FREE-RADICALS, OXIDATIVE STRESS AND ANTIO XIDANT VITAMINS

Free radicals having oxidizing properties are produced in vivo. The mo noelectronic reduction of dioxygen generates the superoxide radical (. O2-) which, according to the experimental conditions, behaves as a red ucing or an oxidizing agent. Its dismutation catalyzed by superoxide d ismutases (SODs) produces hydrogen peroxide. The latter reacting with .O2- in the presence of << redox-active >> iron produces highly aggres sive prooxidant radicals, such as the hydroxyl radical (.OH). This pro duction is prevented through intracellular enzymes (catalase and gluta thione peroxidases) which destroy the hydrogen peroxide involved in th e biosynthesis of .OH. An increase in SODs activity without parallel e nhancement of the enzymes destroying H2O2 may lead to important cellul ar disturbances. Other enzymes acting with glutathione as substrate (e specially glutathione S-transferases) contribute to the antioxidant de fence. The same holds true for selenium and zinc which act mainly thro ugh their involvement in the structure of both antioxidant enzymes and nonenzymatic proteins. Another line of antioxidant defence is represe nted by substrates acting as chain-breaking antioxidants in destructiv e processes linked to prooxidant free radicals, such as lipid peroxida tion. The main membranous antioxidant is alpha-tocopherol which is abl e to quench efficiently lipid peroxyl radicals. Its efficiency would b e quickly exhausted if the tocopheryl radical formed during this react ion wouldn't be retransformed into alpha-tocopherol through the interv ention of ascorbate and/or glutathione. Ubiquinol and dihydrolipoate a lso contribute to the membranous antioxidant defence, whereas caroteno ids are mainly responsible for the prevention of the deleterious effec ts of singlet oxygen. An oxidative stress is apparent when the antioxi dant defence is insufficient to cope with the prooxidant production. I t may elicit many intracellular disturbances, affecting mainly lipids or proteins. The contributive role of such an oxidative stress has bee n considered in many pathological conditions. As an example, the mecha nisms leading to such a stress in the liver and in some extra-hepatic tissues during alcohol intoxication are shortly described.