Effects of phenobarbital on drug metabolizing enzyme activities and other biochemical parameters in rats with DL-ethionine-induced liver injury.
Phenobarbital (PB) was orally administered once at a dose of 100 mg/kg to the liver injury model rats treated with DL-ethionine (ET), and the effects of PB on the liver drug metabolizing enzymes (DME) were chiefly examined. Liver weight, liver microsomal protein content, liver aniline 4-hydroxylase (ANH) activity, and aminopyrine N-dimethylase (AMD) activity were markedly increased in the ET-treated rats receiving PB. These findings suggested the induction of DME in the liver. However, the induction pattern of each enzyme was different. AMD activity at 48 hr after dosing of PB in the ET-treated rats was increased in the same degree as that in the control (normal). Whereas, ANH activity at 48 hr after dosing in the ET-treated rats was higher than that in normal rats. Liver lactate dehydrogenase (LDH) activity at 48 hr after dosing in the ET-treated rats was markedly increased, but such induction was not seen in normal rats. These findings indicates that DME in the liver is induced by PB treatment in the ET-treated rats as well as in normal rats, and that the ET-treated rats have a function of physiological adaptation similar to that in normal rats. The induction pattern of liver or serum enzymes in the ET-treated rats receiving PB was different from that in normal rats. Furthermore, the induction pattern of these enzymes in the ET-treated rats receiving PB was different from that in the normal rats, which may be attributed to the difference of localization in liver cells of these enzymes affected by PB.
Noguchi
M
M
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Fujitsuka
T
T
Honda
K
K
Kawai
Y
Y
D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004790:Enzyme Induction; D005001:Ethionine; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007770:L-Lactate Dehydrogenase; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D005001:Ethionine; D010634:Phenobarbital