Decreased effect of phenobarbital treatment on microsomal drug metabolizing enzyme activity during gestation.

Abstract

Pregnant and nonpregnant rats were treated with 37.5 mg phenobarbital (PB) per kg body weight twice daily for 4 days. Pregnant rats were injected with PB from day 10 to day 13 and from day 17 to day 20 of gestation and were used for the experiments on day 14 or day 21, respectively. This treatment resulted in a 35% increase in liver weight in nonpregnant rats. The livers of pregnant rats weighed the same as the livers from PB-treated nonpregnant rats, and PB-treatment during gestation had only a small stimulatory effect on liver weight.—The duration of sleeping time after an i.p. injection of 125 mg hexobarbital per kg maternal body weight was identical in control nonpregnant and control pregnant rats. PB-treatment significantly reduced the sleeping time but PB-treated pregnant rats had a longer sleeping time than PB-treated nonpregnant rats.—In liver microsomes, the K m and V max values were measured for the ethylmorphine N-demethylase and benzo(a)pyrene hydroxylase. For the two substrates the K m values were identical in all groups. The V max values for the two enzyme activities were not different in control pregnant and control nonpregnant rats when calculated per total liver. Treatment of the rats with PB increased the V max values for the two enzyme activities, but these values were significantly lower in the microsomes obtained from PB-treated pregnant rats.—The content of cytochrome P-450 was higher in PB-treated nonpregnant rats than in control nonpregnant rats, but no increase in the amount of cytochrome P-450 was measured after treating pregnant rats with PB.—The electron microscopic examination of the livers of pregnant rats revealed that the smooth elements of the endoplasmic reticulum were predominant in the cytoplasm, and after PB-treatment the typical proliferation of the smooth ER was not detectable.