Neonatal exposure to cadmium alters the responses of the hepatic monooxygenases to phenobarbital and to cadmium in adult male rats.
The effects of a single dose of Cd (1.27 mg/kg), within 6 hr of birth, on the hepatic monooxygenase system of the immature and the adult rat were investigated. Cd, administered neonatally, affected neither the basal enzymatic activities nor the levels of the electron transport components in either 8- or 60-day-old rats. However, it increased the loss of cytochrome P450 (by 28%) and elevated the inhibition of both ethylmorphine demethylase (by 28%) and aniline hydroxylase (by 32%) beyond that caused by Cd (1.27 mg/kg) administered to the 60-day-old adult. The greater inhibition of the demethylase and the hydroxylase in the rats (pre-)treated at birth was abolished when the activities were expressed per nanomole of cytochrome P450. This suggests that the increased sensitivity of Cd resides in the cytochrome P450. The decrease in the activity of NADPH cytochrome c reductase caused by treating 60-day-old rats with Cd was not affected by a previous exposure to Cd in the neonatal period. Similarly, compared to normal controls, Cd given neonatally did not alter the induction of aniline hydroxylase by phenobarbital (50 mg/kg/day/4 days) in the 60-day-old rat. However, the induction responses of cytochrome P450 and the reductase were attenuated 19 and 14% while those of ethylmorphine demethylase and hexobarbital hydroxylase were decreased by 28 and 17%. The activities of the latter two enzymes did not differ between control and cadmium groups when expressed either in terms of cytochrome P450 or NADPH cytochrome c reductase. This suggests that neonatally administered Cd depresses their induction through the cytochrome and/or the reductase.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002104:Cadmium / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis*; D010179:Pancreas / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D002104:Cadmium; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010634:Phenobarbital