Role of quinone reductase in in vivo ethanol metabolism and toxicity.
Quinone reductase (QR), in the presence of suitable substrate, results in the regeneration of NAD+ from NADH. To test the hypothesis that QR can play a role in ethanol metabolism and toxicity, we studied the effect of a quinone as well as of induced levels of QR on ethanol administered in vivo to male rats and mice. Butylated hydroxyanisole (BHA) is known both to induce QR and to be metabolized to tert-butyl quinone (TBQ). Dietary BHA (0.75% for 10 days), followed by oral ethanol (4 g/kg, by gavage), increased the rate of ethanol disappearance and decreased the area under the curve (AUC) for blood ethanol in both rats and mice. In addition, BHA pretreatment of rats was shown to prevent ethanol-induced 24-hr hepatic triglyceride accumulation. Also, in rats, TBQ (5 mg/kg, ip) led to decreased AUC and hepatic triglyceride accumulation, although the ethanol disappearance rate was not significantly affected. TBQ in BHA-fed rats resulted in even greater effects on the ethanol disappearance rate and AUC than TBQ or BHA treatment alone. None of these treatment regimens resulted in a significant change in volume of distribution of ethanol. Thus, these results support the hypothesis that induction of QR and/or administration of quinones lead to enhanced in vivo metabolism of ethanol and decreased hepatotoxicity.
Chung
J H
JH
Division of Toxicological Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Cha
Y N
YN
Rubin
R J
RJ
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016227:Benzoquinones; D002083:Butylated Hydroxyanisole; D000431:Ethanol; D016660:NAD(P)H Dehydrogenase (Quinone); C051290:2-tert-butyl-4-quinone