Effect of nicotinamide on drug metabolizing enzymes in the neonatal rat

Sprague-Dawley rats were raised by dams (mother reared, MR) or artificially reared from day 4 to day 11, using chronic intragastric cannulas, and infused with one of four diets: control (AR); or supplemented with nicotinamide-low (LN, 300 mg/l), medium (MN, 750 mg/l), or high (HN, 1500 mg/l). Liver to body weight ratios were higher in all artificially reared groups (AR, LN, MN, HN) compared to MR pups. The amount of recovered hepatic microsomal protein was lower in all artificially reared groups when compared with MR pups. Uridine diphosphoglucuronyl transferase activity with para-nitrophenol as the substrate (UDPGT-PNP) was greater in all of the artificially reared groups compared to the MR group. UDPGT-PNP activity in the HN group was greater than in the AR, LN, or MN groups. Cytochrome P-450 concentration was highest in the MR group, whereas there were no differences among the artificially reared groups. It was concluded that the artificial rearing process stimulated hepatic UDPGT-PNP activity and depressed cytochrome P-450 concentrations, whereas dietary supplementation with nicotinamide during the preweanling period resulted in a further increase in UDPGT-PNP activity.