Effect of manganese on hepatic drug metabolism in male and female rats.

Experiments were conducted to examine the effect of manganese on drug response and metabolism in male and female rats. Three days after administration of manganese chloride (5 mg Mn/kg, ip), the duration of hexobarbital hypnosis was prolonged in male but not in female rats. Hepatic microsomal metabolism of aniline, ethylmorphine, and hexobarbital was significantly inhibited in male rats. Metabolism of aniline and ethylmorphine was also inhibited in female rats but to a lesser extent than in males. Hexobarbital metabolism was not inhibited in female rats. Cytochrome P-450 content was depressed only in male rats, while cytochrome b5 levels were decreased in both sexes. These results indicate that sex-related differences exist in the ability of manganese to alter drug response and metabolism.