BHA (2(3)-tert-butyl-4-hydroxyanisole)-mediated modulation of acetaminophen phase II metabolism in vivo in Fisher 344 rats.
Adult male Fisher 344 rats (190-220 g), were given an intravenous dose (10 mg/rat) of BHA. Pretreated and control rats received an intravenous dose of [G-3H] acetaminophen (25 mg/rat). Bile was collected prior to dosing and for 5-6 hours after dosing at varying time intervals. Separate aliquots of 0.2 ml were incubated with beta-glucuronidase and sulfatase, respectively. These incubation mixtures were then extracted and analyzed by reverse phase HPLC. In all cases control animals showed a greater deceleration in the biliary excretion of the water soluble metabolites when compared with pretreated animals. Increases in both glucuronide and sulfate elimination processes are assumed to be contributory, in part, to the overall effect of BHA on acetaminophen metabolism.
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility
D002083:Butylated Hydroxyanisole; D000082:Acetaminophen; C037386:acetaminophen glucuronide