Acetaldehyde involvement in ethanol-induced potentiation of rat hepatocyte damage due to the carcinogen 1,2-dibromoethane.
Previous experiments with hepatocytes isolated from ethanol-treated rats showed that alcohol potentiates the toxic action of 1,2-dibromoethane (DBE) by inhibiting its metabolism via glutathione-S-transferase. The aim of this study was to investigate whether acetaldehyde, the main product of ethanol metabolism, may be responsible for such inactivation. By pretreatment with 4-methylpyrazole, an inhibitor of acetaldehyde formation, the ethanol inactivation of glutathione transferase was actually prevented. As a consequence of this protective action, 4-methylpyrazole also prevented the high basal lipid peroxidation and the potentiated DBE toxicity observed in hepatocytes from ethanol-dosed animals. Finally, the inactivation of glutathione-S-transferase by concentrations of acetaldehyde likely to occur in the ethanol-intoxicated animal was confirmed in an in vitro model by direct aldehyde addition to hepatocyte suspensions.
Chiarpotto
E
E
Department of Experimental Medicine and Oncology, University of Turin, Italy.
Biasi
F
F
Scavazza
A
A
Camandola
S
S
Aragno
M
M
Tamagno
E
E
Danni
O
O
Dianzani
M U
MU
Poli
G
G
D000079:Acetaldehyde / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004357:Drug Synergism; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D015946:Ethylene Dibromide / Q000633:toxicity*; D000077604:Fomepizole; D005982:Glutathione Transferase / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002273:Carcinogens; D011720:Pyrazoles; D015946:Ethylene Dibromide; D000431:Ethanol; D000077604:Fomepizole; D005982:Glutathione Transferase; D000079:Acetaldehyde