Effects of phenobarbital on aniline metabolism in primary liver cell culture of rats with ethionine-induced liver disorder.
In experiment 1, the amount of aniline (AN) metabolites in the primary cell culture medium of the liver cells obtained from ethionine (ET)-treated rats was compared with that of the control (normal) rats. Although the metabolites detected in both groups were p-aminophenol (p-AP), N-acetyl-p-AP (AAP), acetoanilide (AAN), AAP-glucuronide (AAPG), phenylhydroxylamine sulfate (PHAS) and p-AP-glucuronide (p-APG), the amount of AAP was lower and that of p-APG was markedly higher in the ET-treated rats than in the control rats. In experiment 2, phenobarbital (PB) was orally administered to the ET-treated and control rats at a dose of 100 mg/kg. The time course changes in AN metabolites in the primary cell culture medium of liver cells obtained at 2 or 48 hr after PB treatment were compared with those without PB treatment. In the ET-treated rats, the amount of PHAS was slightly higher at 2 hr after PB treatment, and that of AAP was lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. In the control rats, the amounts of AAP, AAN, p-AP and p-APG at 2 hr after PB treatment remained lower than those without PB treatment, and that of AAP was markedly lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. These findings indicated greater detoxication in the primary liver cell culture in the ET-treated rats than in the control rats. Furthermore, detoxication was greater in the primary cell culture of liver cell obtained from the ET-treated rats after PB treatment than from those without PB treatment, because the production of acetylates (AAP) decreased and p-APG increased (induction of conjugated enzyme) in the PB treatment group.
Noguchi
M
M
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Nitoh
S
S
Mabuchi
M
M
Kawai
Y
Y
D000082:Acetaminophen / Q000378:metabolism; D000627:Aminophenols / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D005001:Ethionine; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000627:Aminophenols; D000814:Aniline Compounds; D003470:Culture Media; C027988:2-aminophenylglucuronide; D000082:Acetaminophen; C023650:aniline; D005001:Ethionine; D010634:Phenobarbital