Species and Sex Differences in Selenium Inhibition of Hepatic Drug Metabolism in Rodents

ABSTRACT

Hepatic microsomal drug metabolism was assessed in male and female rats, mice and hamsters 72 hr after administration of sodium selenite. The greatest inhibitory effect of selenium on hepatic drug metabolism occurred in male rats where the magnitude of reduction in microsomal, metabolism by selenium treatment of ethylmorphine and aminopyrine was disproportionately greater than the decrease in either cytochrome P-450 levels or metabolism of aniline. In contrast, the inhibition of metabolism of the three substrates in female mice and the decrease in ethylmorphine-N-demethylase in male mice were similar in magnitude to the reduction observed in cytochrome P-450 content. Hepatic microsomal metabolism in male and female hamsters was relatively resistant to the inhibitory effects of selenium. The inhibition of drug metabolism by selenium may reflect a specific effect of selenium on selected isozymes of cytochrome P-450.