Hepatotoxicity of pulegone in rats: its effects on microsomal enzymes, in vivo.
Oral administration of pulegone (400 mg/kg) to rats once daily for five days caused significant decreases in the levels of liver microsomal cytochrome P-450 and heme. Cytochrome b5 and NAD(P)H-cytochrome c-reductase activities were not affected. Massive hepatotoxicity accompanied by an increase in serum glutamate pyruvate transaminase (SGPT) and a decrease in glucose-6-phosphatase were observed upon treatment with pulegone. A significant decrease in aminopyrine N-demethylase was also noticed after pulegone administration. Menthone or carvone (600 mg/kg), compounds related to pulegone, when administered orally did not cause any decrease in cytochrome P-450 levels. The hepatotoxic effects of pulegone were both dose and time dependent. Pretreatment of rats with phenobarbital (PB) or diethylmaleate (DEM) potentiated the hepatotoxicity caused by pulegone, whereas, pretreatment with 3-methylcholanthrene (3-MC) or piperonyl butoxide protected from it. It appears that a PB induced cytochrome P-450 catalysed reactive metabolite(s) may be responsible for the hepatotoxicity caused by pulegone.
Moorthy
B
B
Department of Organic Chemistry, Indian Institute of Science, Bangalore.
Madyastha
P
P
Madyastha
K M
KM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D000081005:Cyclohexane Monoterpenes; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors; D006418:Heme / Q000378:metabolism; D008107:Liver Diseases / Q000201:enzymology; D008297:Male; D008610:Menthol / Q000031:analogs & derivatives* / Q000633:toxicity; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D039821:Monoterpenes; D051381:Rats; D013997:Time Factors
D000081005:Cyclohexane Monoterpenes; D065607:Cytochrome P-450 Enzyme Inhibitors; D039821:Monoterpenes; D008610:Menthol; D006418:Heme; C039648:pulegone; D000410:Alanine Transaminase; D005952:Glucose-6-Phosphatase