3) show the influence of temperature on their course, which allows for an adequate choice of technological parameters for plastic deformation methods with the dominant state of compressive stress (e.g., forging, extrusion).

Figure 2.

Flow stress–strain relationships for magnesium alloys AZ31, AZ61, AZ80, and WE43 obtained in compression test [28].

Figure 3.

Flow stress–strain relationships for magnesium alloy Mg-7,5 Li obtained in compression test [28].

Tests of magnesium and lithium alloys [32] with lithium content of 2.5, 4.5, 7.5, and 15% of the mass showed very different flow stress–strain relationship characteristics plasticizing from deformation, which results from the fact that alloys with 2.5 and 4.5% lithium form a lithium solid solution in magnesium and have a hexagonal structure. The 7.5% lithium alloy has an.

α + two-phase structure β., where the α-phase with the hexagonal structure is a solid solution of lithium in magnesium and the β phase has a wall structure centered is a solution of magnesium in lithium. The 15% lithium alloy is a solution of magnesium in lithium and has a wall-centered structure. An example of the flow stress–strain relationship for Mg-7,5 Li alloy is shown in Figure 3.

Alloys that contain more lithium, which is 7.5%, have good formability at temperature of 150°C. The alloy content of 15% lithium demonstrates very good deformability. The shape of flow curves and microstructure of alloys after deformation at elevated temperatures show significant influence of dynamic recrystallization process.

Determination of the plastic formability can be made on the basis of the results of torsion test too [30].

Flow curves for the magnesium alloy AZ31, most commonly used so far, were determined using torsion test at 300, 400, and 450°C at the speed 1 s−1 (Figure 4), while in the compression test at the temperature of 200, 300, 400, and 450°C at a strain rate of 0.01 and 1 s−1, respectively (Figure 5). AZ31 magnesium alloy exhibits an increase in deformability with an increase in the torsional temperature from 1.2 at 300°C to 5 at 450°C (Figure 4).

Figure 4.

Flow curve of AZ31 alloy determined in torsion test at temperature of 300, 400, and 450°C with a strain rate 1 s−1 [30].

Figure 5.

Flow curve of AZ31 alloy determined in compression test at temperature of 200, 300, 400, and 450°C with a strain rate: a) 0.01 s−1, b) 1 s−1 [30].

Axial-symmetric compression tests carried out on the Gleeble 3800 simulator with simultaneous “freezing” of the microstructure after deformation by rapid cooling with water, in the temperature range from 200 to 450° C with the strain rateέ = 0.1 s−1 and 1,0 s−1, until the deformation ε = 1, 2 (Figure 5) allows the assessment of the influence of these factors on the course of the characteristic and its use in the design of plastic forming processes.

The flow curves obtained in the compression test indicate a similar level of the value of flow stress of the alloy for comparable conditions of its deformation in relation to the torsion curves.

Performing plastometric tests for a magnesium alloy allows the identification of two types of flow curves. Classical curve—where the dominant mechanism in the microstructure is slip (e.g., Figure 6a) and the characteristic curve, where the dominant mechanism in the microstructure is twinning (Figure 6b).

Figure 6.

Microstructure of magnesium alloy AZ31: a) after deformation at temperature of 350°C—Slip domination, b) after deformation at temperature of 250°C—Twinning domination, strain rate 0.1 s−1 [30].

The relationship of the maximum yield stress σpp and strain εp as a function of ln Z, where: Z – Zener-Hollomon parameter, Z=ε̇expQRTis shown in Figures 7 and 8.

Figure 7.

Maximum yield stress σpp as a function lnZ [31].

Figure 8.

Deformation εp corresponding to the maximum yield stress on the flow curve σp as a function lnZ [31].

Currently, plastic forming of magnesium alloys is limited to a few basic grades from the group of Mg Al-Zn (AZ21, AZ31, AZ61) and Mg-Zn-Mn (ZM21) alloys. AZ31 magnesium alloy as the most widely used for rolling metal sheets shows good formability under hot-forming conditions. The obtained flow curves depending on the deformation parameters show two different types of the deformation process. For higher temperatures and lower strain rates, the curve follows the classical course of changes in the yield stress. At lower temperatures and higher strain rates, the course of stress changes is different and characteristic for the process based on the twinning mechanism, which was confirmed in structural studies. It has been shown that there is a relationship between the maximum yield stress σpp and the corresponding strain εp, and the Zener-Hollomon parameter (Figures 7 and 8). A worse fit occurs for curves where twinning dominates, which changes the shape of the curve [30]. Flow stress–strain curves of alloy AZ31 are characteristic for alloy in which during deformation a mechanism of plastic strain called twinning occurs [33].

The microstructure of AZ31 alloy after deformation by hot compression at the temperature of 200, 300, 400, and 450°C with strain rate of 0.01 s−1 and 1 s−1, respectively, was examined, and an example is shown in Figure 9. It was observed after the compression test at 200°C for strain =1.2, for both the strain rates used, the microstructure of the primary elongated grains and the ultrafine grains dynamically recrystallized (Figure 9). Samples deformed at a lower strain rate are characterized by a greater advancement of the recrystallization process. Recrystallized grains are observed both at the boundaries and within the primary grains.

Figure 9.

Microstructure of the AZ31 alloy after compression at temperature 200°C: a) with a strain rate 0.01 s−1, b) with a strain rate 1 s−1 [31].

The microstructure of AZ31 alloy, after deformation at the temperature of 300°C with the speed of 0.01 s−1, consists of fine grains that are dynamically recrystallized. For a higher strain rate, chains of recrystallized grains at the boundaries of the deformed primary grains are observed. Increasing the temperature to 400 and 450°C intensifies the recrystallization processes and grain growth. Few deformation twins are also observed (Figure 10).

Figure 10.

Microstructure of the AZ31 alloy after compression at temperature 450°C: a) with strain rate 0.01 s−1 , b) with strain rate 1 s−1 [25].

The presented results of plasticity tests of AZ31 magnesium alloy indicate its good formability during hot deformation. The fine-grained recrystallized microstructure was obtained at the temperature of 300°C for a low strain rate. Increasing the temperature leads to the growth of recrystallized grains. Consequently, the average grain diameter after deformation at 450°C is much higher than before deformation.

Traditionally, the compression test specimens are circular in cross section. Taking into account the geometrical profiles of plastically formed products, e.g., in the process of forging or extrusion, the cross-sectional geometries are usually more complex. The analysis of the influence of the geometry of the deformed sample in the non-standard compression test when the cross sections of the deformed sample are not circular (Figure 11) shows that the differences are significant in the mechanical behavior of the material (the level and course of the forming force, the change in the geometry of the upset sample).

Figure 11.

Upsetting test specimens.

Taking into account the different geometry of the initial material in the evaluation of the impact of the strain rate and temperature on the forging (upsetting) effect of magnesium alloy specimens (as a material test before designing the forging process) allows for determining the appropriate process parameters.

The results of modeling the upsetting process of magnesium alloys obtained in the form of temperature distributions, stress and strain distribution as well as strain rates provide the basis for determining the conditions of the actual process leading to a product without defects and with high-quality requirements.

The analysis of force courses as a function of displacement during the upsetting process of magnesium alloys showed that the value of the force required for deformation decreases with increasing temperature. The value of the force is strongly influenced by the shape of the upset specimen, including the geometrical parameters (number of corners, the measure of angles, axes of symmetry, and planes of symmetry) (Figure 12).

Figure 12.

The effect of different geometry of initial material (shape of the cross section of the sample) on the force of deformation during upsetting test.

Both in numerical simulation of upsetting and in experimental tests, the values of the force needed to deform individual specimens are convergent. The more complicated the cross-sectional shape, the greater the force needed to deform a given specimen of metallic material.

The results of upsetting test for the forging process demonstrate different mechanical behavior of various Mg alloys: e.g., AZ31 and WE 43, and they are useful to determine plastic formability (Figure 13a and b).

Figure 13.

Influence of temperature on the course of force values during the upsetting of magnesium alloy a) AZ31, b) WE 43.

On the basis of their analysis, it is possible to assess ability to deformation of magnesium alloys on the basis of determining:

3. Processes of metal forming: forging, extrusion, KOBO extrusion, rolling, and joining: friction stir welding. Mechanical properties, microstructure, and quality of the final product. Examples of applications

The analysis of magnesium alloys and their possibilities of deformation by plastic forming shows that they are prospective due to the development of a number of new technologies. The purposefulness of work on the development of the plastic forming technique [34] is primarily determined by the better mechanical properties of plastically processed magnesium alloys compared with the cast ones. Now, there are main groups of magnesium alloys available for plastic deformation:

Designing the processes of metal forming of structural elements made of magnesium alloys requires precise determination of the influence of process parameters on the microstructure and consequently on the mechanical properties of the manufactured elements. This is of particular importance when designing products in aviation [36, 37], automotive, medical, and other applications. Plastic forming tests carried out under laboratory and industrial conditions indicate that selected magnesium alloys can be formed especially in the process of rolling, forging, and extrusion. When forming AZ61, AZ80, and WE43 alloys, the temperature range is significantly limited, both at the beginning and the end of the deformation process. Therefore, to carry out plastic forming, especially forging, it is necessary to have devices that enable the process to be carried out in isothermal conditions. For AZ31 alloy, the range of temperatures of good formability is greater due to the greater tendency of this alloy to the recrystallization process.

The beneficial properties of magnesium alloys are obtained thanks to thermo-plastic treatment. In magnesium alloys, an intensive process of dynamic recrystallization takes place during plastic deformation, which promotes grain refinement and improvement of mechanical properties. Plastic forming of magnesium and its alloys can be carried out, depending on the content of alloying elements, only in a narrow temperature range.

Examples of the use of magnesium alloys in the formation of products/semi-finished products in the processes of plastic forming and joining processes involving plastic deformation (friction stir welding) show the enormous potential of these materials and the clear benefits of using these technologies in the forming of various types of products.

3.1 Particularities of metal forming processes of Mg alloys

3.1.1 Rolling

Rolling of magnesium alloys is currently limited to a few basic grades from the group of Mg Al-Zn and Mg-Zn-Mn alloys. The new alloys Mg-Th- (Mn or Zr) and Mg-Li-Al are also susceptible to rolling [30, 32, 35, 38, 39].

The process of rolling magnesium alloy products is very expensive and time-consuming. This is due to the necessity to carry out annealing between successive operations. As a result of the current growing interest in sheets of magnesium alloys, the so-called “twin rolls casting” technology has been developed, which reduces the number of rolling and heating operations by casting between rolls and subsequent rolling [32].

Rolling AZ31 alloy with heating the billet in a chamber furnace to the temperature of 470°C for 30 minutes and cooling it in the air to the rolling temperature, in the range from 200 to 450°C, allows for obtaining a product with the required mechanical properties at the level of Rm = 220–265 MPa and A50 = 10–12%.

Examples of the microstructure of AZ31 alloy bands after the hot rolling process are shown in Figures 14 and 15. In the microstructure of the specimens rolled with a total draft of 44%, it shows a partially recrystallized structure (Figure 14a). The presence of primary grains and recrystallized grains was found (Figure 14b) fully recrystallized structure with fine grains. The analysis of the microstructure of the AZ31 alloy bands shows that it is precisely the application of large creases (here 82%) that allows obtaining a fine-grained structure without visible areas of primary grains.

Figure 14.

Microstructure of bands from alloy AZ31 after rolling process by total draft: a) 44%, b) 82% [32].

Figure 15.

Microstructure of the AZ31 alloy rolled plate: a) in the surface of the plate, b) in the longitudinal section of the plate, c) in the cross section of the plate [30].

The existing industrial application of magnesium alloys is currently focused on the utilization of semi-finished products such as sheets. The effects of processing parameters and special aspects of the rolling process on the mechanical properties and sheet formability is examined, and recent developments is presented in [37, 40].

3.1.2 Forging

Among the most common forming processes, forging is a promising candidate for the industrial production of magnesium wrought products. The basics of magnesium forging practice are described, and possible problems as well as material properties are presented and discussed in many papers. Several alloy systems containing aluminum, zinc, or rare earth elements as well as biodegradable alloys are evaluated to focus on the process control and processing parameters, from stock material to finished parts including mechanical properties and analysis of microstructure [37, 40, 41].

The final properties of the forgings made of Mg alloys depend on the type of alloy and the string technological process leading to the final product. Most often feet cast magnesium is plastically deformed into semi-finished products, mainly by extrusion or rolling. Usually, forgings are made of semi-finished products in the form of extruded bars or rolled plates, which can be supplied in various conditions depending on the type of heat treatment applied. Forgings after being forged are subjected to precipitation hardening, recrystallization annealing, or stress relief annealing or leaving heat untreated. Each stage of the production line affects the structure and final properties of the product.

Forging as a process of forming the material through multistage deformation for magnesium alloys is a typical process based on hot forming at a narrow temperature range. An example of multistage forging of the airplane wheel hub and the AZ31 magnesium alloy control system lever of the helicopter is shown in Figure 16 [42, 43, 44].

Figure 16.

View of forgings from AZ31 alloy: a) semi-hub of wheel, b) lever after process at beginning temperature of 410°C [28].

Forging should be carried out on hydraulic or low-speed hydraulic presses. In specialist literature, it is not recommended to use die hammers and high-speed presses due to the cracking of the material during forging. When designing the transverse flow tendency of the magnesium alloys, the rod axis as well as difficult flow in the longitudinal direction should be taken into consideration. Die blanks should be polished to facilitate material flow and avoid surface defects. Free removal of the forging from the blank is possible thanks to forging inclinations equal to 3°, and in some cases even smaller [45, 46].

A very important process parameter is the temperature of the charge and tools. Magnesium alloys are good heat conductors and quickly cool down in contact with the tools, the more so that during forging, the material deformed over a relatively long time is in contact with a large surface with the die shape. For this reason, the temperature of the tools should be kept slightly below the load. Too much cooling of the billet leads to the formation of cracks. Conversely, too high a temperature also causes cracking due to the occurrence of hot brittleness. Lubrication is applied during the forging operation. Greases based on graphite or molybdenum disulfide are recommended for the forging temperature range of magnesium alloys.

Magnesium alloys are highly strain rate sensitive and exhibit good workability at a narrow forging temperature range. Consequently, parts made of these materials are usually forged with low-speed hydraulic presses, using specially designed tool heating systems in order to ensure near isothermal conditions. This study investigates whether popular magnesium alloys such as Mg-Al-Zn can be forged in forging machines equipped with high-speed forming tools.

Results presented in work [47] have demonstrated that AZ80A is not suitable for forging with either the screw press or the die forging hammer, that AZ61A can be press- and hammer-forged but to a limited extent, and that AZ31B can be subjected to forging in both forging machines analyzed in the study.

Examples of the application of magnesium alloys in aviation structures obtained by forging indicate the effective use of the possibilities of this technology (Examples shown in Figures 1722).

Figure 17.

Stages of forging of AZ31 semihub of wheel, for aeroplane at temperature of 410°C.

Figure 18.

Stages of forging the helicopter control system lever: a) forging, b) forging AZ31 alloy.

Figure 19.

Drop forgings made in industrial conditions: (a) AZ31B, screw press; (b) AZ31B, forging hammer; (c) AZ61A, screw press; (d) AZ61A, forging hammer [47].

Figure 20.

Microstructure and mechanical feature of magnesium alloys after indirect extrusion [28].

Figure 21.

Complex shape profiles of Mg alloys obtained during indirect extrusion [28].

Figure 22.

Grain size measurements on the cross sections of the extruded profiles: Square, Isosceles triangle, circle, and profiles 1, 2, and 3 of complex shape of cross sections and the billet (Ø100 mm) [28].

The forging process was carried out on a drop forging hammer. The initial material was ingots heated to the initial forging temperature equal to 350°C and 410°C, followed by upsetting, forging, forging in a die blank. The correct forging was obtained for the alloy annealed at 410°C [41, 42, 43, 44].

The results of the research on the forging process in industrial conditions of two selected parts of aircraft structures: i.e., the aircraft wheel hub and the helicopter control system levers showed that the appropriate geometric parameters of these magnesium alloy elements and the determination of the conditions of the hammer forging process allowed for obtaining final products without defects with the required final properties (geometric and mechanical properties).

3.1.3 Extrusion

The conventional process of extrusion of magnesium alloys is carried out at a temperature range from 320 to 450°C, at a speed of 1–25 m/min. The developing method of hydrostatic extrusion allows for plastic deformation at lower temperatures and to obtain greater grain grinding of magnesium alloys [28, 43, 48, 49]. The extrusion process was carried out on a counter-press with a heated container. AZ31, AZ61, AZ80, and WE43 magnesium alloy ingots with a diameter of 100 mm, heated to a temperature of 400°C, were extruded at various speeds from 0.04 to 0.16 m/s and with a different extrusion ratio of 6,25–25. The most favorable effect on the microstructure was observed after billet extrusion with an extrusion ratio of λ = 25 (Figure 20ad). As a result of plastic deformation and recrystallization, fine recrystallized grains were obtained, although in the case of AZ61 and AZ80 alloys, a banded microstructure was observed (Figure 20b and c).

Different shapes of cross section of profiles for aviation application were obtained in the way of backward hot extrusion process. Some results of final products are presented in Figure 21. It is possible to obtain profiles of complex shape with elements of varied wall thickness and with thin walls. Microstructure of tested alloys in initial condition after extrusion is shown in Figure 20. Before deformation the tested alloys AZ31 and AZ61 were characterized by single-phase microstructure of solution α-Mg, whereas in microstructure of alloy AZ80 the presence of intermetallic phase γ-(Mg17Al12) was found and which was confirmed by prior X-ray tests. The extrusion of profiles with a complex cross-sectional shape and large differences in wall thicknesses (Figures 21 and 22) allowed the assessment of high plastic deformation possibilities of these alloys, favorable microstructure, and obtaining very good mechanical properties [28, 49, 50, 51].

The measurements of the grain size (acc. to ASTM E 112) and the microhardness HV0.1 of the magnesium alloy on the cross section of the extruded profile in the characteristic areas A, B, C (Figure 22) show different values of microhardness and grain size (Table 1), which proves the influence of the cross-sectional geometry on the microstructure and properties of the magnesium alloy.

Alloy Cross section zone Grain size—G, Plate I, ASTM E 112 Microhardness HV0.1
AZ31 Billet– Ø 100 mm 7.5 65
Square 7.5 58
Isosceles triangle 8.5 65
7.5 56
Profile 1 A
B
C
10.5
10.5
10
Profile 2 A
B
10
9.5
Profile 3 A
B
C
10
9.5
10
AZ61 Billet– Ø 100 mm 8.5 65
Square 9 56
Isosceles triangle 9.5 62
9.5 63
Profile 1 A
B
C
9
10.5
9,5
Profile 2 A
B
9
10
Profile 3 A
B
C
9
9
9
AZ80 Billet– Ø 100 mm 7.5 60
Square 9.5 58
Isosceles triangle 9.5 60
9.5 59
Profile 1 A
B
C
9.5
9.5
9.5
Profile 2 A
B
9
10
Profile 3 A
B
C
9
9
9

Table 1.

Grain size and hardness HV0.1 of magnesium alloys profiles after extrusion.

Parameters of the direct and hydrostatic extrusions are presented in Table 2. In the field of extrusion of magnesium alloys, the method of hydrostatic extrusion has been developed quite intensively in recent years. Due to favorable thermo-mechanical conditions, the hydrostatic extrusion process can be carried out at lower-temperatures and a greater grain grinding of magnesium alloys [52, 53].

The comparison of microstructures of various magnesium alloys after plastic forming during extrusion with the same extrusion ratio λ = 25 for alloys: AZ31, AZ61, AZ80 WE43 (Figure 23) indicates diametrical differences in the final plastic deformation effect and let to choose adequate alloy for requirements of given possible application.

Mg alloy Direct extrusion Direct extrusion Hydrostatic extrusion Hydrostatic extrusion
temperature [°C] Speed [m/min] temperature [°C] speed [m/min]
AZ31 (Mg-Al-Zn) 320–380 8–15 190 45
AZ61 (Mg-Al-Zn) 320–380 2–4 200 10
ZM21(Mg-Zn-Mn) 320–380 3÷5 200 30

Table 2.

Parameters of the direct and hydrostatic extrusion.

Figure 23.

Microstructures of magnesium alloys after extrusion with the degree of = 25: a – AZ31, b – AZ61, c – AZ80, d – WE43 λ plastic forming.

Research work using magnesium alloys AZ31, AZ61, AZ80, WE 43, and Mg alloy with Li for production of thin-walled profiles showed the potential of the backward extrusion process of magnesium alloys and KOBO extrusion process to apply them for aeronautical applications. It gives the possibility for indicating the best materials and parameters of the process to use, e.g., bridge dies to produce different types of complex shape of cross sections, which are the interest of aviation industry in light extruded products in order to save energy, costs, etc., by reducing aircraft weight.

3.1.4 KOBO extrusion

Processes of severe plastic deformation (SPD) are defined as metal forming processes in which a very large plastic strain is imposed on a bulk process in order to make an ultrafine-grained metal [54]. Possibility to influence on the microstructure and the mechanical properties by heat treatment is also important to plan an SPD process [52, 55]. The KOBO extrusion process as SPD process is an unconventional extrusion method based on the idea of cyclical deformation path change during the process and localized plastic flow [53, 56]. The deformation path change is carried out by setting the die into an oscillating rotary motion around its axis. The method combines the extrusion of the material with an additional plastic deformation caused by reversible torsion of die. Being induced this way super plastic mode of deformation makes possible to deform metals with very high deformation (SPD process) at low temperature (room temperature). Hence, despite very low load capacity of the press, the methods allow for the variety of metallic products to be extruded at room temperature from the billet, with size and dimensions with value of extrusion ratio λ up to several hundreds. The example for KOBO extrusion of MgLi4 is presented in Figure 24.

Figure 24.

a) Scheme of KOBO extrusion process, b) extruded wire of Mg Li4 alloy, extrusion ratio λ = 10,000.

Superplastic behavior of a metals under such deformation conditions is proven also in exact filling of a die opening, regardless how complicated it is and mode of extrusion forward or sideway. The most important advantage of the KOBO method is the ability to deform metals with a very high λ coefficient (extrusion ratio) [53, 57, 58, 59] in the “cold” process (without preheating the billet or tooling), regardless of the hardening state of the initial material. The use of the KOBO method allows for reducing the work of deformation, so the extrusion forces are incomparably lower than in conventional extrusion processes. The examples of measured parameters of KOBO process for magnesium alloys AZ31 and WE43 are shown in Figure 25.

Figure 25.

a) Extrusion of magnesium alloy AZ31 round bar with stable extrusion speed. b) Extrusion of magnesium alloy WE43 round bar with stable extrusion speed. c) Extruded round bar ϕ3 mm.

KOBO extrusion is a process carried out in a system of concurrent extrusion with an oscillating matrix. In turn, the possibility of forming the products of a specific cross-sectional shape, as in conventional extrusion processes, makes it possible to obtain products, not only specimens, with very fine grains and favorable mechanical properties, which qualify the KOBO method for potential industrial implementations. The significant reduction of the extrusion load and the lack of the need for preheating make the method very economically attractive. Another, extremely attractive feature of the KOBO method is the possibility of low-temperature consolidation of postprocessing chips [28, 53, 57, 58, 59, 60, 61, 62, 63, 64] and obtaining a solid product as a result of plastic deformation in the process. The deformation effects of magnesium alloys, both in the form of a solid billet and in the form of consolidated postprocessing chips, are shown in Figure 26.

Figure 26.

Extrusion of metal chips in the KOBO process: a) a chip before and after compaction of chips into billet, b) an extruded monolithic profile, c) extrusion of solid profile of complex shape of cross section.

Low temperature—above 200°C in KOBO extrusion technology of magnesium alloys, possibility to control the final properties of the extruded profiles let to maintain a fine grain structure of the alloys [65]. It comes from the number of KOBO process parameters, such as amplitude and frequency of die oscillations. It is possible to use the backward extrusion and KOBO processes for bulk metals and chips. To determine proper parameters of extrusion process, it is necessary to know exact information on initial features of given magnesium alloy—its macro and microstructure, mechanical properties, and final results of transformation of the internal structure under conditions of plastic deformation.

3.1.5 Joining. Friction Stir Welding

Joining. Friction Stir Welding FSW is solid-state joining process under the influence of frictional heat. There is no melting involved in the process unlike conventional fusion welding process. The FSW process was originally invented in institute TWI in the United Kingdom in 1991 [65, 66, 67]. The principle of utilizing the frictional heat between a rotating tool and the two joining metal interfaces is shown in Figure 27.

Figure 27.

Scheme of linear Friction stir welding process.

The rotating tool serves two basic purposes: heating of the workpiece materials due to friction and plastic deformation and stir movement and containment of materials to produce joint. Rotating tool with a specially designed pin and shoulder is inserted into the abutting edges of sheets or plates to be joined and subsequently traversed along the joint line. Advancing and retreating side orientations require knowledge of the tool rotation and travel directions. It is especially important when FSW process is designed for given metallic material. Magnesium alloys require special attention from the point of view of adequate parameters choice, especially for joining very thin sheets, because FSW process is very sensitive to the technological parameters of welding. From the point of view of plasticization of metals, the FSW process is very complex. The rotating tool in the first phase of the process supplies more and more heat, then the welded material is strongly deformed plastically. The material, in contact with the pin of the moving tool, experiences a state of stress and deformation comparable to that in extrusion and forging. The last stage is cooling of the weld [67]. It is important to know the influence of the selected technological and geometrical parameters of the process on the plasticization of the materials to be joined. Assessment of joint quality on the basis of tests of the mechanical properties of the obtained joints (static strength, fatigue strength, microhardness), microstructure tests in the area of weld, and parent material as well as the measurement of forces acting on the tool as a material response to the load resulting from the adopted process conditions. As a result of the conducted research on linear, FSW stir-mixed butt welding of thin sheets with a thickness of 0.5 mm made of AZ31B magnesium alloy, the basic goal was achieved, which was to obtain a solid, durable, free from defects connection of elements. When welding 0.5 mm thick sheets, the variable parameters were the rotational speed and the tool feed. The friction stir welding process was carried out with the use of magnesium alloy sheets, including AZ31B, 0.5 mm thick. The FSW joining process was carried out as a butt joint. An example of a connection is shown in Figure 28.

Figure 28.

FSW joints: a) view of joint with advancing and retreating sides, b) FSW joint of the AZ31B magnesium alloys, a) face and ridge of joint FSW joint of AZ31 B sheets of 0.5 mm of thickness, l = 180 mm.

Due to the difficult conditions for the implementation of the process, an important issue is the selection of an appropriate tool with the appropriate geometry and kind of material of the tool. During FSW welding of magnesium sheets a cemented carbide tool was used. Taking into account the interdependence of mechanical and structural effects in the FSW process, special attention should also be paid to the analysis of the microstructure in the joint area, identification of characteristic zones as a result of the transformation of the microstructure resulting from the plasticization of the joined materials and the generated heat due to friction and plastic deformation, heat dissipation, among others in contact with the tool and tooling and the overall heat balance resulting in the final state of the joint. These are issues for thin sheets, especially for light metals (aluminum alloys, magnesium alloys) [68, 69]. Figure 29 shows the FSW weld microstructure of a sheet with a thickness of 0.5 mm of AZ31B alloy. The presented sample was made with the welding speed of 80 mm/min and the tool rotation speed of 2000 rpm. It is difficult to identify the zones characteristic for the FSW joint in the case of welding very thin sheets. In this case, the locations of areas such as the heat affected zone, the thermomechanical interaction zone, and the weld core were estimated based on the dimensions of the tool. The area of direct contact of the rim of the tool resistance is characterized by fragmented grain due to high plastic deformation. Equal-axis grain was also observed in the HAZ (heat-affected zone) and TMAZ (thermomechanical-affected zone) as shown in Figure 28.

Figure 29.

Typical scheme of zones of butt FSW joint (SZ – Stir zone/nugget zone, TMAZ – Thermomechanically affected zone/HAZ – Heat-affected zone/BM – Base material/parent material, RS – Retreating side, AS – Advancing side).

The presence of equiaxed grains in the HAZ and TMAZ zone indicates that the material has fully recrystallized during the FSW process. The dynamics of recrystallization affects the grain size. Magnesium alloys are more prone to dynamic recrystallization than aluminum alloys because the Mg recrystallization temperature is approximately 523 K—lower than that for aluminum alloys. The factor that inhibits grain growth as a result of high temperature is also the cooling rate. In ultrathin materials (sheet thickness equal to or less than 0.5 mm), it is relatively high—the material cools down quickly, which is noticeable already during the process. The joint shown in Figure 30 does not contain any crater defects or discontinuities.

Figure 30.

Typical microstructures of an FSW joint made at different rotational speed and welding speed. a) Microscopic structure of FSW welded AZ31B of 0.5 mm in thickness. View of base material BM. b) Microscopic structure of FSW welded AZ31B of 0.5 mm in thickness. View of HAZ and TMAZ zone from the retreating side. c) Microscopic structure of FSW welded AZ31B of 0.5 mm in thickness. View of stir zone SZ and TMAZ of advancing side.

The obtained results of the FSW joining process of magnesium alloys showed that the process of linear friction stir welding (FSW) is a favorable method of joining difficult-to-weld magnesium alloys [70, 71, 72, 73]. Appropriate selection of parameters allows for obtaining joints free from defects. The assessment of the quality of the joints made on the basis of: the results of the joint microstructure analysis, measurements of the microhardness of the joint and the base material as well as the static tensile test of the weld material allowed for an unambiguous determination of the joint effectiveness. Proper selection of technological and geometric parameters allows for obtaining a connection with approximately 90% efficiency in relation to the parent material, determined on the basis of a static tensile test. During the tensile test, all joints broke in the thermomechanical impact zone on the retreating side. This is due to the resulting structural notch at the boundary of the weld nucleus and the thermomechanical influence zone. When welding 0.5 mm thick sheets of Mg AZ31B alloy, the maximum force acting on the tool in the Z axis was 4.5 kN. The values of the forces acting on the tool in the radial direction range from 40 to 100 N. After making a total of approximately 20 m of linear FSW weld, the tungsten carbide tool was not worn according to visual assessment. The FSW process is an excellent alternative to riveting or conventional welding. It does not require the use of an additional connector, which contributes to reduce the weight of the structure. Friction stir welding of the FSW joint allows for the creation of a high-quality, durable, defect-free joint with high mechanical properties (static and dynamic tests) and favorable internal structure of the AZ31B alloy sheet material.

The average obtained connection efficiency with appropriately selected input parameters of the process ranges from 85 to 95% compared with the parent material. These values are fully acceptable to the aviation (min. 80%) and automotive (min. 70%) industries. The analysis of the variability of forces generated during the FSW process requires knowledge of material properties and process conditions. It is necessary to adequately select the process parameters to the type of alloy and thickness of the joined elements (Figure 31).

Figure 31.

Matrix of technological parameters for joining AZ31B alloy sheets of 0.5 mm thickness [68].

The estimated value of the FSW process temperature should be approximately 0.8 solidus temperature. In this case, for alloy AZ31B, solidus temperature is 605°C, so temperature for FSW process is 430°C. AZ31 alloy with aluminum as the main alloy additive is very brittle at room temperature (only one slip plane (0001)). Only when the temperature of 200°C is exceeded, other slip planes are activated, which facilitates further plastic deformation. Reaching the temperature of 200°C is associated with the phenomenon of recrystallization. Achieving these conditions during welding is possible while providing the rotating and plunging tool with a sufficiently long time stoppage. This treatment is necessary to heat the material due to the pressure and friction of the rotating tool (dwell time). The recorded force courses may indicate the most favorable time to achieve the plasticizing effect and achieve the appropriate plasticization conditions of the material over 450 MPa, which exceeds the value of the yield stress for AZ31B alloy. A sudden increase in radial forces acting on the tool was noticed. Then the welding stage begins, where the stabilization of both axial and radial forces was observed. Very good results of joining thin sheets of the AZ31 B alloy [64, 65, 66, 67, 68, 69, 74, 75] prove the purposeful use of friction stir welding to join sheets of various thicknesses. Butt joints with smooth surface, without voids and flash, can be obtained by cylindrical flat shoulder and pin tool made from tungsten carbide. Tensile tests revealed a durability increase up to 90% compared with BM, which is thought to be mainly attributed to the preferred basal orientation and the activation of the extension twins. The SZ and TMAZ experienced full dynamic recrystallization and thus consisted predominantly of equiaxed grains. The grain size in SZ increased with increasing heat input.

During the FSW, the process must be carried out at the temperature preferably higher than the recrystallization temperature of the base material BM to be joined for the dynamic recrystallization to take place in the SZ. With increasing tool rotational speed or decreasing welding speed supplied more heat energy and generated a higher temperature in stir zone SZ. This led to a weaker or more random texture stemming from the occurrence of more complete dynamic recrystallization. After the FSW of AZ31B alloy of 0.5 mm in thickness, the lowest hardness occurred at the center of SZ through the HAZ and TMAZ of the welded joints; however, the differences are minor.

The welding speed and rotational speed had a strong effect on the UTS (ultimate tensile strength). When choosing the technological parameters for the process, tool feed rate played an important role compared with a tool rotation speed. The plastic flow in the welded regions is also observed with uniform grain orientation.

4. Summary

The development of plastic forming processes as well as joining processes, such as FSW, is primarily determined by better mechanical properties of plastically processed magnesium alloys compared with castings. Designing the technology of plastic forming of structural elements made of magnesium alloys requires precise determination of the influence of the process parameters on the microstructure and consequently on the mechanical properties of the manufactured elements. This is of particular importance when designing products made of magnesium alloys for structural elements for the aviation industry. The selected results of plastic forming research carried out in material tests and technological processes, under laboratory or industrial conditions presented in this chapter, indicate that selected magnesium alloys can be formed by plastic forming methods, especially by rolling, extrusion, and KOBO extrusion and forging. When forming AZ61, AZ80, and WE43 alloys, the temperature range is significantly limited, both at the beginning and the end of the deformation process. Therefore, to carry out plastic forming, especially forging, it is necessary to have devices that enable the process to be carried out in isothermal conditions. For AZ31 alloy, the range of temperatures of good formability is greater due to the greater tendency of this alloy to the recrystallization process. Thus, it is possible to manufacture AZ31 alloy products on conventional devices, but the obtained mechanical properties are less favorable than other magnesium alloys.

Magnesium-lithium alloys deserve attention due to their plastic formability, mechanical properties, and low specific weight, which makes them very attractive wherever lightweight and durable structures are desired. Elements manufactured by plastic processing of magnesium alloys and new technologies involving plastic deformation, including joint friction welding (FSW) technologies, are currently successfully implemented in various sectors of the economy.

Magnesium and its alloys are mainly used as a construction material (most often in the form of castings from magnesium alloys, but also plastically formed products), as an alloy additive to aluminum alloys, and for desulfurization of iron and steel. Due to the low specific mass and high relative strength, magnesium alloys in the form of castings or plastically formed products are used in such industries such as: aviation and aerospace, for the production of aircraft and rocket parts, including engine parts, gearbox components, hinges, fuel tanks, wing elements; automotive, for the production of, among others car rims, various types of housings, engine blocks, steering wheels, seat frames, windows and doors, body parts; sports and recreational, for bicycle parts and elements of various sports equipment articles; electronic, mainly for the production of various types of electronic equipment housings; medical, for strengthening elements in bone fractures. Examples of applications of magnesium alloys in the aviation industry include: Rolls Royce gear housing made of ZRE1 alloy Pratt & Whitney Canada PW535 engine housing made of ZE41 alloy, helicopter parts. In the automotive sector, the examples are steering wheel, boot lid; manufacturer GM, BMW engine block; cross section of the outer layer made of Mg alloy revealing the inner layer of Al alloy.

Now it is time for the successful application of magnesium-based materials. It is particularly important to promote exchange of information and discussion in which development trends and application potential in different fields such as the automotive industry and communication technology in an interdisciplinary framework [37, 72, 73].

Acknowledgments

The author gratefully acknowledges the collaboration and discussions with.

Prof. Eugeniusz. Hadasik and Prof. Andrzej Gontarz, who provided support and information on magnesium research and application.

Financial support of Structural Funds in the Operational Program–Innovative Economy (IE OP) financed from the European Regional Development Fund–Project “Modern material technologies in aerospace industry,” Nr POIG.01.01.02-00-015/08-00 is gratefully acknowledged.

\n',keywords:"magnesium alloys, plastic formability, forging, extrusion, KOBO extrusion, rolling, joining, friction stir welding",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79745.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79745.xml",downloadPdfUrl:"/chapter/pdf-download/79745",previewPdfUrl:"/chapter/pdf-preview/79745",totalDownloads:53,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 27th 2021",dateReviewed:"October 1st 2021",datePrePublished:"February 18th 2022",datePublished:"March 23rd 2022",dateFinished:"December 20th 2021",readingETA:"0",abstract:"The chapter presents an analysis of selected magnesium alloys as structural materials to be used in production of parts as well as their technological parameters in some manufacturing processes: metal forming and joining. Taking into account the analysis of microstructure and mechanical properties of conventional and new magnesium alloys and requirements of their possible applications (aviation, automotive, sport, etc.), the study of forming parts/products based on description of plastic formability of magnesium alloys in the processes of bulk metal forming (forging, extrusion, KOBO extrusion, rolling) and joining (friction stir welding) has been presented. Upsetting test, backward extrusion, and KOBO extrusion of complex cross-sectional profiles and forging process were conducted using magnesium alloys such as AZ31, AZ61, AZ80, WE 43, and Mg alloy with Li for the production of thin-walled profiles and forged parts. The range of temperatures and extrusion rate for manufacturing of these profiles were determined. Tests also covered the analysis of microstructure of Mg alloys in the initial state as well as after the extrusion process. The recommendations for realization of metal forming and joining processes of selected magnesium alloys have been presented.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79745",risUrl:"/chapter/ris/79745",signatures:"Romana Ewa Śliwa",book:{id:"9926",type:"book",title:"Magnesium Alloys Structure and Properties",subtitle:null,fullTitle:"Magnesium Alloys Structure and Properties",slug:"magnesium-alloys-structure-and-properties",publishedDate:"March 23rd 2022",bookSignature:"Tomasz Tański and Paweł Jarka",coverURL:"https://cdn.intechopen.com/books/images_new/9926.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-467-4",printIsbn:"978-1-83962-458-2",pdfIsbn:"978-1-83962-468-1",isAvailableForWebshopOrdering:!0,editors:[{id:"15700",title:"Prof.",name:"Tomasz Arkadiusz",middleName:null,surname:"Tański",slug:"tomasz-arkadiusz-tanski",fullName:"Tomasz Arkadiusz Tański"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"328793",title:"Prof.",name:"Romana",middleName:"Ewa",surname:"Ewa Śliwa",fullName:"Romana Ewa Śliwa",slug:"romana-ewa-sliwa",email:"rsliwa@prz.edu.pl",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Rzeszów University of Technology",institutionURL:null,country:{name:"Poland"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Evaluation of plastic formability of Mg alloys",level:"1"},{id:"sec_3",title:"3. Processes of metal forming: forging, extrusion, KOBO extrusion, rolling, and joining: friction stir welding. Mechanical properties, microstructure, and quality of the final product. Examples of applications",level:"1"},{id:"sec_3_2",title:"3.1 Particularities of metal forming processes of Mg alloys",level:"2"},{id:"sec_3_3",title:"3.1.1 Rolling",level:"3"},{id:"sec_4_3",title:"3.1.2 Forging",level:"3"},{id:"sec_5_3",title:"Table 1.",level:"3"},{id:"sec_6_3",title:"3.1.4 KOBO extrusion",level:"3"},{id:"sec_7_3",title:"3.1.5 Joining. Friction Stir Welding",level:"3"},{id:"sec_10",title:"4. Summary",level:"1"},{id:"sec_11",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'www.simflight.com [Accessed: March 31, 2010]'},{id:"B2",body:'www.fas.org [Accessed: March 31, 2010]'},{id:"B3",body:'Kawalla R. Magnez i stopy magnezu. 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Obróbka Plastyczna Metali. 2016;XXVII(2):133-152'},{id:"B62",body:'Zwolak M, Śliwa RE, An effect geometry, parameters of surface structure and material properties of KOBO extrusion dies on plastic flow of metals to produce lightweight profiles for aviation. 11th Aluminium Two Thousand World Congress 9–13 APRIL 2019 TREVISO'},{id:"B63",body:'Zwolak M, Śliwa RE, Pawłowska B. Analysis of plastic flow of metallic materials with different billet structure under the conditions of the KOBO extrusion process. In: Conference Proceedings FORMING, Ladek Zdrój. 2018'},{id:"B64",body:'Zwolak M, Sliwa RE, Pawłowska B. Kształtowanie mikrostruktury wyciskanego metalu w różnych warunkach procesu KoBo. In: Materiały XIII Konferencji Naukowej nt.: Odkształcalność Metali i Stopów. Omis, Łańcut: Oficyna Wydawnicza PRz; 2019'},{id:"B65",body:'Thomas WM, Dolby RE. Friction Stir welding developments. In: David SA, Deb Roy T, Lippold JC, Smartt HB, Vitek JM, editors. 6th Int. Trends in Welding Research. Materials Park, Ohio, USA: ASM International; 2003. pp. 203-211'},{id:"B66",body:'Thomas WM, Nicholas ED, Needham JC, Murch MG, Temple-Smith P, Dawes CJ. Friction stir butt welding. International Patent Application no. PCT/GB92/02203. 1991'},{id:"B67",body:'Seidel T, Reynolds AP. Visualization of the material flow in AA2195 friction-stir welds using a marker insert technique. Metallurgical and Materials Transactions A. 2001;32(11):2879-2884. DOI: 10.1007/s11661-001-1038'},{id:"B68",body:'Mysliwiec P. Analiza efektu uplastycznienia cienkich blach ze stopów aluminium i magnezu w procesie zgrzewania tarciowego z przemieszaniem do zastosowania w konstrukcjach lotniczych i samochodowych. PhD Thesis, Rzeszów 2020'},{id:"B69",body:'Śliwa RE, Myśliwiec P, Ostrowski R, Bujny M. Possibilities of joining different metallic parts of structure using friction stir welding methods. Procedia Manufacturing. 2019;27:158-165'},{id:"B70",body:'Balawender T, Śliwa RE, Gałaczyński T. Friction stir welding of light alloys. 9th Int. Conf. AIRTEC “Supply on the wings”. Frankfurt/Main; 2014'},{id:"B71",body:'Powell BR, Luo AA, Krajewski PE. Magnesium alloys for lightweight powertrains and automotive bodies. Chapter in book: Advanced Materials in Automotive Engineering. 2012. pp. 150-209'},{id:"B72",body:'Mordike BL, Kainer KU. Magnesium Alloys and their Applications. Wolfsburg: Werkstoff- Informationsgesellschaft; 1998'},{id:"B73",body:'Dobrzański LA, Bamberger M, George ET. Magnesium and Its Alloys: Technology and Applications. Teylor Francis Group; 2021'},{id:"B74",body:'Dorbane, Ayoub G, Mansoor B, Hamade RF, Kridli G, Shabadi R, et al. microstructural observations and tensile fracture behavior of FSW twin roll cast AZ31 Mg sheets. Materials Science & Engineering A. 2016;649:190-200 FSW'},{id:"B75",body:'Lacki P, Kucharczyk Z, Śliwa RE, Gałaczyński T. Effect of tool shape on temperature field in friction stir spot welding. 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Aesthetics",isOpenForSubmission:!1,hash:"938b8668018c9338fbc8992e8e03f971",slug:"mind-and-matter-challenges-and-opportunities-in-cognitive-semiotics-and-aesthetics",bookSignature:"Asun López-Varela Azcárate",coverURL:"https://cdn.intechopen.com/books/images_new/10978.jpg",publishedDate:"April 6th 2022",numberOfDownloads:701,editors:[{id:"302731",title:null,name:"Asun",middleName:null,surname:"López-Varela Azcárate",slug:"asun-lopez-varela-azcarate",fullName:"Asun López-Varela Azcárate"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10633",title:"Biotechnology to Combat COVID-19",subtitle:null,isOpenForSubmission:!1,hash:"d834c746c5b159a201a9cdadfc473486",slug:"biotechnology-to-combat-covid-19",bookSignature:"Megha Agrawal and Shyamasri Biswas",coverURL:"https://cdn.intechopen.com/books/images_new/10633.jpg",publishedDate:"February 23rd 2022",numberOfDownloads:7493,editors:[{id:"193723",title:"Dr.",name:"Megha",middleName:null,surname:"Agrawal",slug:"megha-agrawal",fullName:"Megha Agrawal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"10843",title:"Persistent Organic Pollutants (POPs)",subtitle:"Monitoring, Impact and Treatment",isOpenForSubmission:!1,hash:"f5b1589f0a990b6114fef2dadc735dd9",slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",bookSignature:"Mohamed Nageeb Rashed",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",editedByType:"Edited by",publishedDate:"April 13th 2022",editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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Alimi, Oluyomi Aboderin, Nelson J. Muga and António L. Teixeira",coverURL:"https://cdn.intechopen.com/books/images_new/10269.jpg",editedByType:"Edited by",publishedDate:"April 6th 2022",editors:[{id:"208236",title:"Dr.",name:"Isiaka",middleName:"Ajewale",surname:"Alimi",slug:"isiaka-alimi",fullName:"Isiaka Alimi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11038",title:"Vaccine Development",subtitle:null,isOpenForSubmission:!1,hash:"2604d260662a3a3cc91971ea07beca61",slug:"vaccine-development",bookSignature:"Yulia Desheva",coverURL:"https://cdn.intechopen.com/books/images_new/11038.jpg",editedByType:"Edited by",publishedDate:"April 6th 2022",editors:[{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11039",title:"Diabetic Eye Disease",subtitle:"From Therapeutic Pipeline to the Real World",isOpenForSubmission:!1,hash:"22986eb45c0b2692661bc8f8804045d0",slug:"diabetic-eye-disease-from-therapeutic-pipeline-to-the-real-world",bookSignature:"Giuseppe Lo Giudice",coverURL:"https://cdn.intechopen.com/books/images_new/11039.jpg",editedByType:"Edited by",publishedDate:"April 6th 2022",editors:[{id:"87607",title:"M.D.",name:"Giuseppe",middleName:null,surname:"Lo Giudice",slug:"giuseppe-lo-giudice",fullName:"Giuseppe Lo Giudice"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10541",title:"Regulation and Dysfunction of Apoptosis",subtitle:null,isOpenForSubmission:!1,hash:"1d45e84353c25037adb996a7a46c1af1",slug:"regulation-and-dysfunction-of-apoptosis",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/10541.jpg",editedByType:"Edited by",publishedDate:"April 6th 2022",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"880",title:"Ecosystem",slug:"environmental-sciences-soil-science-ecosystem",parent:{id:"142",title:"Soil Science",slug:"environmental-sciences-soil-science"},numberOfBooks:2,numberOfSeries:0,numberOfAuthorsAndEditors:72,numberOfWosCitations:68,numberOfCrossrefCitations:55,numberOfDimensionsCitations:109,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"880",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"6316",title:"Peat",subtitle:null,isOpenForSubmission:!1,hash:"6f47ea9e0e0a431c0bd28420154a4727",slug:"peat",bookSignature:"Bülent Topcuoğlu and Metin Turan",coverURL:"https://cdn.intechopen.com/books/images_new/6316.jpg",editedByType:"Edited by",editors:[{id:"194133",title:"Prof.",name:"Bülent",middleName:null,surname:"Topcuoğlu",slug:"bulent-topcuoglu",fullName:"Bülent Topcuoğlu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5358",title:"Soil Contamination",subtitle:"Current Consequences and Further Solutions",isOpenForSubmission:!1,hash:"e4d136df9f1658ae17f3ba7b3c992460",slug:"soil-contamination-current-consequences-and-further-solutions",bookSignature:"Marcelo L. Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/5358.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"52211",doi:"10.5772/64940",title:"Cyanobacterial Toxins Emerging Contaminants in Soils: A Review of Sources, Fate and Impacts on Ecosystems, Plants and Animal and Human Health",slug:"cyanobacterial-toxins-emerging-contaminants-in-soils-a-review-of-sources-fate-and-impacts-on-ecosyst",totalDownloads:4257,totalCrossrefCites:5,totalDimensionsCites:21,abstract:"In the last few decades, there has been a growing interest in the occurrence of cyanotoxins and their potential toxicity in the aquatic environment. However, the used of dried toxic cyanobacteria cells as fertilizer or the used of surface water contaminated with cyanotoxins for agricultural crops irrigation can be source of soil contamination. In addition, surface waters presenting dense toxic blooms of cyanobacteria and used for agricultural practices are not controlled and are often used without prior treatment. Once in soil, cyanotoxins may be transported again to water bodies by leaching, runoff and drainage processes or can be accumulated in soils and, therefore, may cause contamination of vegetation by absorption from soils or by surface pollution of plants. In addition to possible effects on human health, elevated levels of cyanotoxins in soils can negatively affect plant vigour, animal health, microbial processes and overall soil health. Consequently, the focus of this chapter of soil contamination is cyanotoxins as contaminants of emerging concern in the soil, identifying sources of contamination, determining their fate and effects in the soil, and understanding their bioaccumulation in agricultural plants used for feed and food and consequences on animal and human health.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"Noureddine Bouaïcha and Sylvain Corbel",authors:[{id:"186021",title:"Dr.",name:"Noureddine",middleName:null,surname:"Bouaïcha",slug:"noureddine-bouaicha",fullName:"Noureddine Bouaïcha"},{id:"186034",title:"Dr.",name:"Sylvain",middleName:null,surname:"Corbel",slug:"sylvain-corbel",fullName:"Sylvain Corbel"}]},{id:"52054",doi:"10.5772/64735",title:"Radioactive Contamination of the Soil: Assessments of Pollutants Mobility with Implication to Remediation Strategies",slug:"radioactive-contamination-of-the-soil-assessments-of-pollutants-mobility-with-implication-to-remedia",totalDownloads:8531,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"Accidental releases, nuclear weapons testing, and inadequate practices of radioactive waste disposal are the principal human activities responsible for radioactive contamination as a new and global form of soil degradation. Understanding the radionuclide distribution, mobility and bioavailability, as well as the changes caused by the variation of environmental conditions, is essential for soil rehabilitation. This chapter aims to highlight the importance of evaluating radionuclide distribution, for the selection of proper in situ or ex situ remediation strategy. Attention was focused onto remediation methods based on radioactive pollutants redistribution, for enhanced separation (chemical extraction) or containment (in situ immobilization). When the excavation and off-site leaching treatments are uneconomic, impractical, or unnecessary, in situ stabilization by the addition of appropriate reactive materials is an alternative approach. The optimization of factors in control of chemical leaching methods, selection of cost-effective immobilization agents, especially among suitable wastes and by-products, and verification of long-term effects of remediating actions are the major challenges for future investigation in this field. Furthermore, the improvement and standardization of the methods for radionuclide speciation are necessary to enable comparison between studies and monitoring of the effects achieved by the soil treatments.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"Ivana Smičiklas and Marija Šljivić-Ivanović",authors:[{id:"186699",title:"Ph.D.",name:"Marija",middleName:null,surname:"Sljivic-Ivanovic",slug:"marija-sljivic-ivanovic",fullName:"Marija Sljivic-Ivanovic"},{id:"186801",title:"Dr.",name:"Ivana",middleName:null,surname:"Smičiklas",slug:"ivana-smiciklas",fullName:"Ivana Smičiklas"}]},{id:"51942",doi:"10.5772/64682",title:"Approaches for Removal of PAHs in Soils: Bioaugmentation, Biostimulation and Bioattenuation",slug:"approaches-for-removal-of-pahs-in-soils-bioaugmentation-biostimulation-and-bioattenuation",totalDownloads:2039,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"Polycyclic aromatic hydrocarbons (PAHs)‐contaminated soils have been a concern during last decades; consequently, physicochemical and biological technologies have emerged and evolved with the aim of remediating them. Particularly, biological technologies are considered promising since they are low cost, safe and environmentally friendly. However, their results so far have been diverse and scattered. This chapter includes a review of the current status on bioaugmentation, biostimulation and bioattenuation techniques, which have been applied in PAHs‐contaminated agricultural soils during the last decades. Successes and failures in PAHs remediation applied at microcosm and field levels are exhibited. Furthermore, the effects of microbial inoculum, the soil organic matter and the particle size of the aggregates on the PAHs’ availability and on the subsequent microbial biodegradation are reviewed. Finally, agricultural management systems are considered in the prediction of the behaviour and the end‐point of some contaminants, as well as in the success of applying a biological technique.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"María S. Vásquez‐Murrieta, Oscar J. Hernández‐Hernández, Juan A.\nCruz‐Maya, Juan C. Cancino‐Díaz and Janet Jan‐Roblero",authors:[{id:"181148",title:"Dr.",name:"Juan C.",middleName:null,surname:"Cancino-Diaz",slug:"juan-c.-cancino-diaz",fullName:"Juan C. Cancino-Diaz"},{id:"184949",title:"Dr.",name:"Janet",middleName:null,surname:"Jan-Roblero",slug:"janet-jan-roblero",fullName:"Janet Jan-Roblero"},{id:"186305",title:"MSc.",name:"Oscar",middleName:null,surname:"Hernández-Hernández",slug:"oscar-hernandez-hernandez",fullName:"Oscar Hernández-Hernández"},{id:"186307",title:"Dr.",name:"María",middleName:null,surname:"Vásquez-Murrieta",slug:"maria-vasquez-murrieta",fullName:"María Vásquez-Murrieta"},{id:"186308",title:"Dr.",name:"Juan",middleName:null,surname:"Cruz-Maya",slug:"juan-cruz-maya",fullName:"Juan Cruz-Maya"}]},{id:"62735",doi:"10.5772/intechopen.79171",title:"Peat Use in Horticulture",slug:"peat-use-in-horticulture",totalDownloads:1521,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Peat is a spongy substance which is an effect of incomplete decomposition of plant residues in different stages of decomposition. Between the several organic matters which are used as substrate for horticultural plants cultivation in soilless conditions, peat is the unabandonable ingredient for mixtures for commercial production of plants. Peat is used in horticulture as a component of garden plant substrates, in agriculture for the production of garden soil and as an organic fertilizer, and in balneology as a material for baths and wraps. The use of peat for agriculture and horticulture is determined by the following quality parameters: the degree of decomposition, ash content, pH, the presence of carbonates, the density of the solid phase, bulk density, and porosity. As an organic material, the peat forms in the acidic, waterlogged, and sterile conditions of fens and bogs. The conditions seem like the development of mosses. The plants do not compose as they die. Instead of this, the organic matter is laid down and accumulates in a slow time as peat due to the oxygen deficiency in the bog. This makes peat a highly productive growing medium. In the present novel review, we discuss the peat use in horticulture.",book:{id:"6316",slug:"peat",title:"Peat",fullTitle:"Peat"},signatures:"Nurgul Kitir, Ertan Yildirim, Üstün Şahin, Metin Turan, Melek Ekinci,\nSelda Ors, Raziye Kul, Hüsnü Ünlü and Halime Ünlü",authors:[{id:"140612",title:"Prof.",name:"Metin",middleName:null,surname:"Turan",slug:"metin-turan",fullName:"Metin Turan"},{id:"186637",title:"Dr.",name:"Nurgül",middleName:null,surname:"Kıtır",slug:"nurgul-kitir",fullName:"Nurgül Kıtır"},{id:"186639",title:"Prof.",name:"Ertan",middleName:null,surname:"Yildirim",slug:"ertan-yildirim",fullName:"Ertan Yildirim"},{id:"247120",title:"Prof.",name:"Melek",middleName:null,surname:"Ekinci",slug:"melek-ekinci",fullName:"Melek Ekinci"},{id:"247121",title:"Prof.",name:"Selda",middleName:null,surname:"Örs",slug:"selda-ors",fullName:"Selda Örs"},{id:"247122",title:"MSc.",name:"Raziye",middleName:null,surname:"Kul",slug:"raziye-kul",fullName:"Raziye Kul"},{id:"247123",title:"Prof.",name:"Üstün",middleName:null,surname:"Şahin",slug:"ustun-sahin",fullName:"Üstün Şahin"},{id:"260571",title:"Prof.",name:"Hüsnü",middleName:null,surname:"Ünlü",slug:"husnu-unlu",fullName:"Hüsnü Ünlü"},{id:"260572",title:"Dr.",name:"Halime",middleName:null,surname:"Ünlü",slug:"halime-unlu",fullName:"Halime Ünlü"}]},{id:"51941",doi:"10.5772/64771",title:"Copper Contamination in Mediterranean Agricultural Soils: Soil Quality Standards and Adequate Soil Management Practices for Horticultural Crops",slug:"copper-contamination-in-mediterranean-agricultural-soils-soil-quality-standards-and-adequate-soil-ma",totalDownloads:1772,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"This chapter increases the knowledge on the management of Cu-contaminated Mediterranean agricultural soils, by analysing the current soil quality standards for different Mediterranean regions and proposing new criteria for their establishment based on the influence of soil properties and type of crop. We evaluate the effect of Cu and its interaction with soil properties on biomass production of lettuce (Lactuca sativa L.) and tomato (Solanum lycopersicum L.), by establishing the effective concentrations EC50 and EC10 (effective concentrations of Cu in soil that reduces biomass production by 50 and 10%, respectively), and its absorption, translocation and accumulation in the different parts of the plant. Two different biomass assays were carried out in seven types of Mediterranean agricultural soils (four from Europe and three from Australia) contaminated with different Cu concentrations. When lettuce was grown, similar toxic effects and accumulation values were obtained for both of the agricultural areas under analysis. In both cases, the maximum threshold value was obtained for the soil having the highest pH and clay content, independently of the soil type. When comparing both crops in the European Mediterranean soils, toxicity values calculated for tomato were higher, and translocation of Cu to the fruit was constantly low, independently of the Cu dose. Moreover, tomato showed an important phytoremediation potential, extracting Cu from not only low–medium but also from highly (>1700 mg/kg) Cu-contaminated basic agricultural soils, and having low translocation rates to fruits. The analysis of the influence of soil properties on the effect of Cu on plant biomass production led to similar conclusions in both assays. SOM, clay content and CEC are the most relevant properties affecting the dynamic of Cu in soil. Considering this, for the type of crops and soils considered, the effect of Cu on plant biomass production was the most relevant of those analysed, and pH, clay content, SOM and CEC the most relevant soil properties. Therefore, these aspects should be considered when establishing adequate soil quality standards and proposing adequate soil management practices.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"Daniel Sacristán and Ester Carbó",authors:[{id:"186105",title:"Dr.",name:"Daniel",middleName:null,surname:"Sacristán",slug:"daniel-sacristan",fullName:"Daniel Sacristán"},{id:"194070",title:"Dr.",name:"Ester",middleName:null,surname:"Carbó",slug:"ester-carbo",fullName:"Ester Carbó"}]}],mostDownloadedChaptersLast30Days:[{id:"52054",title:"Radioactive Contamination of the Soil: Assessments of Pollutants Mobility with Implication to Remediation Strategies",slug:"radioactive-contamination-of-the-soil-assessments-of-pollutants-mobility-with-implication-to-remedia",totalDownloads:8532,totalCrossrefCites:8,totalDimensionsCites:14,abstract:"Accidental releases, nuclear weapons testing, and inadequate practices of radioactive waste disposal are the principal human activities responsible for radioactive contamination as a new and global form of soil degradation. Understanding the radionuclide distribution, mobility and bioavailability, as well as the changes caused by the variation of environmental conditions, is essential for soil rehabilitation. This chapter aims to highlight the importance of evaluating radionuclide distribution, for the selection of proper in situ or ex situ remediation strategy. Attention was focused onto remediation methods based on radioactive pollutants redistribution, for enhanced separation (chemical extraction) or containment (in situ immobilization). When the excavation and off-site leaching treatments are uneconomic, impractical, or unnecessary, in situ stabilization by the addition of appropriate reactive materials is an alternative approach. The optimization of factors in control of chemical leaching methods, selection of cost-effective immobilization agents, especially among suitable wastes and by-products, and verification of long-term effects of remediating actions are the major challenges for future investigation in this field. Furthermore, the improvement and standardization of the methods for radionuclide speciation are necessary to enable comparison between studies and monitoring of the effects achieved by the soil treatments.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"Ivana Smičiklas and Marija Šljivić-Ivanović",authors:[{id:"186699",title:"Ph.D.",name:"Marija",middleName:null,surname:"Sljivic-Ivanovic",slug:"marija-sljivic-ivanovic",fullName:"Marija Sljivic-Ivanovic"},{id:"186801",title:"Dr.",name:"Ivana",middleName:null,surname:"Smičiklas",slug:"ivana-smiciklas",fullName:"Ivana Smičiklas"}]},{id:"62735",title:"Peat Use in Horticulture",slug:"peat-use-in-horticulture",totalDownloads:1522,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Peat is a spongy substance which is an effect of incomplete decomposition of plant residues in different stages of decomposition. Between the several organic matters which are used as substrate for horticultural plants cultivation in soilless conditions, peat is the unabandonable ingredient for mixtures for commercial production of plants. Peat is used in horticulture as a component of garden plant substrates, in agriculture for the production of garden soil and as an organic fertilizer, and in balneology as a material for baths and wraps. The use of peat for agriculture and horticulture is determined by the following quality parameters: the degree of decomposition, ash content, pH, the presence of carbonates, the density of the solid phase, bulk density, and porosity. As an organic material, the peat forms in the acidic, waterlogged, and sterile conditions of fens and bogs. The conditions seem like the development of mosses. The plants do not compose as they die. Instead of this, the organic matter is laid down and accumulates in a slow time as peat due to the oxygen deficiency in the bog. This makes peat a highly productive growing medium. In the present novel review, we discuss the peat use in horticulture.",book:{id:"6316",slug:"peat",title:"Peat",fullTitle:"Peat"},signatures:"Nurgul Kitir, Ertan Yildirim, Üstün Şahin, Metin Turan, Melek Ekinci,\nSelda Ors, Raziye Kul, Hüsnü Ünlü and Halime Ünlü",authors:[{id:"140612",title:"Prof.",name:"Metin",middleName:null,surname:"Turan",slug:"metin-turan",fullName:"Metin Turan"},{id:"186637",title:"Dr.",name:"Nurgül",middleName:null,surname:"Kıtır",slug:"nurgul-kitir",fullName:"Nurgül Kıtır"},{id:"186639",title:"Prof.",name:"Ertan",middleName:null,surname:"Yildirim",slug:"ertan-yildirim",fullName:"Ertan Yildirim"},{id:"247120",title:"Prof.",name:"Melek",middleName:null,surname:"Ekinci",slug:"melek-ekinci",fullName:"Melek Ekinci"},{id:"247121",title:"Prof.",name:"Selda",middleName:null,surname:"Örs",slug:"selda-ors",fullName:"Selda Örs"},{id:"247122",title:"MSc.",name:"Raziye",middleName:null,surname:"Kul",slug:"raziye-kul",fullName:"Raziye Kul"},{id:"247123",title:"Prof.",name:"Üstün",middleName:null,surname:"Şahin",slug:"ustun-sahin",fullName:"Üstün Şahin"},{id:"260571",title:"Prof.",name:"Hüsnü",middleName:null,surname:"Ünlü",slug:"husnu-unlu",fullName:"Hüsnü Ünlü"},{id:"260572",title:"Dr.",name:"Halime",middleName:null,surname:"Ünlü",slug:"halime-unlu",fullName:"Halime Ünlü"}]},{id:"59383",title:"The Status of Pachiterric Histosol Properties as Influenced by Different Land Use",slug:"the-status-of-pachiterric-histosol-properties-as-influenced-by-different-land-use",totalDownloads:1271,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Soil drainage as well as soil cultivation and fertilization has considerable influence on the organic matter mineralization rate and changes in the profile structure. Our research suggested that quantitative and qualitative characteristics of peat soil are changing in response to the renaturalization processes and different management. The study set out to estimate chemical and physical properties of Pachiterric Histosol, qualitative and quantitative changes in carbon resulting from different management and renaturalization processes. Wetland and peatland soils are among the largest organic carbon stocks, and their use contributes to carbon emissions or accumulation processes. The focus of our work is research into the peculiarities of organic carbon accumulation and transformation as influenced by different land use of peat soil. Results on the chemical properties of Pachiterric Histosol showed the influence of management and renaturalization on mobile and by pyrophosphate solution extractable humic and fulvic acids and humification degree. We are also exploring the specificities of organic carbon variation in the context of peat renaturalization and are seeking to answer the question as how to optimize the use of peat soils and how to match up this with the renaturalization processes in order to reduce greenhouse gas emissions and contribute to organic carbon accumulation and conservation in the soil.",book:{id:"6316",slug:"peat",title:"Peat",fullTitle:"Peat"},signatures:"Alvyra Slepetiene, Kristina Amaleviciute-Volunge, Jonas Slepetys,\nInga Liaudanskiene and Jonas Volungevicius",authors:[{id:"211107",title:"Dr.",name:"Alvyra",middleName:null,surname:"Slepetiene",slug:"alvyra-slepetiene",fullName:"Alvyra Slepetiene"},{id:"211216",title:"Dr.",name:"Kristina",middleName:null,surname:"Amaleviciute",slug:"kristina-amaleviciute",fullName:"Kristina Amaleviciute"},{id:"211217",title:"Dr.",name:"Jonas",middleName:null,surname:"Slepetys",slug:"jonas-slepetys",fullName:"Jonas Slepetys"},{id:"211219",title:"Dr.",name:"Inga",middleName:null,surname:"Liaudanskiene",slug:"inga-liaudanskiene",fullName:"Inga Liaudanskiene"},{id:"211221",title:"Dr.",name:"Jonas",middleName:null,surname:"Volungevicius",slug:"jonas-volungevicius",fullName:"Jonas Volungevicius"}]},{id:"62866",title:"Introductory Chapter: Introduction to Peat",slug:"introductory-chapter-introduction-to-peat",totalDownloads:1010,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"6316",slug:"peat",title:"Peat",fullTitle:"Peat"},signatures:"Bülent Topcuoğlu and Metin Turan",authors:[{id:"194133",title:"Prof.",name:"Bülent",middleName:null,surname:"Topcuoğlu",slug:"bulent-topcuoglu",fullName:"Bülent Topcuoğlu"}]},{id:"51691",title:"Contamination of Soils and Substrates in Horticulture",slug:"contamination-of-soils-and-substrates-in-horticulture",totalDownloads:2197,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Contamination of the soil environment mostly is identified with industry, especially mining and road transport. Unfortunately, also in the commercial horticulture, there are numerous problems concerning the contamination of soils and substrates. Sources of contamination can be fertilizers and waste materials polluted by heavy metals, particularly by cadmium. In the greenhouses where traditional methods of cultivation are used, the soil pollution due to the application of excessively high doses of fertilizers constitutes an environmental hazard. Much faster similar effect occurs in greenhouses where an open system of fertigation is used. In addition to mineral impurities, organic compounds emitted by the plant or that are formed during decomposition of organic matter are the problem. This phenomenon is called allelopathy. In practice, it concerns the monoculture and perennial crops and especially is observed in nurseries, orchards, plantations of berries and asparagus. For this reason, in the later section, the soil sickness, replantation problem and toxicity of mulches in green areas are also discussed.",book:{id:"5358",slug:"soil-contamination-current-consequences-and-further-solutions",title:"Soil Contamination",fullTitle:"Soil Contamination - Current Consequences and Further Solutions"},signatures:"Wlodzimierz Breś and Barbara Politycka",authors:[{id:"186184",title:"Prof.",name:"Wlodzimierz",middleName:null,surname:"Bres",slug:"wlodzimierz-bres",fullName:"Wlodzimierz Bres"},{id:"193279",title:"Prof.",name:"Barbara",middleName:null,surname:"Politycka",slug:"barbara-politycka",fullName:"Barbara Politycka"}]}],onlineFirstChaptersFilter:{topicId:"880",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:80,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:26,numberOfPublishedChapters:275,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:10,numberOfPublishedChapters:134,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:128,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:12,numberOfPublishedChapters:102,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:8,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:1,numberOfUpcomingTopics:2,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!1},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:7,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (Smart-Road: Road Damage Estimation Using a Mobile Device",doi:"10.5772/intechopen.100289",signatures:"Izyalith E. Álvarez-Cisneros, Blanca E. Carvajal-Gámez, David Araujo-Díaz, Miguel A. Castillo-Martínez and L. 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After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:"Université Grenoble-Alpes",institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly in zoonotic and vector-borne diseases (especially arboviral diseases). He is President of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as President of the Colombian Association of Infectious Diseases (ACIN). He is member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is Vicepresident of the Latin American Society for Travel Medicine (SLAMVI) and Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as Senior Researcher, Ministry of Science of Colombia. He is Professor of the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also Professor of the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. He has been awarded in 2021 with the “Raul Isturiz Award” Medal of the API. Also, in 2021, awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions on COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158026/images/system/158026.jfif",biography:"Prof. Dr. Shailendra K. Saxena is the vice dean and Professor at King George\\'s Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various prestigious international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence"},{id:"23",title:"Computational Neuroscience",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. Particularly interesting are models of various types of more compound functions and abilities, various and more general fundamental principles (e.g., regarding architecture, organization, learning, development, etc.) found at various spatial and temporal levels.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness"},{id:"24",title:"Computer Vision",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"February 18th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:98,numberOfPublishedBooks:8,editor:{id:"38652",title:"Dr.",name:"Rita",middleName:null,surname:"Payan-Carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},subseries:[{id:"19",title:"Animal Science",keywords:"Animal Science, Animal Biology, Wildlife Species, Domesticated Animals",scope:"The Animal Science topic welcomes research on captive and wildlife species, including domesticated animals. The research resented can consist of primary studies on various animal biology fields such as genetics, nutrition, behavior, welfare, and animal production, to name a few. Reviews on specialized areas of animal science are also welcome.",annualVolume:11415,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:"Universidade Paulista",institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:null,institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",annualVolume:11416,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",fullName:"Alfredo J. Escribano",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGnzQAG/Profile_Picture_1633076636544",institutionString:"Consultant and Independent Researcher in Industry Sector. Spain",institution:null},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",fullName:"Amlan Patra",profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",institutionString:"West Bengal University of Animal and Fishery Sciences",institution:{name:"West Bengal University of Animal and Fishery Sciences",institutionURL:null,country:{name:"India"}}},{id:"216995",title:"Prof.",name:"Figen",middleName:null,surname:"Kırkpınar",fullName:"Figen Kırkpınar",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRMzxQAG/Profile_Picture_1625722918145",institutionString:null,institution:{name:"Ege University",institutionURL:null,country:{name:"Turkey"}}}]},{id:"28",title:"Animal Reproductive Biology and Technology",keywords:"Animal Reproduction, Artificial Insemination, Embryos, Cryopreservation, Conservation, Breeding, Epigenetics",scope:"The advances of knowledge on animal reproductive biology and technologies revolutionized livestock production. Artificial insemination, for example, was the first technology applied on a large scale, initially in dairy cattle and afterward applied to other species. Nowadays, embryo production and transfer are used commercially along with other technologies to modulate epigenetic regulation. Gene editing is also emerging as an innovative tool. This topic will discuss the potential use of these techniques, novel strategies, and lines of research in progress in the fields mentioned above.",annualVolume:11417,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",institutionString:"The National Institute for Agricultural and Veterinary Research. 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