Enzyme Systems Involved in the Formation of Reactive Metabolites in the Renal Medulla;

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. Peroxidatk 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. © 1984 Society of Toxicology. One of the primary functions of the kidney is the excretion of toxic compounds. The major route of excretion is usually glomerular filtration and/or tubular secretion [for a de