Effect of preexposure to kepone on hepatic mixed-function oxidases in the female rat

Abstract

The effects of preexposure of female rats to Kepone on hepatic drugmetabolizing enzymes and several other parameters of the multifunction oxidase system were investigated. Animals were exposed to 0, 50, 100, and 150 ppm Kepone in the daily ration for 16 days. There was a dose-related decline in body weight gained to 72, 55, and 22% of the controls for 50, 100, and 150 ppm Kepone, respectively. Liver weight was unaltered at all three levels of dietary Kepone. While hydroxylation of aniline, pentobarbital, and hexobarbital were all enhanced, the increase in metabolism of the latter two substrates was consistently higher than that of controls. Enhanced metabolism of pentobarbital was also evident from the dose-related decrease in the pentobarbital-induced sleeping time. Aminopyrine and ethylmorphine demethylase activities were increased three- to fourfold over the controls. Cytochrome P-450, NADPH-cytochrome c reductase, and aniline binding were all increased, suggesting that there were general increases in the intermediate steps in the electron-transfer system within the multifunction oxidase complex. Cytochrome b 5 was unaltered by Kepone and only a 100-ppm dose elicited a discernible increase in NADPH dehydrogenase activity. These effects in the female rats, along with previously published effects in the male rat, are suggestive of the potential of Kepone to modify hepatic drug-metabolizing function in animals of both sexes.