The hepatic metabolism and biliary excretion of benzo[a]pyrene in guinea-pigs fed normal, high-fat or high-cholesterol diets.
Approx. one-third of an i.v. dose of 14C-benzo[a]pyrene was excreted within four hours in the bile of guinea-pigs fed a normal diet. The extent of excretion was not altered by feeding high-fat or high-cholesterol diets. Hepatic cytochromes P-450 and b5, and benzo[a]pyrene hydroxylase activity were unaltered by the administration of high-fat and high-cholesterol diets. Pretreatment with low oral doses of benzo[a]pyrene (6 X 3 mg/kg) did not induce these parameters in animals given any of the diets. High-fat and high-cholesterol diets altered the pattern of benzo[a]pyrene metabolites in the bile, with significantly increased excretion of dihydrodiol glucuronides in both the high-fat and high-cholesterol groups. Hepatic epoxide hydrolase activity and glutathione content were unaltered by the high-fat or high-cholesterol diets, and therefore cannot explain the alteration in the profile of biliary metabolites of benzo[a]pyrene. The altered pattern of biliary excretion in animals fed high-fat or high-cholesterol diets would lead to an increase in the delivery to the colon of dihydrodiol metabolites of benzo[a]pyrene.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004041:Dietary Fats / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism
D002791:Cholesterol, Dietary; D003573:Cytochrome b Group; D004041:Dietary Fats; D011506:Proteins; D001564:Benzo(a)pyrene; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D004851:Epoxide Hydrolases; D005978:Glutathione