Renal cortical drug and xenobiotic metabolism following urinary tract obstruction

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. Metabolisme cortical renal des medicaments et xenobiotiques apres obstruction du tractus urinaire. Le metabolisme cortical renal de medicaments et de xenobiotiques a ete etudie avec des microsomes prepares a partir des reins normaux, controlaterals, et hydronephrotiques, 4 jours apres une obstruction. Les systemes microsomiaux de fonction oxydase mixte et de prostaglandine H synthetase ont ete determines chez des lapins controles et traites par du 3-methylcholanthrene. Le contenu en cytochrome P450 et l'activite biphenyl-4-hydroxylase, mais non l'activite cytochrome c reductase etaient diminues dans le rein hydronephrotique. Le traitement par le 3-methylcholanthrene a augmente le contenu en cytochrome P450 et les activites biphenyl-4-hydroxylase et acetanilide-4-hydroxylase chez les reins normaux, controlaterals et hydronephrotiques. Cependant, meme apres traitement par le 3-methylcholanthrene, le contenu en cytochrome P450 du rein hydronephrotique et son activite acetanilide-4-hydroxylase n'etaient pas de plus de 20% des valeurs dans le rein normaux correspondant. Le metabolisme de la benzidine par la prostaglandine H synthetase etait observable dans le rein hydronephrotique, mais etait a la limite de la detection dans les reins normaux ou controlaterals, avec ou sans traitement par le 3-methylcholanthrene. Les caracteristiques du metabolisme de la benzidine etaient plus compatibles avec l'activite hydroperoxidase qu'avec l'activite cyclooxygenase des acides gras de la prostaglandine H synthetase. Ainsi, l'hydronephrose altere le profil metabolique des drogues et des xenobiotiques dans le cortex renal d'un systeme primitivement dependant d'une fonction oxydase mixte a un systeme ayant la capacite de metabolisme par le constituant hydroperoxydase de la prostaglandine H synthetase.