Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues.
An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biomedical Research on Alcoholism, Université René-Descartes, Paris, France.
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R
Nordmann
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Ribière
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Rouach
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002310:Cardiomyopathy, Alcoholic / Q000503:physiopathology; D000431:Ethanol / Q000493:pharmacokinetics*; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D013737:Testis / Q000187:drug effects
D005609:Free Radicals; D000431:Ethanol