Enzyme systems involved in the formation of reactive metabolites in the renal medulla: cooxidation via prostaglandin H synthase.
Metabolism of drugs and xenobiotics by renal mixed-function oxidases and prostaglandin H synthase was examined. Significant mixed-function oxidase activity was observed in the cortex and outer medulla. However, mixed-function oxidase activity was not detected in the inner medulla. In contrast, prostaglandin H synthase is quite active in the inner and outer medulla with no detectable activity in the cortex. Prostaglandin H synthase was shown to activate a variety of protoxins and procarcinogens by way of its hydroperoxidase activity. Peroxidatic activation of acetaminophen and benzidine appears to involve the formation of a free radical intermediate which binds nucleophilic sites on macromolecules. The latter is proposed to initiate pathogenic effects. Prostaglandin H synthase is a potential alternative to mixed-function oxidase activation of chemicals which exert pathologic effects on the renal inner medulla.
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D001560:Benzidines / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced; D007679:Kidney Medulla / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011463:Prostaglandins H / Q000378:metabolism*; D011817:Rabbits; D014118:Toxins, Biological / Q000633:toxicity
D001560:Benzidines; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D014118:Toxins, Biological; C029876:benzidine; D000082:Acetaminophen; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases