The effects of cadmium on microsomal drug metabolizing enzyme system in rat livers

Masaru Sagai, Fujio Shiraishi, Kentaro Kubota
1977 Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)  
Cadmium chloride administered intraperitoneally to rats caused a mainly dose-dependent decrease of microsomal protein and the cytochrome P-450 contents in the hepatic microsomal drug-metabolizing enzyme system. This dose-dependent decrease of cytochrome b5 was slight. The concentrations of cadmium that decreased the activity of this system show no effect on sGOT and sGPT activity in this experiment. Cadmium added in vitro caused the denaturation of cytochrome P-450 to cytochrome P-420, and the
more » ... ome P-420, and the denaturation was dependent on the concentration of cadmium. Experiments on the effect of cadmium on the activity of aminopyrine demethylase and aniline hydroxylase dependent cytochrome P-450 were conducted in vivo and in vitro. The specific activity of the former was decreased more remarkably than that of the latter by cadmium administered in vivo. On the other hand, in in vitro experiment, aniline hydroxylase was inhibited much more than aminopyrine demethylase. Enzyme kinetics to determine the inhibitory mechanism of aminopyrine demethylase and aniline hydroxylase were also conducted. These results may indicate that the decrease of drug-metabolizing enzyme activity is mainly due to the denaturation of cytochrome P-450 rather than the inhibition of the terminal oxidase by cadmium.
doi:10.1265/jjh.32.463 fatcat:dxbph7n3wjf4hgwlosapgr7m3e