Enhancement of Microsomal Drug Hydroxylation and Glucuronidation in Rat Liver by Phenobarbital and 3‐Methylcholanthrene in Combination

Abstract:Both 3‐methylcholanthrene and phenobarbital increased the 0‐demethylation ofp‐nitroanisole in rat liver microsomes (9‐fold and 6‐fold, respectively), whereas 3‐methylcholanthrene alone was able to enhance the aryl hydrocarbon hydroxylase activity (13‐fold). When the inducers were administered to rats in combination, the enhancement inp‐nitroanisole 0‐demethylase activity was greater and in aryl hydrocarbon hydroxylase was smaller than when administered singly. Both 3‐methylcholanthrene and phenobarbital also enhanced the microsomal UDP glucuronyltransferase activity when measured afterin vitroactivation of the latent enzyme. The pretreatment of rats with the combination brought about no additional effect, when calculated on a microsomal protein basis. If calculated on 100 gram of body weight basis, however, an additive effect was observed in UDP glucuronyltransferase activity due to the effects of the inducers on the liver weight‐body weight ratio.