Effect of toluidines on drug metabolizing enzymes in rat liver, kidney and lung.

The effect of pretreatment with o-, m- and p-toluidine on the drug-metabolizing enzymes of liver, kidney and lung in rats were investigated. The activities of microsomal aryl hydrocarbon hydroxylase (AHH), aminopyrine demethylase, NADPH-cytochrome c reductase, epoxide hydrolase, cytosolic glutathione S-transferase as well as the concentrations of cytochrome P-450 and cytochrome b5 were determined. The obtained results showed that o-toluidine increased the activity of AHH in all tested organs; a particularly marked increase was observed in the kidney. The activity of NADPH-cytochrome c reductase and the content of cytochrome b5 were enhanced by o-toluidine only in the liver. m-Toluidine enhanced the glutathione S-transferase activity while the p-isomer increased both the epoxide hydrolase and the glutathione S-transferase activities. p-Toluidine decreased the AHH and aminopyrine demethylase activities and the cytochrome P-450 content. These results may explain in part the previously reported observations on carcinogenic activity of o-toluidine.