Effect of fatty acids on formation, distribution, storage, and release of benzo(a)pyrene phenols and glucuronides in the isolated perfused rat liver.
The hydroxylation of benzo(a)pyrene and conjugation, storage, and release of benzo(a)pyrene phenols and glucuronides by the perfused rat liver were studied in the presence and absence of acute addition of physiological concentrations of common dietary fatty acids. The actions of fatty acids on the oxidation and conjugation of benzo(a)pyrene in the intact liver were compared with their actions on microsomes isolated from rat liver. Rats were treated with beta-naphthoflavone to stimulate polycyclic aromatic hydrocarbon metabolism. Long-chain fatty acyl CoA compounds (palmitoyl CoA, oleoyl CoA, linolenoyl CoA; 50 microM) inhibited hydroxylation of benzo(a)pyrene by isolated microsomes by about 45%; however, long-chain fatty acids did not affect overall rates of hydroxylation of benzo(a)pyrene by the perfused liver at concentrations ranging up to 300 microM. The medium-chain acyl CoA compound, octanoyl CoA, also did not affect benzo(a)pyrene hydroxylation in microsomes or liver. Although fatty acids did not alter rates of hydroxylation, the ratio of free benzo(a)pyrene phenols to glucuronides (F/G ratio) increased about 60% (P less than 0.05) in livers perfused with long-chain fatty acids (palmitate, oleate, linolenate). Inhibition of glucuronidation was not observed with the medium-chain fatty acid, octanoate. Benzo(a)pyrene phenols and glucuronides accumulated linearly in the liver at rates of approximately 40 nmol/g/h. A second action of both long- and medium-chain length fatty acids was to increase rates of release of benzopyrene phenols into the perfusate by 50 to 80%. Fatty acids did not effect release of benzo(a)pyrene phenols and glucuronides into bile. Taken together, these data support the hypothesis that fatty acids displace carcinogenic metabolites of benzo(a)pyrene from binding sites in the liver which enter the circulation and travel to target tissues.
Zhong
Z
Z
Department of Pharmacology, University of North Carolina, Chapel Hill 27514.
Gao
W
W
Kauffman
F C
FC
Thurman
R G
RG
D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001646:Bile / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010636:Phenols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D005965:Glucuronates; D009829:Oleic Acids; D010636:Phenols; D019301:Oleic Acid; D001564:Benzo(a)pyrene