title: Effect of aspirin on metabolism of acetaminophen and benzidine by renal inner medulla prostaglandin hydroperoxidase.
abstract: The effect of in vivo and in vitro aspirin treatment on renal inner medullary prostaglandin hydroperoxidase-catalyzed metabolism of acetaminophen and benzidine was examined. Metabolism was assessed by the binding of [3H]acetaminophen and [14C]benzidine to TCA-precipitable material. Microsomes were prepared from control or aspirin-treated rabbits. Aspirin, whether administered in vivo (15 mg/kg i.v.) or added in vitro (2 mM), had no effect on peroxide-initiated metabolism. By contrast, arachidonic acid-initiated metabolism was completely prevented by both in vivo and in vitro aspirin. Salicylate did not inhibit either arachidonic acid- or peroxide-dependent metabolism. The antioxidant glutathione (1 mM) completely inhibited both peroxide- and arachidonic acid-initiated metabolism. Aspirin treatment completely inhibited metabolism of arachidonic acid by medullary microsomes. Thus aspirin does not inhibit the hydroperoxidase component of prostaglandin endoperoxide synthetase, and co-oxidation of acetaminophen and benzidine may proceed in the presence of aspirin. Co-oxidation may be involved in the genesis of the nephrotoxicity of mixed analgesic abuse.
mesh_terms: D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001560:Benzidines / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D011817:Rabbits
chemical_list: D001560:Benzidines; D000082:Acetaminophen; C022464:prostaglandin hydroperoxidase; D010544:Peroxidases; D001241:Aspirin