© 1984 Oxford University Press
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Enzyme Systems Involved in the Formation of Reactive Metabolites in the Renal Medulla: Cooxidation via Prostaglandin H Synthase1
Geriatric Research, Education and Clinical Center, VA Medical Center, and Departments of Medicine and Biochemistry, St. Louis University St. Louis, Missouri 63125
Enzyme Systems Involved in the Formation of Reactive Metabolites in the Renal Medulla; Cooxidation via Prostaglandin H Synthase. ZENSER, T. V., AND DAVIS, B. B. (1984). Fundam. Appl. Toxicol. 4, 922–929. 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 nudeophilic 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.