Induction of Rabbit Renal Mixed-Function Oxidases by Phenobarbital: Cell Specific Ultrastructural Changes in the Proximal Tubule

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Abstract
Administration of phenobarbital (60 mg/kg) daily for 4 days to male rabbits resulted in induction of renal cytochrome P-450 (3.5-fold) and a corresponding increase in ethoxycoumarin-O-deethylase and benzphetamine-N-demethylase activity (17- and 4-fold, respectively). Kidney weight to body weight ratio and renal ethoxyresorufin-O-deethylase were not affected by phenobarbital pretreatment. Numerous focal areas of proliferation of smooth endoplasmic reticulum (SER) were evident in proximal tubule cells from phenobarbital-treated rabbits while proximal tubular cells from control rabbits had only small and sparsely located aggregates of SER. Phenobarbital-induced SER proliferation was specifically localized to the S3 segment of the proximal tubule. Proliferation was not observed in S2 cells of the proximal tubule, cells of Henle''s loop, distal tubules or collecting tubules in rabbits pretreated with phenobarbital. The biochemical heterogeneity of cell types within the proximal tubules of rabbits was demonstrated. Induction of mixed-function oxidases specifically in S3 cells of the proximal tubule may be of toxicological significance in the metabolic activation of certain nephrotoxicants.