Inhibition of hepatic drug metabolizing enzyme by cadmium in mice.

Abstract

The effect of cadmium on hepatic drug metabolizing enzymes and the involvement of metallothionein in the protection of the impaired activity of these enzymes was studied. Administration of cadmium (cadmium chloride) to mice significantly inhibited the activity of aminopyrine N-demethylation in 24 and 48 hr, but the activity returned to nearly control values in 72 hr. The intensity of the inhibition of drug metabolizing enzymes was dose-dependent, suggesting that the inhibition was a result of a direct action of cadmium upon the drug metabolizing enzymes. The inhibition of hepatic drug metabolizing enzymes and the decrease in cytochrome P-450 content by the challenging dose were diminished when mice were pre-dosed with cadmium chloride. The degree of protection against the challenging dose was correlated with the pre-dose levels. The effect of the challenging dose on hepatic drug metabolizing enzymes and cytochrome P-450 content was completely abolished when mice were pre-dosed with 3 mg/kg dose level of cadmium chloride. It is considered that metallothionein may be involved in the biological protection of animals against cadmium poisoning. (ND)