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.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects*; D004851:Epoxide Hydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014052:Toluidines / Q000494:pharmacology*
D014052:Toluidines; C029369:3-toluidine; D003577:Cytochrome P-450 Enzyme System; C023622:2-toluidine; D001189:Aryl Hydrocarbon Hydroxylases; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C029370:4-toluidine