EFFECT OF STARVATION ON THE IN VIVO METABOLISM AND EFFECT OF DRUGS IN FEMALE AND MALE RATS

Abstract

The enzymes which metabolize lipid soluble compounds are localized in microsomes of liver and reduced NADP and molecular oxygen are required as cofactors. It was recently demonstrated that the activities of drug-metabolizing enzymes are an important factor for controling the action and toxicity of drugs (1-9). The activities of drugmetabolizing enzymes were altered by several factors, such as administration of some drugs, anabolic hormone, alloxan diabetes, hyperthyroidism and starvation (1-15). In previous papers, it was reported that the activity of drug-metabolizing enzymes of liver microsomes in male rats was markedly decreased by starvation, while the activity in female rats was increased (14). The starvation caused a decrease in liver weight as well as body weight and the blood flow of liver. On the other hand, studies on electron microscopy showed that endoplasmic reticulum in liver of fasted rats was markedly altered in their fine structure by starvation (16, 17). Moreover, it has been considered that microsomes are artifacts during the homogenization of liver and they are likely derived from the endoplasmic reticulum. Thus, there is a possibility that the alternations in the enzyme activities in female and male rats may be artifacts during the homogenization. The purpose of the present investigation is to establish the correlation between the in vivo metabolism and activity of drugs and the in vitro metabolism of drugs in fasted female and male rats.