**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

**5**

**3. Antioxidants**

*Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

**2.3 Oxidative damage to DNA**

**Figure 2.**

*et al. [1].*

tion of cancer and accelerated aging (**Figure 2**) [1, 5, 9].

oxidized intermediates, which does not affect food quality [11].

**2.4 Oxidative damage to carbohydrates**

as indicators in lipid peroxidation assay, and have been confirmed in diseases including neurogenerative diseases, heart disease, and diabetes (**Figure 2**) [1, 8].

*A schematic diagram illustrating the detrimental effects of free radicals on biomolecules. Adapted from Law* 

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 causa-

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•

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

, forming

*Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

#### **Figure 2.**

*Antioxidants*

**Figure 1.**

*and Rizvi [5].*

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**) [3–5]. 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.

*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* 

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

Lipids have an important structural and functional role in cell membranes. After

[7]. Because of lipid peroxidation, several compounds are produced,

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 polyunsatu-

such as alkanes, malondialdehyde, and isoprostanes. These compounds are utilized

**4**

rated is OH•

**2. Oxidative stress**

**2.1 Oxidative damage to proteins**

of cataracts and aging (**Figure 2**) [1, 6].

**2.2 Oxidative damage to lipids**

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

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) [12–14].

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].


**7**

derivatives.

*Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

thiophosphate.

bifunctional compounds.

with hydroperoxide.

a.Natural antioxidants

phenolic in structure and include the following:

lism functions such as, vitamin C, E, and B.

[19, 20].

3.Based on solubility, antioxidants can be classified as water-soluble or lipidsoluble antioxidants. Vitamin C is a type of water-soluble vitamin found in

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.

a.Antioxidants that are able to break chains through reacting with peroxyl radicals containing weak O–H or N–H bonds, phenol, naphthol, hydroqui-

b.Antioxidants with a capability to break chains by reacting with alkyl

c.Antioxidants that terminate cyclic chain such as aromatic amines, nitroxyl

d.Hydroperoxide decomposing antioxidants such as sulfide, phosphide, and

e.Metal-deactivating antioxidants include diamines, hydroxyl acids, and

f. Synergism action of a number of antioxidants including phenol sulfide in which the phenolic group reacts with the peroxylradical's sulfide group

6.Based on their occurrence, antioxidants are categorized as natural or synthetic

They are classified as chain-breaking antioxidants, which react with radicals and convert them into more stable products. Generally, antioxidants of this group are

1.Antioxidant minerals: these are antioxidant enzymes cofactors like selenium, copper, iron, zinc, and manganese. Absence of the cofactors will definitely

2.Antioxidant vitamins: these are important and required for most body metabo-

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

enhance many macromolecules metabolism such as carbohydrates.

cellular fluids such as cytosol or cytoplasmic matrix.

5.Kinetically antioxidants can be categorized as below:

none, aromatic amines, and aminophenols.

radicals: quinines, nitrones, and iminoquinones.

radicals, and variable valence metal compounds.

*Antioxidants*

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

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) [12–14].

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].

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

positive effect on gene expression [7].

**4. Antioxidant categories**

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

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

molecule to polymer and complicated bio-system [8].

**6**

reactions.

	- a.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.
	- b.Antioxidants with a capability to break chains by reacting with alkyl radicals: quinines, nitrones, and iminoquinones.
	- c.Antioxidants that terminate cyclic chain such as aromatic amines, nitroxyl radicals, and variable valence metal compounds.
	- d.Hydroperoxide decomposing antioxidants such as sulfide, phosphide, and thiophosphate.
	- e.Metal-deactivating antioxidants include diamines, hydroxyl acids, and bifunctional compounds.
	- f. Synergism action of a number of antioxidants including phenol sulfide in which the phenolic group reacts with the peroxylradical's sulfide group with hydroperoxide.

a.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:


b.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]. ⎯

$$\text{O}\_2^- \star \text{O}\_2^- \star 2\text{H}^+ \xrightarrow{\text{SOD}} \text{H}\_2\text{O}\_2 + \text{O}\_2 \tag{1}$$

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 [26–28].

Extracellular SOD (ECSOD) is a tetrameric protein, containing Cu and Zn having a high affinity for certain glycosaminoglycans such as heparin and heparin

**9**

*Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

liberating from the endothelium by O2

vascular functions during aging [29].

*4.1.1.1 Application*

tation caused by UV rays.

*4.1.2 Catalase (CAT)*

red blood cells.

*4.1.2.1 Application*

provides an adequate supply of SOD [3].

with the deficiency or mutation of CAT enzyme [30, 31].

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

•

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

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 pigmen-

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

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

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

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,

¯ through diffusion to smooth muscle, thus

#### *Antioxidant Categories and Mode of Action DOI: http://dx.doi.org/10.5772/intechopen.83544*

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*

*Antioxidants*

b.Synthetic antioxidants

**4.1 Antioxidant enzymes**

Se, Fe, Cu, Zn, and Mn [21].

of CAT or GPX [22, 23].

O2

of antioxidant defense [25].

− + O2 − + 2H<sup>+</sup>

especially significant for compartmentalized redox signaling [24].

kines, while oxidants moderately influenced it [26–28].

*4.1.1 Superoxide dismutase (SOD)*

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).

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

Irwin Fridovitch of Duke University and Joe McCord discovered antioxidant

⎯

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

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

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 cyto-

Extracellular SOD (ECSOD) is a tetrameric protein, containing Cu and Zn having a high affinity for certain glycosaminoglycans such as heparin and heparin

SOD→H2O2 <sup>+</sup> O2 (1)

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

**8**

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].
