EFFECT OF PHENOBARBITAL ON THE ACTIVITIES OF DRUG-METABOLIZING ENZYMES AND ELECTRON TRANSPORT SYSTEM OF LIVER MICROSOMES IN ALLOXAN DIABETES AND THYROXINE TREATED RATS

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Abstract
The administration of phenobarbital markedly increased the activities of drug-metabolizing enzymes and NADPH-linked electron transport system of liver microsomes (1-4). Moreover, the administration of phenobarbital increased the amount of liver microsomal protein and the incorporation of amino acid into liver microsomal protein (5, 6). The effects of phenobarbital to induce the activities of drug-metabolizing enzymes in tumor-bearing rats and immature rats were higher than those in normal rats and mature rats (7, 8). These results suggest that the effect of phenobarbital to induce the activities of drug-metabolizing enzymes may be related to the rate of biosynthesis of protein in liver microsomes. In a previous paper, it was reported that the activities of drug-metabolizing enzymes in alloxan diabetic and thyroxine-treated male rats were decreased, while the same activities in female rats were slightly increased. The decrease in the activities in male rats seemed to be due to an interference in the androgen-dependent stimulation (9). It is well known that the incorporation of amino acid into liver microsomal protein is decreased in alloxan diabetic rats, while the incorporation is increased in thyroxinetreated rats (10-12). Thus, the purpose of present studies was to investigate whether the effect of phenobarbital to induce the activities of drug-metabolizing enzymes and NADPH-linked electron transport system is increased in thyroxine-treated rats and decreased in alloxan diabetic rats.