**5.5 Prevention of DNA damage**

*Antioxidants*

Fe2+ (or Cu<sup>+</sup>

radical (formed via Cu<sup>+</sup>

lular oxygen, forming O2

O2

promote O2

oxidative stress-related diseases [3].

**5.4 Prevention of lipid peroxidation**

Fe3+ (or Cu2+) <sup>+</sup> vit <sup>C</sup> <sup>H</sup><sup>−</sup>

**5.3 Free radical generating enzyme inhibitors**

reactive and can directly react with proteins and lipids to produce carbonyls (aldehydes and ketones), cross linking, and lipid peroxidation. Chelating metal ions are

) <sup>+</sup> H2O2 Fe3+ (or Cu2+) <sup>+</sup> OH•

Fe2+ (or Cu<sup>+</sup>

Cu2+/ascorbic acid) extremely efficiently and prevent the damage of DNA by OH•

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 extracel-

through catalyzing the oxidation of hypoxanthine and xanthin to uric acid yielding

•¯ and H2O2 and increase the oxidation level in an organism [63]. In addition, O2

•¯ generation as well as the development of new therapeutic agents for

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

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

•¯ [62]. Uric acid is formed by xanthin oxidase enzyme

<sup>+</sup> OH<sup>−</sup>

) + vitamin C−•

(2)

•¯

•¯

+ H<sup>+</sup> (3)

(formed in situ with

able to decrease their action, thus reducing the ROS formation.

Studies showed that Se antioxidant is able to chelate Cu<sup>+</sup>

/H2O2) [3].

**16**

*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].
