Effect of protein depletion and intrauterine growth retardation on rat hepatic drug metabolism.

Abstract

The effect of intrauterine malnutrition in rats on in vivo and in vitro drug metabolism at weaning was investigated. We have employed two experimental designs to produce intrauterine malnutrition, maternal dietary protein depletion starting at day 7 of gestation and unilateral ligation of the uterine artery on day 17 of gestation. At birth cross-fostering of newborns was done, experimental and control group of litters raised separately until weaning (21 days of age). Both methods produced offspring with lower body and liver weights and these changes were present at weaning. However, only in the protein-restricted group were significant differences for liver:body weight ratio and hepatic microsomal protein content observed. Liver microsomal cytochrome P-450 and b5 contents were significantly decreased in small animals from mothers with intrauterine vessels ligated but not in the prenatal protein-restricted group. A significant increase in aminopyrine N-demethylase and a decrease in aniline hydroxylase enzyme activities was observed in both experimental groups. No significant differences were found in reductive or conjugative pathways of drug metabolism. Hexobarbital sleeping time was significantly increased in weanling animals from the prenatal protein-restricted mothers but not in the uterine-vessels-ligated group. These results suggest that maternal malnutrition may play an important role in modulation of postnatal drug metabolism pattern of progeny.