Induction of hepatic microsomal drug metabolizing enzyme system by levamisole in male mice.
To examine the effect of levamisole on the hepatic drug metabolizing enzyme system of mice, levamisole at a dose of 20 mg kg-1 day-1 was administered i.p. for 5 days. Compared with the control values, the levamisole treatment significantly increased the amount of cytochrome P450 and cytochrome b5 and the in-vitro activities of aminopyrine N-demethylase, benzphetamine N-demethylase and aniline hydroxylase. In contrast, there was no change in microsomal NADPH-cytochrome c reductase activity in-vitro or in the relative liver weight and microsomal protein content compared with the corresponding values for control mice. Furthermore, in-vivo induction of drug metabolism was demonstrated by decreased pentobarbitone sleeping times after levamisole pretreatment. These results indicate that certain hepatic microsomal mixed function oxidases of mice are induced by levamisole, the drug that is frequently used as an anthelmintic in veterinary medicine and as an immunostimulant drug in human medicine.
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Department of Physiology and Pharmacology, School of Veterinary Medicine, Tuskegee University, Alabama 36088.
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D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D015786:Cytochromes b5 / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D007978:Levamisole / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D014176:Protein Biosynthesis; D012890:Sleep / Q000187:drug effects
D007978:Levamisole; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D010424:Pentobarbital