[Alcohol and free radicals: from basic research to clinical prospects].
An oxidative stress occurs in the liver of rats following various conditions of ethanol administration. The ethanol-inducible cytochrome P450 2E1 plays a key role in its generation, favoured itself by an increase in the "redox-active" fraction of intracellular non-heme iron. Administration of ethanol elicits the generation of the 1-hydroxyethyl radical, 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 administration associated with a high fat diet. The severity of these disorders is correlated to the intensity of the oxidative stress. Some conditions of ethanol administration to rats also elicit an oxidative stress in the myocardium and central nervous system. Through its inhibitory effect on glutamine synthetase activity and resulting excitotoxicity it may contribute to neuronal death and possibly to dependence on alcohol. Disorders related to an oxidative stress were also reported in the serum and erythrocytes as well 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 vitamin E may be considered in the prevention of severe cellular disorders in individuals consuming large amounts of alcoholic beverages. An increase in free radical production is likely playing a role in the induction of severe cellular damage linked to repeated withdrawals occurring as a result of heavy and sporadic ethanol intake.
Nordmann
R
R
Biomécicale des Saints-Pères, PARIS.
Rouach
H
H
D000437:Alcoholism / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; C065424:1-hydroxyethyl radical; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1
Alcool et radicaux libres: de la recherche fondamentale aux espoirs cliniques.