Effects of MCPA and other phenoxyacid compounds on hepatic xenobiotic metabolism in rats.
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 200 mg/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.
Inomata
N
N
Toxicology Section, Hokuriku Seiyaku Co., Ltd., Fukui.
Yoshida
H
H
Aoki
Y
Y
Tsunoda
M
M
Yamamoto
M
M
D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D002994:Clofibrate / Q000633:toxicity; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010642:Phenoxyacetates / Q000737:chemistry / Q000633:toxicity; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000378:metabolism*
D010642:Phenoxyacetates; D011506:Proteins; D015262:Xenobiotics; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D002994:Clofibrate