Cadmium inhibition of hepatic drug metabolism in the rat

Pretreatment of rats and mice of either sex with a single 2.0 mg/kg dose of cadmium acetate (840 μg Cd ion) potentiates the action of subsequently administered hexobarbital. Three days after cadmium administration to the male rat the duration of response to hexobarbital, but not that to barbital was significantly prolonged. Plasma concentrations of hexobarbital at awakening were not different from controls, indicating that cadmium treatment had not altered central nervous system sensitivity to the barbiturate. Such treatment of male rats 3 days prior to sacrifice leads to a significant inhibition of the metabolism of aminopyrine, hexobarbital, p-nitroanisole and zoxazolamine in microsomal subfractions obtained from these animals; microsomal cytochrome P-450 is reduced to 50% of control values by the cadmium treatment. Inhibition of the metabolism of these substrates by cadmium was also achieved when the metal was added to isolated microsomes in concentrations ranging from 5 × 10^?4 to 5 × 10^?7m.