Effect of chronic exposure to cadmium on hepatic drug metabolism.
: In an attempt to examine the chronic effect of low levels of cadmium on hepatic drug-metabolizing enzyme system, an experiment was carried out in which growing male rats were given 0, 5, 10, and 20 ppm of cadmium in drinking water for a period of 8 weeks. An ip administration of a hypnotic dose of pentobarbital to the cadmium-treated and the control rats 24 hr following the termination of the experiment exhibited that there was no significant difference in the drug metabolism in control and any of the treated groups. Next, liver microsomes were isolated from animals in all groups to study their ability to metabolize drugs in vitro. The results indicated that the activity of benzphetamine N-demethylase and aniline hydroxylase, and the concentration of microsomal cytochrome P-450 were almost identical in the control and treated groups. On the other hand, a single ip dose of cadmium (2 mg/kg) caused significant decrease in the vivo and in vitro microsomal drug metabolism. These results suggest that although a single ip dose of cadmium (2 mg/kg) causes significant inhibition of drug metabolism, chronic exposure to cadmium up to 20 ppm in drinking water over a period of 8 weeks is unlikely to affect hepatic drug metabolism.