Effects of Phenoxyherbicides and Glyphosate on the Hepatic and Intestinal Biotransformation Activities in the Rat

Abstract

The effects of phenoxyacid herbicides 2,4-D and MCPA (4-chloro-2-methylphenoxyacetic acid), clofibrate and glyphosate on hepatic and intestinal drug metabolizing enzyme activities were studied in rats intragastrically exposed for 2 wk. The hepatic ethoxycoumarin O-deethylase activity increased about 2-fold with MCPA. Both 2,4-D and MCPA increased the hepatic epoxide hydrolase activity and decreased the hepatic glutathione S-transferase activity. MCPA increased the intestinal activities of ethoxycoumarin O-deethylase and epoxide hydrolase. Glyphosate decreased the hepatic level of cytochrome P-450 and monooxygenase activities and the intestinal activity of aryl hydrocarbon hydroxylase. Clofibrate decreased the hepatic activities of UDP-glucuronosyltransferase with p-nitrophenol or methylumbelliferone as the substrate. 2,4-D decreased the hepatic activity of UDP-glucuronosyltransferase with p-nitrophenol as the substrate. MCPA decreased the intestinal activities of UDP-glucuronosyltransferase with either p-nitrophenol or methylumbelliferone as the substrate. Phenoxyacetic acids, especially MCPA, may have potent effects on the metabolism of xenobiotics. Glyphosate, not chemically related to phenoxyacids, seems to inhibit monooxygenases. Whether these changes are related to the toxicity of these xenobiotics remains to be clarified in further experiments.