METABOLISM OF DRUGS IN OLD RATS (I) ACTIVITIES OF NADPH-LINKED ELECTRON TRANSPORT AND DRUG-METABOLIZING ENZYME SYSTEMS IN LIVER MICROSOMES OF OLD RATS

Abstract

Many lipid soluble compounds are metabolized by liver microsomes in the presence of oxygen and NADPH (1, 2). It has been considered that NADPH oxidizing system of liver microsomes is the responsible component for the oxidation and reduction of drugs (1-3). The metabolisms (oxidation and reduction) of drugs by liver microsomes are altered by diet, age and sex as well as by some unphysiological conditions (4-8). The alterations in the metabolisms of drugs are often accompanied with similar alterations in the activities of NADPH-linked electron transport system of liver microsomes (3, 4, 8-10). In a previous paper we reported a marked age differences in the oxidation of drugs, such as, hexobarbital, pentobarbital, meprobamate and carisoprodol by liver microsomes in the female rats (6). The activities of drug oxidations are almost zero at the birth and then rapidly increased upto 30 days, but the activities again decreased slightly with maturing in female rats. On the other hand, the activities in male rats are still increased with maturing and then slightly decreased (11). The purpose of present studies is the determination of the activities of drug-oxidizing and -reducing systems in old rats (about 600 days old) in comparison with young adult rats (about 100 days old). Moreover, it is of interest to investigate whether or not decreased activities in drug-oxidation and -reduction in old rats is related to those of NADPH-linked electron transport systems of liver microsomes. Many activities of drug oxidation show a clear sex difference and the activities are dependent on male sex hormone (6, 12). In the present experiments, therefore, the male and female rats were used for the study of the effect of male sex hormone in old rats.