Abstract
In previous papers, it was reported that the activity of drug-metabolizing enzymes of liver microsomes was decreased in alloxan diabetic or fasted male rats (1, 2). The hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes were decreased in these animals, but the aniline and zoxazolamine hydroxylations were not decreased. In contrast to the results obtained with male rats, the hexobarbital hydroxylation and aminopyrine N-demethylation were not decreased in the microsomes from female rats. These results thus appeared to be related to the fact that the hexobarbital hydroxylation and aminopyrine N-demethylation are markedly stimulated by androgen, whereas the aniline and zoxazolamine hydroxylations are not stimulated (1, 2). From these results and others, it has been supposed that the decrease in the hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes from alloxan diabetic or fasted male rats is due to an impairment of the mechanism of androgen-dependent stimulation for these oxidative activities (1, 2).
On the other hand, the hexobarbital hydroxylation and aminopyrine N-demethylation by liver microsomes of mice and rabbits were not stimulated by androgen, and the lack of the androgen-dependent stimulating mechanism for the drug-metabolizing enzymes has been suggested (3, 4). Therefore, it is reasonable to speculate that, if the decrease in the hexobarbital hydroxylation and aminopyrine N-demethylation by the microsomes from alloxan diabetic or fasted male rats is due to an impairment of the androgen-dependent stimulating mechanism, the decrease in the oxidative activity does not occur in male mice and rabbits and that the sex difference in the alteration of drugmetabolizing enzymes due to alloxan diabetes or starvation is not observed in the liver microsomes from mice and rabbits.
In the present studies, these possibilities were investigated through comparative studies on the effect of alloxan diabetes and starvation on the liver microsomes of both sexs of rats, mice and rabbits.
