Abstract
INOMATA, N., YOSHIDA, H., AOKI, Y., TSUNODA, M. and YAMAMOTO, M. Effects of MCPA and Other Phenoxyacid Compounds on Hepatic Xenobiotic Metabolism in Rats. Tohoku J. Exp. Med., 1991, 165 (3), 171-182-The effects of ethyl 4-chloro-2-methylphenoxyacetate (MCPA) and other phenoxyacid compounds on hepatic xenobiotic metabolizing enzymes were studied in male rats. These compounds were administered orally 200mg/kg/day to the rats for 2 weeks. Both MCPA and clofibrate increased the hepatic level of cytochrome P-450. In the MCPA-treated group, the activities of aniline hydroxylase and 7-ethoxycoumarin O-deethylase increased by 15% and 1.5-fold, respectively. The free acid form of MCPA increased these activities more potently than MCPA. Both MCPA and its free acid did not change the activity of aminopyrine N-demethylase. A marked increase in the activity of aniline hydroxylase was noted in the 2, 4-dichlorophenoxyacetic acid-treated group, whereas the aminopyrine N-demethylase activity significantly decreased in the same group. Clofibrate also increased the activities of hepatic microsomal cytochrome P-450-mediated oxidation tested, but to a lesser extent when compared with the effects of MCPA. These results indicate that MCPA may have a potent effect on the hepatic metabolizing enzymes in rats, and also that the induction of xenobiotic metabolizing enzymes may change when the chemical moiety of phenoxyacid compounds is modified.
