title: Implication of free radical mechanisms in ethanol-induced cellular injury.
abstract: Numerous experimental data reviewed in the present article indicate that free radical mechanisms contribute to ethanol-induced liver injury. Increased generation of oxygen- and ethanol-derived free radicals has been observed at the microsomal level, especially through the intervention of the ethanol-inducible cytochrome P450 isoform (CYP2E1). Furthermore, an ethanol-linked enhancement in free radical generation can occur through the cytosolic xanthine and/or aldehyde oxidases, as well as through the mitochondrial respiratory chain. Ethanol administration also elicits hepatic disturbances in the availability of non-safely-sequestered iron derivatives and in the antioxidant defense. The resulting oxidative stress leads, in some experimental conditions, to enhanced lipid peroxidation and can also affect other important cellular components, such as proteins or DNA. The reported production of a chemoattractant for human neutrophils may be of special importance in the pathogenesis of alcoholic hepatitis. Free radical mechanisms also appear to be implicated in the toxicity of ethanol on various extrahepatic tissues. Most of the experimental data available concern the gastric mucosa, the central nervous system, the heart, and the testes. Clinical studies have not yet demonstrated the role of free radical mechanisms in the pathogenesis of ethanol-induced cellular injury in alcoholics. However, many data support the involvement of such mechanisms and suggest that dietary and/or pharmacological agents able to prevent an ethanol-induced oxidative stress may reduce the incidence of ethanol toxicity in humans.
authors.affiliation: Department of Biomedical Research on Alcoholism, University René Descartes (Paris V), France.
authors.forename: R
authors.initials: R
authors.lastname: Nordmann
authors.forename: C
authors.initials: C
authors.lastname: Ribière
authors.forename: H
authors.initials: H
authors.lastname: Rouach
mesh_terms: D000818:Animals; D005609:Free Radicals; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005609:Free Radicals