ALCOHOL AND FREE-RADICALS - FROM BASIC RE SEARCH TO CLINICAL PROSPECTS

An oxidative stress occurs in the liver of rats following various cond itions of ethanol administration. The ethanol-inducible cytochrome P45 0 2E1 plays a key role in its generation, favoured itself by an increa se in the ''redox-active'' fraction of intracellular non-heme iron. Ad ministration of ethanol elicits the generation of the I-hydroxyethyl r adical, which has been identified in vivo. Its reactivity contributes to alcohol-induced immunological disturbances. Liver inflammatory and fibrotic disorders can be reproduced in rats by long-term ethanol admi nistration associated with a high fat diet. The severity of these diso rders is correlated to the intensity of the oxidative stress. Some con ditions of ethanol administration to rats also elicit an oxidative str ess in the myocardium and central nervous system. Through its inhibito ry effect on glutamine synthetase activity and resulting excitotoxicit y it may contribute to neuronal death and possibly to dependence on al cohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as weil as in liver biopsies from alcoholic individuals. Their detection may be useful to follow the evolution of alcoholic liver diseases. Supplementation with antioxidants such as v itamin E may be considered in the prevention of severe cellular disord ers in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the in duction of severe cellular damage linked to repeated withdrawals occur ring as a result of heavy and sporadic ethanol intake.