**2.2 Physiological and physiopathological processes related to free radicals (FR)**

The human body responds to oxidative stress with antioxidant defense, but in certain cases, it may be insufficient, triggering different physiological and physiopathological processes. Currently, many processes are identified related to the production of free radicals. Among them are mutagenesis, cell transformation, cancer, arteriosclerosis, myocardial infarction, diabetes, inflammatory diseases, central nervous system disorders, and cell aging [10, 11].

**27**

**Figure 3.**

*Reaction of hydroxyl radical with sugar [8].*

*Antioxidant Compounds and Their Antioxidant Mechanism*

*DOI: http://dx.doi.org/10.5772/intechopen.85270*

*Reaction mechanism of superoxide radical.*

*Reaction of hydroxyl radical with polyunsaturated fatty acids.*

**Figure 1.**

**Figure 2.**

*Antioxidant Compounds and Their Antioxidant Mechanism DOI: http://dx.doi.org/10.5772/intechopen.85270*

$$\begin{array}{ccccccccccccc} \mathbf{O\_{z}^{\bullet \bullet}} & \star & \mathsf{H}\mathbf{O\_{z}^{\bullet}} & \star & \mathsf{H^{\bullet}} & \star & \mathsf{H^{\bullet}}\mathbf{O\_{z}^{\bullet}} & \star & \mathsf{O\_{z}} \\ & & & & \mathsf{H}\mathbf{O\_{z}^{\bullet}} & \star & \mathsf{H}\mathbf{O\_{z}^{\bullet}} & \star & \mathsf{H^{\bullet}}\mathbf{O\_{z}^{\bullet}} & \star & \mathsf{O\_{z}} \\ \mathbf{O\_{z}^{\bullet}} & \star & \mathsf{O\_{z}}^{\bullet} & \star & \mathsf{H^{\bullet}}\mathsf{H^{\bullet}} & \star & \mathsf{H^{\bullet}}\mathsf{H^{\bullet}} & \star & \mathsf{O\_{z}} \\ \end{array}$$

#### **Figure 1.**

*Antioxidants*

O2

HO2

NO•

CO3

**Table 1.**

ONOOCO2

Free radicals produce diverse actions on the metabolism of immediate principles,

1.In the polyunsaturated lipids of membranes, producing loss of fluidity and cell

2.In the glycosides, altering cellular functions such as those associated with the activity of interleukins and the formation of prostaglandins, hormones, and

4.In nucleic acids, by modifying bases (**Figure 5**) [8], producing mutagenesis

The human body responds to oxidative stress with antioxidant defense, but in certain cases, it may be insufficient, triggering different physiological and physiopathological processes. Currently, many processes are identified related to the production of free radicals. Among them are mutagenesis, cell transformation, cancer, arteriosclerosis, myocardial infarction, diabetes, inflammatory diseases,

3.In proteins, producing inactivation and denaturation (**Figure 4**) [9].

**2.2 Physiological and physiopathological processes related to free** 

central nervous system disorders, and cell aging [10, 11].

which can be the origin of cell damage [7]:

neurotransmitters (**Figure 3**) [8].

and carcinogenesis.

**radicals (FR)**

lysis because of lipid peroxidation (**Figure 2**).

**Specie Source Function**

metal-catalyzed Fenton reaction

ONOO• Reaction of O2 with NO• ONOO•

superoxide dismutase (SOD)-

•−

obtained by reaction of ONOO<sup>−</sup> with

<sup>−</sup> The peroxynytrite-CO2 adduct is

react with bicarbonate to

arginine as a substrate and NADPH as

reaction, and nonenzymatic electron

•<sup>−</sup> HO2

through the

−

•

carbohydrates

in blood vessels

nitroguanine

and nucleic acids

CO3

α-tocopherol in plasma

HO•

NO•

It can act as reducing agent of iron complexes such as cytochrome-c or oxidizing agent to oxidize ascorbic acid and α-tocopherol

initiates fatty acid peroxidation

 reacts with both organic and inorganic molecules including DNA, proteins, lipids, and

 is an intracellular second messenger stimulates guanylate cyclase and protein kinases and helps in smooth muscle relaxation

 is a strong oxidizing and nitrating species of methionine and tyrosine residues in proteins and oxidizes DNA to form

•<sup>−</sup> oxidizes biomolecules such as proteins

This anion promotes nitration of tyrosine fragments of the oxyhemoglobin via FR

This radical acts on the antioxidative mechanism decreasing ascorbate and

•<sup>−</sup> Enzymatic process, autoxidation

transfer reactions

NO• Action of nitric oxide-synthase using

an electron source

•<sup>−</sup> The intermediate of reaction

generates CO3

Cu2+-OH•

CO2

*Free radicals (FR) generated in biological systems.*

<sup>2</sup> Protonation of ONOO<sup>−</sup> or homolytic fragmentation of ONOOCO2

• Protonation of O2

HO• H2O2 generates HO•

**26**

*Reaction mechanism of superoxide radical.*

**Figure 2.** *Reaction of hydroxyl radical with polyunsaturated fatty acids.*

**Figure 3.** *Reaction of hydroxyl radical with sugar [8].*

**Figure 4.** *Reaction of hydroxyl radical with α-aminoacids [9].*

**29**

**3.3 Repair system**

*Antioxidant Compounds and Their Antioxidant Mechanism*

nonenzymatic, as well as being a system for repairing molecules.

Biological systems in oxygenated environments have developed defense mechanisms, both physiological and biochemical. Among them, at the physiological level, is a microvascular system with the function of maintaining the levels of O2 in the tissues, and at a biochemical level, the antioxidant defense can be enzymatic or

Aerobic organisms have developed antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and DT-diaphorase. SOD is responsible for the dismutation reaction of O2 to H2O2, which in subsequent reactions, catalyzed by catalase or by GPx, is converted into H2O and O2. SOD is the most important and most powerful detoxification enzyme in the cell. SOD is a metalloenzyme and, therefore, requires a metal as a cofactor for its activity. Depending on the type of metal ion required as a cofactor by SOD, there are several forms of the enzyme [12, 13]. CAT uses iron or manganese as a cofactor and catalyzes the degradation or reduction of hydrogen peroxide (H2O2) to produce water and molecular oxygen, thus completing the detoxification process initiated by SOD [14, 15]. CAT is highly efficient at breaking down millions of H2O2 molecules in a second. CAT is mainly found in peroxisomes, and its main function is to eliminate the H2O2 generated during the oxidation of fatty acids. GPx is an important intracellular enzyme that breaks down H2O2 in water and lipid peroxides in their corresponding alcohols; this happens mainly in the mitochondria and sometimes in the cytosol [16]. The activity of GPx depends on selenium. In humans, there are at least eight enzymes GPx, GPx1–GPx8 [17]. Among glutathione peroxidases, GPx1 is the most abundant selenoperoxidase and is present in virtually all cells. The enzyme plays an important role in inhibiting the process of lipid peroxidation and, therefore, protects cells from oxidative stress [18]. Low GPx activity leads to oxidative damage of the functional proteins and the fatty acids of the cell membrane. GPx, particularly GPx1, has been implicated in the development and prevention of many diseases, such as cancer and cardiovascular diseases [19]. DT-diaphorase catalyzes the reduction of quinone to quinol and participates in the reduction of drugs of quinone structure [20]. DNA regulates the production of these enzymes in cells.

This system of antioxidants consists of antioxidants that trap FR. They capture FR to avoid the radical initiation reaction. Neutralize the radicals or capture them by donating electrons, and during this process, the antioxidants become free radicals, but they are less reactive than the initial FR. FR from antioxidants are easily neutralized by other antioxidants in this group. The cells use a series of antioxidant compounds or free radical scavengers such as vitamin E, vitamin C, carotenes, ferritin, ceruloplasmin, selenium, reduced glutathione (GSH), manganese, ubiquinone, zinc, flavonoids, coenzyme Q, melatonin, bilirubin, taurine, and cysteine. The flavonoids that are extracted from certain foods interact directly with the reactive species to produce stable complexes or complexes with less reactivity, while in other foods, the flavonoids

perform the function of co-substrate in the catalytic action of some enzymes.

Enzymes that repair or eliminate the biomolecules that have been damaged by ROS, such as lipids, proteins, and DNA, constitute the repair systems. Common

*DOI: http://dx.doi.org/10.5772/intechopen.85270*

**3. Role of antioxidants**

**3.1 Primary enzymatic system**

**3.2 Nonenzymatic system**

**Figure 5.** *Reaction of hydroxyl radical with the basepair of DNA guanosine [8].*
