Induction of rat hepatic drug metabolizing enzymes by substituted urea herbicides.
Effects of eight structurally closely related substituted urea herbicides were investigated on the induction of cytochrome P-450 dependent monooxygenase enzyme complex, as well as on two conjugating enzymes after short-term treatment of rats. Liver microsomal cytochrome P-450 content was induced approximately by 50%. Cytochrome P-450 dependent monooxygenase activities showed a great variety depending on the substrate and on the herbicide. Two-18-fold induction was detected with 7-ethoxycoumarin, while up to 8-fold induction was measured with benzo(a)pyrene. Aldrin epoxidase activities were increased up to 3-fold, and aminopyrine N-demethylase activities were only slightly different from the control level. UDP-glucuronyltransferase and glutathione S-transferase activities were enhanced up to 2-fold. The results indicate that chemical structure of the related substituted urea compounds, the number of halogen substituents on their phenyl group exert a strong influence on the induction of monooxygenases.
D015660:7-Alkoxycoumarin O-Dealkylase; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D006540:Herbicides; D010671:Phenylurea Compounds; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C019647:aldrin epoxidase; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001579:Benzopyrene Hydroxylase; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D009245:NADH Dehydrogenase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase