Oxidative stress induced by ethanol in rat hepatocyte cultures.
Many controversies still exist with regard to the relationship between alcoholic intoxication and the occurrence of an oxidative stress. To attempt to resolve this question, first we investigated the induction by acute ethanol intoxication of lipid peroxidation in primary rat hepatocyte cultures using simultaneously two indices for each sample. When considering conjugated-diene indice, any lipid peroxidation elevation could be observed, whereas a net increase of extracellular free malondialdehyde was noted at 5 hours of incubation. These results led us to estimate the intracellular pool of low molecular weight iron which is known to be the iron species catalytically active in hydroperoxide degradation. An early enhancement of +20-30% of cellular low molecular weight iron was observed. Thus the discrepancy between conjugated dienes and malondialdehyde could be ascribed to an increase of hydroperoxide degradation into malondialdehyde by the transient cellular pool of low molecular weight iron. Lipid peroxidation and low molecular weight iron augmentation were linked to ethanol metabolism, since both were suppressed by the addition of 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Superoxide dismutase activity was increased in the early incubation time (1 hour) and then markedly reduced. We conclude that ethanol metabolism can induce a lipid peroxidation accompanied by an elevation of intracellular pool of low molecular weight iron and a decrease of superoxide dismutase activity.
Sergent
O
O
Laboratoire de Biologie Cellulaire et Végétale, INSERM U49, UFR des Sciences Pharmaceutiques, Rennes, France.
Morel
I
I
Chevanne
M
M
Cillard
P
P
Cillard
J
J
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D000077604:Fomepizole; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008970:Molecular Weight; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D018384:Oxidative Stress; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D011720:Pyrazoles; D014810:Vitamin E; D000431:Ethanol; D008315:Malondialdehyde; D000077604:Fomepizole; D007501:Iron; D000426:Alcohol Dehydrogenase; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase