EFFECT OF ADMINISTRATION OF 3-AMINOTRIAZOLE ON THE ACTIVITY OF MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEMS OF RAT LIVER

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Abstract
The administration of phenobarbital and other drugs increases the activities of drug-metabolizing enzymes, NADPH dehydrogenase and NADPH-cytochrome c reductase of liver microsomes (1-4). Moreover, it was reported that the administration of phenobarbital also increased the amount of P-450 in liver microsomes (4-6), which is a haemoprotein pigment of microsomes and probably have an important role for the oxidation of drugs (4-10). Recently, Granick and Urata demonstrated that the administration of many drugs, including phenobarbital, markedly increased the activities of δ-amino levulonic acid synthetase and synthesis of porphyrine (11, 12). These results suggested that the increase in the activities of drug-metabolizing enzymes after the administration of phenobarbital may be due to the results of the increasing amount of P-450 through an increased synthesis of porphyrine. On the other hand, administration of 3-amino-1, 2, 4-triazole markedly depressed the activity of liver and kidney catalase (13, 14). The action of 3-aminotriazole on the activity of liver catalase is not yet clear, and some results indicate that 3-aminotriazole may inhibit δ-adminolevulonic acid dehydrase and other enzymes for the synthesis of porphyrine in liver (15, 16). Thus, the purpose of the present communication is to investigate the action of 3-aminotriazole on the induction of drug-metabolizing enzyme systems and the increase in the amount of P-450 content of liver microsomes by the administration of phenobarbital.