Protective action of 2(3)-tert-butyl-4-hydroxyanisole (BHA) on acetaminophen-induced liver necrosis in male A/J mice.
Groups of male A/J mice were given either a regular diet or a regular diet supplemented with 1% BHA. After 10 days of feeding acetaminophen was administered intraperitoneally in amounts known to induce liver necrosis (500 mg/kg). Liver slices from the central lobe, were examined histologically for the extent of necrosis. Eight of the 17 mice treated with BHA showed no necrosis. In contrast 12 of 16 specimens from the mice treated with acetaminophen alone showed a severe centrilobular necrosis. The microsomal-mediated covalent binding of acetaminophen metabolites in-vitro was lower for microsomes from BHA pretreated mice than those from control mice. These results suggest that the ability of BHA to modify the activity of the drug metabolizing enzymes or to act as a scavenger may account for its protective action against acetaminophen-induced liver necrosis.
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D000840:Anisoles / Q000627:therapeutic use*; D002083:Butylated Hydroxyanisole / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009336:Necrosis; D011485:Protein Binding
D000840:Anisoles; D002083:Butylated Hydroxyanisole; D000082:Acetaminophen; D009249:NADP; D003577:Cytochrome P-450 Enzyme System