Zenser T V, Davis B B
Fundam Appl Toxicol. 1984 Dec;4(6):922-9. doi: 10.1016/0272-0590(84)90230-6.
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.
研究了肾脏混合功能氧化酶和前列腺素H合酶对药物和外源性物质的代谢。在皮质和外髓质中观察到显著的混合功能氧化酶活性。然而，在内髓质中未检测到混合功能氧化酶活性。相反，前列腺素H合酶在内髓质和外髓质中相当活跃，而在皮质中未检测到活性。前列腺素H合酶通过其氢过氧化物酶活性激活多种原毒素和前致癌物。对乙酰氨基酚和联苯胺的过氧化物激活似乎涉及自由基中间体的形成，该中间体与大分子上的亲核位点结合。后者被认为会引发致病作用。前列腺素H合酶是对肾内髓质产生病理作用的化学物质混合功能氧化酶激活的一种潜在替代方式。
