Kepone induction of hepatic mixed function oxidases in the male rat

Abstract

Effect of preexposure to kepone on hepatic drug metabolizing enzymes and several parameters of mixed function oxidase (MFO) system was investigated. Male rats were exposed to 0, 50, 100 and 150 ppm kepone in the daily ration for 16 days. Gain in body weight was declined after kepone to 86, 62 and 33% of controls for 50, 100 and 150 ppm kepone respectively. Liver weight was unaltered at all three levels of kepone. While hydroxylation of both aniline and pentobarbital was enhanced, the increased in aliphatic hydroxylation (i.e., pentobarbital) were greater at all levels of exposure to kepone. Aminopyrine demethylase was enhanced roughly 3 fold at 50 ppm kepone and was not further increased at higher levels of kepone. Cytochrome P 450, NADPH-cytochrome c reductase, and aniline binding were all increased suggesting that there were general increases with intermediate steps of the electron transfer and drug oxidation system. Cytochrome b 5 and NADPH dehydrogenase were unaltered after kepone treatment. These results suggest that kepone is an efficient inducer of hepatic MFO system.