Inhibition of acetaminophen hepatotoxicity by acetaldehyde in the rat.
Since we have observed that acetaldehyde, an oxidative metabolite of ethanol, inhibits acetaminophen activation in rat liver microsomes, the in vivo effect of acetaldehyde on acetaminophen hepatotoxicity was tested. In vivo experiments in 3-methylcholanthrene-pretreated male Sprague-Dawley rats showed that administration of cyanamide (20 mg/kg, i.p.) and acetaldehyde (600 mg/kg, s.c.) given 3 and 1 h, respectively, prior to acetaminophen (500 mg/kg, i.p.) but not cyanamide alone prevented acetaminophen hepatotoxicity as assessed by serum transaminases and histology. Acetaldehyde may partly be responsible for the inhibitory effect of ethanol on acetaminophen hepatotoxicity.
Liu
J
J
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Sato
C
C
Miyakawa
H
H
Kamiyama
T
T
Tajiri
K
K
Goto
M
M
Marumo
F
F
D000079:Acetaldehyde / Q000494:pharmacology*; D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000082:Acetaminophen; D003484:Cyanamide; D000079:Acetaldehyde