Synergistic effects of phorone on the hepatotoxicity of bromobenzene and paracetamol in mice.
Administration of phorone (diisopropylidene acetone), an industrial solvent, to mice caused a rapid depletion of hepatic glutathione, which is due to enzymatic conjugation of phorone with glutathione, mediated by cytoplasmic enzymes of the liver. Whereas phorone, even in high doses, did not show hepatotoxic effects by itself, combined administration of phorone with a subtoxic dose of either paracetamol or bromobenzene strongly enhanced hepatotoxicity of the latter compounds as was judged from a rise in serum transaminase activities. These findings are compatible with the concept of a dose threshold for biologically reactive intermediate compounds which are bioinactivated through glutathione conjugation.
D000082:Acetaminophen / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001969:Bromobenzenes / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011247:Pregnancy; D012997:Solvents / Q000494:pharmacology*
D001969:Bromobenzenes; D007659:Ketones; D012997:Solvents; D000082:Acetaminophen; C018637:phorone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione