Dose dependent activation of rat small intestinal monooxygenase-activity towards benzo(a)pyrene and 7-ethoxycoumarin after oral pretreatment with cimetidine.
Arylhydrocarbon-hydroxylase and 7-ethoxycoumarin O-deethylase were stimulated in intestinal microsomes prepared two hours after administration of cimetidine (25 mg/kg, p.o.) to male Wistar rats. Moreover, the metabolite-pattern of benzo(a)pyrene was changed as compared to that in control (saline, 2 hr) animals. Cytochrome P-450 content was not affected. However, rats receiving higher doses of cimetidine (75 and 150 mg/kg) showed a dose dependent decrease in diolformation from benzo(a)pyrene. We were not able to achieve similar effects on monooxygenase activity by in vitro pretreatment of intestinal cells and/or microsomes. Observed interaction might implicate an effect of cimetidine on carcinogenic activity in small intestine of polycyclic aromatic hydrocarbons.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism*; D002927:Cimetidine / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010105:Oxygenases / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D002273:Carcinogens; D002083:Butylated Hydroxyanisole; D001564:Benzo(a)pyrene; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases