Effect of lentinan on the hepatic drug-metabolizing enzymes (IV) : The action of lentinan on the cytochrome P-448 dependent drug-metabolizing activities.

Abstract

Effect of lentinan on the hepatic drug-metabolizing system was studied in ddY mice (unless otherwise stated). On the assay in vivo, lentinan (1 mg/kg, i.p.) decreased cytochrome P-4 5 0 content and the activities of aminopyrine N-demethylase, aniline hydroxylase, 7-ethoxycoumarine O-deethylase and biphenyl 2- or 4-hydroxylase in the hepatic 9,000 x g supernatant or microsomes. Decreases in the activities of aminopyrine N-demethylase, aniline hydroxylase and biphenyl 2-hydroxylase were not observed in vitro. On the other hand, the effect of lentinan was weak on the hepatic drug-metabolizing enzymes in C57BL/10, C3H/He and DBA/2 mice which are nonsensitive to lentinan or do not respond to aryl hydrocarbon hydroxylase. Furthermore, the depression by lentinan on the cytochrome P-448-dependent drug-metabolizing enzymes induced by 3-methyl-cholanthrene was more greater than that on the cytochrome P-450-dependent drug-metabolizing enzymes induced by phenobarbital. This result suggests that the depression by lentinan on the hepatic drug-metabolizing system was more specific to the cytochrome P-448 induced by 3-methylcholanthrene.