Induction of rat hepatic microsomal enzymes by toxaphene pretreatment.

Abstract

The effects of pretreatment of rats with toxaphene on hepatic drug metabolizing enzymes and several other parameters of the mixed function oxidase system were investigated. Adult male Sprague-Dawley rats were fed diets containing 0, 50, 100, 150 and 200 ppm of toxaphene for 14 days. The body weight gain was unaltered as well as the food consumption in all the toxaphene fed groups. There was no change in the weights of brain, kidney, heart, and testes but the liver weight was significantly increased. The thymus weight in all the toxaphene fed grups was decreased. Hydroxylation of pentobarbital and aniline was significantly enhanced in rats exposed to toxaphene. Ethylmorphine-N-demethylase activity in the toxaphene treated rats was also elevated. Enhanced hydroxylation of pentobarbital was also evident from the decreased sleeping time following pentobarbital administration. Exposure to toxaphene increased cytochrome P-450, NADPH-cytochrome c-reductase and dehydrogenase in hepatic microsomal fractions. The binding of aniline and hexobarbital to microsomes was also enhanced, suggesting that the intermediate steps in the electron-transfer system were increased. In conclusion, pretreatment of rats with toxaphene for fourteen days resulted in the induction of the hepatic mixed function oxidase system.