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© 1983 Oxford University Press

research-article

Selective Induction and Inhibition of Renal Mixed Function Oxidases in the Rat and Rabbit

G.F. RUSH, D.M. WILSON and J.B. HOOK

Department of Pharmacology and Toxicology, Center for Environmental Toxicology, Michigan State University East Lansing, MI 48824

Selective Induction and Inhibition of Renal Mixed Function Oxidases in the Rat and Rabbit. Rush, G.F., Wilson, D.M. and Hook, J.B. (1983). Fundam. Appl. Toxicol.. 3:161-168. Renal mixed function oxidases vary in response to inducers depending on the species. Pretreatment of rabbits with ß-naphthoflavone(100 mg/kg x 4days) or pheno-barbital (60 mg/kg x 4 days) resulted in a highly selective induction of renal microsomal ethoxyresorufin-O-deethylase and benzphetamine-N-demethylase, respectively. Pretreatment of rats with ß-naphthoflavone (100 mg/kg) induced renal microsomal ethoxyresorufin and ethoxycoumarin-deethylation whereas phenobarbital (80 mg/kg) was without effect. Furthermore, benzphetamine-N-demethylase could not be detected in rat renal microsomes. These data suggest that the composition of renal cytochromes P-450 may vary between species. {alpha}-Naphthoflavone inhibited both ethoxyresorufin and ethoxycoumarin metabolism by rat and rabbit renal microsomes; inhibition was highly selective for renal microsomes from ß-naphthoflavone-treated animals. Metyrapone did not inhibit rat renal microsomal mixed function oxidases from any treatment group. In contrast, rabbit renal microsomal xenobiotic metabolism from all treatment groups were strongly inhibited by metyrapone. Furthermore, polyacrylamide gel electrophoresis of solubilized renal microsomes from rabbits treated with phenobarbital revealed a new coomassie blue staining band in the range of 50000–60000 daltons; no such pattern was observed in rats. Electrophoresis of solubilized renal microsomes from both rats and rabbits treated with ß-naphthoflavone revealed increased Coomassie blue staining. It is apparent from these results that the rat kidney lacks any phenobarbital inducible form of cytochrome P-450 and that rat renal microsomes contain at least two forms of cytochrome P-450 whereas rabbit renal microsomes contain at least three forms.


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