Laboratory Investigation

Kidney International (1984) 25, 747–752; doi:10.1038/ki.1984.85

Renal cortical drug and xenobiotic metabolism following urinary tract obstruction

Terry V Zenser, Neville S Rapp, Michael B Mattammal and Bernard B Davis

The Geriatric Research, Education and Clinical Center, St. Louis Veterans Administration Medical Center, and Departments of Biochemistry and Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri

Correspondence: Dr T Zenser, Geriatric Center (111G JB), Veterans Administration Medical Center, St. Louis, Missouri 63125, USA

Received 18 March 1983; Revised 5 October 1983.

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Abstract

Renal cortical drug and xenobiotic metabolism following urinary tract obstruction. Renal cortical metabolism of drugs and xenobiotics was assessed with microsomes prepared from normal, contralateral and 4-day postobstructive hydronephrotic kidneys. Microsomal mixed-function oxidase and prostaglandin H synthase systems were determined in control and 3-methylcholanthrene-treated rabbits. Cytochrome P450 content and biphenyl-4-hydroxylase activity but not cytochrome c reductase activity were reduced in the hydronephrotic kidney. 3-Methylcholanthrene treatment increased cytochrome P450 content and biphenyl-4-hydroxylase and acetanilide-4-hydroxylase activities in normal, contralateral, and hydronephrotic kidneys. However, even after 3-methylcholanthrene treatment, hydronephrotic kidney cytochrome P450 content and acetanilide-4-hydroxylase activity were not more than 20% of the corresponding normal kidney values. Prostaglandin H synthase metabolism of benzidine was observed in the hydronephrotic kidney but was at the limit of detection in normal or contralateral kidneys with or without 3-methylcholanthrene treatment. Characteristics of benzidine metabolism were consistent with the hydroperoxidase rather than the fatty acid cyclooxygenase activity of prostaglandin H synthase. Therefore, hydronephrosis alters the drug and xenobiotic metabolic profile of the renal cortex from a primarily mixed-function oxidase-dependent system to one with the potential for metabolism by the hydroperoxidase component of prostaglandin H synthase.

Métabolisme cortical rénal des médicaments et xénobiotiques après obstruction du tractus urinaire. Le métabolisme cortical rénal de médicaments et de xénobiotiques a été étudié avec des microsomes préparés à partir des reins normaux, controlatérals, et hydronéphrotiques, 4 jours après une obstruction. Les systèmes microsomiaux de fonction oxydase mixte et de prostaglandine H synthétase ont été déterminés chez des lapins contrôles et traités par du 3-méthylcholanthrène. Le contenu en cytochrome P450 et l'activité biphényl-4-hydroxylase, mais non l'activité cytochrome c réductase étaient diminués dans le rein hydronéphrotique. Le traitement par le 3-méthylcholanthrène a augmenté le contenu en cytochrome P450 et les activités biphényl-4-hydroxylase et acétanilide-4-hydroxylase chez les reins normaux, controlatérals et hydronéphrotiques. Cependant, même après traitement par le 3-méthylcholanthrène, le contenu en cytochrome P450 du rein hydronéphrotique et son activité acétanilide-4-hydroxylase n'étaient pas de plus de 20% des valeurs dans le rein normaux correspondant. Le métabolisme de la benzidine par la prostaglandine H synthétase était observable dans le rein hydronéphrotique, mais était à la limite de la détection dans les reins normaux ou controlatérals, avec ou sans traitement par le 3-méthylcholanthrène. Les caractéristiques du métabolisme de la benzidine étaient plus compatibles avec l'activité hydroperoxidase qu'avec l'activité cyclooxygénase des acides gras de la prostaglandine H synthétase. Ainsi, l'hydronéphrose altère le profil métabolique des drogues et des xénobiotiques dans le cortex rénal d'un système primitivement dépendant d'une fonction oxydase mixte à un système ayant la capacité de métabolisme par le constituant hydroperoxydase de la prostaglandine H synthétase.

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