Vitamin E: The generic term "vitamin E" refers to at least eight structural isomers of tocopherol, among which is alpha-tocopherol, the best know isomer and the one processing the most potent antioxidant activity. Vitamin E is the most widely distributed antioxidant in nature and is found in both the plant and animal kingdoms.

As the major lipid soluble antioxidant present in all cellular membranes, vitamin E protects against lipid peroxidation. Vitamin E acts directly with a variety of oxy radicals, superoxide radical, and singlet oxygen. Vitamin E can protect against some of the symptoms of selenium deficiency and vice versa. Vitamin E is the major free radical chain terminator in the lipophilic environment. The lipid solubility of tocopherol may explain why high levels are found in adrenal gland, heart, gonadal, and liver tissues. By reacting with lipid peroxyl and alkoxyl radicals, vitamin E is able to effectively protect against membrane lipid peroxidation. The sparing and synergistic actions appear to be the result of the ability of both tocopherol and selenium-dependent glutathione to decrease the production of lipid peroxidation products (Machlin, 1980; Machlin and Bendich, 1987; Yu, 1994).

Vitamin C (ascorbic acid): In contrast to vitamin E, vitamin C is water soluble and functions more effectively in an aqueous environment. Vitamin C and E work synergistically in quenching free radicals and singlet oxygen. Vitamin C also regenerates the reduced antioxidant form of vitamin E; one of its major functions may well be torecycle oxidized vitamin E.

As a reducing and antioxidant agent, ascorbic acid reacts directly with superoxide and hydroxyl free radicals and various lipid hydroperoxides. Vitamin C, when compared with other water-soluble antioxidants, provides the most effective protection against plasma lipid peroxidation. Ascorbic acid acts as both an antioxidant and a prooxidant.

As an antioxidant, vitamin C has a sparing effect on the antioxidant actions of vitamin E and selenium. Excessive amounts of vitamin C may act as a prooxidant in the presence of the transition metals iron (Fe++) and copper (Cu++) by generating cofactors of activated oxygen radicals during the promotion of lipid peroxidation.

Ascorbic acid has a dichotomous action in the body. Ascorbate's prooxidant action, which may induce lipid peroxidation, resides in its ability to reduce Fe+++ to the Fe++. The Fe++ state is known to be a potent free-radical inducer. Ascorbate is also able to induce oxidative modification of DNA bases. Laboratory studies have shown that ascorbate enhances lipid peroxidation in the microsomes of animals deficient in vitamin E but suppresses it in animals having normal amounts of vitamin E. Apparently the concentration and subcellular localization of vitamin C are important factors in the dichotomization of ascorbic acid. For further information on vitamin C, see Szent-Gyorgyi (1954), Pauling (1970), King and Burns (1975), Cameron and Pauling (1984), and Gordon (1996).

Vitamin A (carotenoids): Beta-carotene, an efficient biological antioxidant, is considered to be the most efficient quencher of singlet oxygen. Although beta-carotene is the major carotenoid precursor of vitamin A, vitamin A does not quench singlet oxygen and is said to have a very small capability of scavenging free radicals. Carotenoids protect lipids against peroxidation by quenching free radicals and other reactive species. Beta-carotene traps free radicals through its inhibition of lipid peroxidation induced by the xanthine oxidase system.

Beta-carotene, like vitamin C, seems to function as both an antioxidant and a prooxidant. Under low O2 partial pressures, beta-carotene exhibits excellent radical-scavenging activity. At higher oxygen partial pressures, its capacity to trap free radicals shows autocatalytic prooxidant effects, with concomitant loss of its antioxidant activity (Ames, 1983; Yu et al,. 1994).

Glutathione (GSH): The tripeptide-reduced glutathione (y0glutamyl-cysteine-clycine) is the most abundant low-molecular-weight thiol present in almost all mammalian cellular systems. Reduced glutathione is characterized by its reactive thiol group and its y-glutamyl bond, which makes it resistant to peptidase attack. The versatility of glutathione is due to its chemical properties that allow it to serve as both a nucleophile and an effective reductant by interacting with numerous eletrophilic and oxidizing compounds such as hydrogen peroxide, superoxide, and hydroxyl free radicals.

Glutathione plays an effective reductant role in a variety of detoxification processes. This is evidenced, for example, by glutathione depletion as it nullifies the damage caused by peroxide, such as its ability to increase the susceptibility of animals to cytotoxicity and affect drug interventions in neoplastic diseases (Al-Turk et al., 1987).

Glutathione readily interacts with free radicals, especially hydroxyl and carbon radicals, by donating a hydrogen atom. Reactions of this type provide protection by neutralizing reactive hydroxyl radicals which are a major source of free radical pathology, including cancer.

Endogenous glutathione can repair single strand breaks in the DNA molecule up to one hour after exposure to ionizing radiation. This ability is probably due to the role of glutathione in the synthesis of the DNA molecule (Holmgren, 1979). Glutathione affects radiation sensitivity by its ability to scavenge radiation-induced free radicals as well as restore radiation-damaged molecules by hydrogen donation.

Most antioxidant defenses, including glutathione, fluctuate under various physiological conditions, neoplastic diseases, and aging (Ames, 1983; Levine and Kidd, 1994).

Under such conditions, any reduction in glutathione levels may suggest the need for nutritional supplementation of free amino acids and glutathione. Reduced glutathione is available as a food supplement.

Uric Acid: In the past, uric acid was generally looked upon as merely an end product of purine metabolism. More recently, uric acid has become increasingly recognized as an important biological antioxidant. Scientific studies have demonstrated that uric acid is a potent physiological antioxidant, playing a major role in both extracelluar and intracellular defense mechanisms. Although the precise biochemical mechanism is not completely determined, uric acid appears to have a sparing action in plasma ascorbate, probably by complexing transition metals such as iron and copper. Furthermore, uric acid may serve as an important protective agent of the overall defense systems, thus helping to increase the life span of the individual (Ames, 1983; Yu, 1994).