Sex-related effect of cadmium on hepatic cytochrome p-450, drug-metabolizing enzymes and 5-aminolevulinic acid synthetase and heme oxygenase in the rat

Abstract

The effect of cadmium on hepatic cytochrome P-450 containing drugmetabolizing enzymes, δ-aminolevulinic acid synthetase (ALA synthetase) and heme oxygenase activity in both male and female rats was examined to define the nature of sex differences in response. In male rats injected i.p. with a single dose of cadmium chloride (1.25 mg Cd/kg body weight) there was a reciprocal relationship between the decrease of cytochrome P-450 levels and drug-metabolizing enzymes and the increase of heme oxygenase activity for up to 120 h. Hepatic ALA synthetase activity was initially decreased and returned to control levels at 24 h. In female rats, cadmium initially produced similar effects to those seen in male rats, but these were of shorter duration except for the increase of heme oxygenase activity. In addition, ALA synthetase activity was slightly increased at 24 h and 48 h. The results suggest that the sex differences in response reside mainly in the duration of the metal effect on these hepatic enzymes.