Oxidants and Antioxidants. Biological Effects and Therapeutic Perspectives
Urban T; Hurbain I; Urban M; ClŽment A; Housset B
Service de Pneumologie et Laboratoire de Physiopathologie
Pulmonaire, Hospital - Saint-Antoine et Faculty Saint-Antoine,
Paris.
Ann Chir, 49: 5, 1995, 427-34
Abstract:
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.