Abstract

Administration of a single dose of methylmercuric chloride (MMC) to male rats results in significant decreases in hepatic ethylmorphine N-demethylase, aniline hydroxylase, cytochrome P-450 content, and an increase in hexobarbital sleeping time at 24 and 72 hr. Addition of MMC to hepatic microsomes resulted in inhibition of ethylmorphine N-demethylase activity at all concentrations of MMC tested. MMC at low concentrations enhanced aniline hydroxylase activity, whereas at high concentrations marked inhibition of the hydroxylase occurred. Addition of MMC to microsomal suspensions also resulted in a partial conversion of cytochrome P-450 to cytochrome P-420. In vitro. NADPH-cytochrome c reductase was more susceptible to MMC inhibition than was the conversion of cytochrome P450 to cytochrome P-420. The in vitro inhibition of ethylmorphine N-demethylase and aniline hydroxylase activities and the conversion of cytochrome P-450 to cytochrome P-420 could be prevented by supplementing microsomes with cytosol. These data indicate that the inhibitory effects of methylmercury on microsomal enzymes in vivo may be indirect and not solely dependent on enzyme inhibition.