Cadmium alteration of hexobarbital action: Sex-related differences in the rat

Three days after ip administration of a single cadmium dose (0.84 mg of Cd/kg), duration of hexobarbital hypnosis was significantly potentiated in male but not in female rats. Cadmium in larger doses of 2, 4, and 6 mg/kg, ip, did not alter duration of hexobarbital hypnosis in female rats, although lethality was observed 24 hr after administration of the two higher cadmium doses. Hepatic microsomal metabolism of hexobarbital was significantly decreased in male rats but not in females when measured 72 hr after cadmium administration (2 mg/kg, ip). Addition of cadmium in concentrations ranging from 5 × 10^?6m to 5 × 10^?3m to microsomes isolated from untreated male and female rats produced a dose-dependent inhibition of hexobarbital metabolism at all Cd concentrations in males. In female-derived microsomes a significant inhibition of hexobarbital metabolism was observed only at higher cadmium concentrations (5 × 10^?4m and 5 × 10^?3m). These data suggest that a sex-related difference exists in the ability of cadmium to alter response to hexobarbital in the rat which appears to be mediated through differences in hepatic microsomal metabolism.