[Oxidants and antioxidants. Biological effects and therapeutic perspectives]

The main oxidizing free radicals (FR) are oxygen-derived metabolites (superoxide anion O2-, hydrogen peroxide H2O2, hydroxyl radical OH (zero)), hypochloric acid, chloramines, nitrogen dioxide, ozone and lipid peroxides. They are produced continually by living organisms, either in the intracellular compartment by the mitochondrial respiratory chain and mixed function oxidase system, or in the extracellular compartment, especially by phagocytes. The body possesses complex protective antioxidant systems against this potentially toxic production, such as dismutase superoxides, catalase, the glutathione enzyme system, metallic ion sequestration, enzymes degrading proteins injured by FR, metabolising hydroperoxides, and repairing DNA, and vitamins E, C, P, and betacarotene. A physiological steady-state is established under normal conditions between the production of oxidants and their neutralization by antioxidants. Oxidative lesions result from a disturbance of the oxidant-antioxidant balance. Oxygen-derived metabolites act on polyunsaturated cell membrane lipids, induce genetic alterations, and oxidize sulfhydryl groups of proteins, thereby modifying their functions. FR are involved in major physiological mechanisms such as phagocytosis, the inflammatory reaction, and the reperfusion ischaemia phenomenon observed during organ storage. The therapeutic use of enzymatic (SOD, catalase, GSH) and nonenzymatic antioxidants (vitamins E, N-acetylcysteine, allopurinol and oxypurinol) has yet to be evaluated. The current state of our knowledge indicates the extreme complexity of these systems and calls for caution in the therapeutic use of antioxidant substances.