Increased retinoic acid metabolism following 3,3',4,4',5,5'-hexabromobiphenyl injection.
Young male Wistar rats received single i.p. injections of 3,3',4,4',5,5'-hexabromobiphenyl. In rats dosed with 40 mg/kg, food consumption and growth as well as liver retinol and retinyl palmitate concentrations decreased, while serum retinol and liver weight increased within 28 days following the injection. In rats receiving a 20-mg/kg dose, food consumption, growth, liver weight, and serum retinol were not affect, although liver retinol and retinyl palmitate concentrations declined to 23 and 21% of their respective control values. Vitamin A metabolism was studied in liver microsomes prepared from rats sacrificed 7 days after the 20-mg/kg injection. The rate of retinoic acid hydroxylation via the cytochrome P-450 system to 4-hydroxyretinoic acid plus the subsequent oxidation to 4-ketoretinoic acid was significantly elevated. Retinoic acid conjugation by UDP-glucuronyl transferase was also significantly increased. These changes corresponded with increased activities of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and UDP-glucuronyltransferase conjugation of p-nitrophenol. These results provide a direct link between enzyme induction due to xenobiotics and specific steps in the vitamin A metabolic pathway.
Spear
P A
PA
Laboratoire de physiologie de la nutrition, Université de Bordeaux I, Talence, France.
Garcin
H
H
Narbonne
J F
JF
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004224:Diterpenes; D014453:Glucuronosyltransferase / Q000378:metabolism; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000084562:Retinyl Esters; D014212:Tretinoin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism
D004224:Diterpenes; D009596:Nitrophenols; D011075:Polybrominated Biphenyls; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin; C019429:4-hydroxyretinoic acid; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; C032790:3,3',4,4',5,5'-hexabromobiphenyl; C024836:4-nitrophenol