The metabolism of acetaldehyde and not acetaldehyde itself is responsible for in vivo ethanol-induced lipid peroxidation in rats.
A single oral administration of ethanol (5 g/kg) to rats induced a marked increase in lipid peroxidation, in the liver and kidney within 9 hr, as assessed by malondialdehyde accumulation. The pretreatment with alcohol dehydrogenase (ADH) inhibitor, 4-methylpyrazole (1 mmol/kg) caused approximately 50% inhibition of the hepatic ADH activity and abolished this ethanol-induced lipid peroxidation. The disulfiram treatment (100 mg/kg) significantly inhibited 63% of the hepatic low Km aldehyde dehydrogenase (ALDH) but not the high Km ALDH. The cyanamide treatment (15 mg/kg) effectively decreased 83% of the low Km and 70% of the high Km ALDH in the liver. Although there was more than a 20-fold elevation of acetaldehyde levels by the inhibition of acetaldehyde metabolism with disulfiram or cyanamide, the ethanol-induced lipid peroxidation was significantly suppressed by pretreatment with these drugs. More than 90% inhibition of xanthine oxidase and dehydrogenase by the pretreatment with allopurinol (100 mg/kg), with no effect on the hepatic ADH and ALDH activities, did not alter the enhancement of lipid peroxidation following ethanol administration. We propose that the metabolism of acetaldehyde (probably via the low Km ALDH) and not acetaldehyde itself is responsible for the ethanol-induced lipid peroxidation in vivo and that the contribution of xanthine oxidase, as an initiator of lipid peroxidation through acetaldehyde oxidation is minute during acute intoxication.
Kera
Y
Y
Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan.
Ohbora
Y
Y
Komura
S
S
D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000502:physiology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014969:Xanthine Oxidase / Q000502:physiology
D011720:Pyrazoles; D000431:Ethanol; D008315:Malondialdehyde; D000077604:Fomepizole; D014969:Xanthine Oxidase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde