addition, exposure to UV radiation or to air pollutants such as cigarette smoke (which contains oxidants) or ozone can cause the body to increase the levels of reactive radical species.

ROS is a collective term that includes several oxygen radicals—superoxide (O2·-) and its protonated form, hydroperoxyl (HO2·), hydroxyl (OH·), peroxyl (RO2·), alkoxyl (RO·)—and nonradicals—hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3), and singlet oxygen (1O2)—that are oxidizing agents or are easily converted into radicals. RNS includes nitric oxide (NO·), peroxynitrite (ONOO-), and peroxynitrous acid (ONOOH). Various compounds in the human body generate free radicals in their metabolism. Examples are catecholamines and compounds found in the mitochondrial electron-transport chain.

In addition, activated phagocytes produce ROS as one of the defense mechanisms they use to kill microbes. Thus, in this situation, ROS are used by the body as a defense mechanism against infection.

An imbalance of oxidants and antioxidants resulting in increased levels of ROS, RNS, or both can result in damage to lipids, proteins, carbohydrates, and DNA. A considerable body of biological evidence shows that ROS and RNS can damage cells and other body components and could in theory contribute to dysfunction and disease states. It has been postulated that oxidative damage caused by increased levels of production of ROS or RNS may contribute to the development of many chronic diseases, including age-related eye disease, atherosclerosis, cancer, coronary heart disease, diabetes, inflammatory bowel disease, neurodegenerative diseases, respiratory disease, and rheumatoid arthritis.

Antioxidant Mechanisms

The mechanisms of antioxidant action for decreasing the adverse effects of ROS or RNS are varied. They include (1) decreasing ROS or RNS formation; (2) binding metal ions needed for catalysis of ROS generation; (3) scavenging ROS, RNS, or their precursors; (4) up-regulating endogenous antioxidant enzyme defenses; (5) repairing oxidative damage to biomolecules, such as glutathione peroxidases or specific DNA glycosylases; and (6) influencing and up-regulating repair enzymes. Some antioxidants remove free radicals by reacting directly with them in a noncatalytic manner before the radicals react with other cell components. For example, vitamin E inhibits lipid peroxidation by scavenging radical intermediates in the radical chain reaction with polyunsaturated fatty acids. The effectiveness of each dietary antioxidant depends on which ROS or RNS is being scavenged, how and where they are generated, the accessibility of the antioxidants to this site, and what target of damage, or oxidizable substrate, is involved.

Antioxidant defense mechanisms include not only low-molecular-weight compounds, but also some antioxidant defense systems in the human body that



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