Acute effect of cadmium on hepatic drug-metabolizing enzymes in the rat

Abstract

Single ip injections of cadmium chloride at doses of 2.5 or 3.75 mg/kg (equivalent to 1.5 or 2.3 mg of Cd, respectively) into male Wistar rats of mean body weight of 226 ± 17 g produced significant inhibition (25–60%) of aniline hydroxylase and nitroreductase activity and also lowered the microsomal cytochrome P-450 content to 50% of the control value. These effects are in contrasto those on O-demethylase activity, which was not inhibited by either dose of cadmium chloride when enzyme activities were subsequently measured in a 0.05 m phosphate-buffered incubation system. However, the opposite conclusion was reached for the effect of these same doses of cadmium chloride when O-demethylase activity was assessed in comparable Tris-buffered systems. There appears to be a definite “buffer effect” in operation here. While the higher dose of this toxic metal salt significantly reduced the activities of the phenobarbital-induced hepatic microsomal drug-metabolizing enzymes and of cytochrome P-450, the lower dose was without significant effect on this induction, with the one exception of aniline hydroxylase when assessed in a Tris-buffer system.