Inhibition of acetaminophen activation by ethanol and acetaldehyde in liver microsomes.
Mechanisms of the inhibitory effect of ethanol on acetaminophen hepatotoxicity are controversial. We studied the effects of ethanol and acetaldehyde, an oxidative metabolite of ethanol, on NADPH-dependent acetaminophen-glutathione conjugate production in liver microsomes. Ethanol at concentrations as low as 2mM prevented the conjugate production noncompetitively. Acetaldehyde also inhibited acetaminophen-glutathione conjugate production at concentrations as low as 0.1mM that is comparable with those observed in vivo after social drinking. Acetaldehyde may be involved in ethanol-induced inhibition of acetaminophen hepatotoxicity.
Sato
C
C
Division of Health Science, School of Allied Health Sciences, Tokyo Medical and Dental University, Japan.
Liu
J
J
Miyakawa
H
H
Nouchi
T
T
Tanaka
Y
Y
Uchihara
M
M
Marumo
F
F
D000079:Acetaldehyde / Q000494:pharmacology*; D000082:Acetaminophen / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000082:Acetaminophen; D000431:Ethanol; D000079:Acetaldehyde