EFFECTS OF ARTIFICIAL REARING AND NICOTINAMIDE SUPPLEMENTATION ON DRUG METABOLISM IN RATS
Abstract
Large doses of nicotinamide administered by intraperitoneal injection or ingested orally have been reported to cause the induction of several hepatic drug metabolizing enzymes in adult rats. The effect of dietary nicotinamide supplementation on the drug metabolism capabilities of neonatal rats has not been investigated. Since the dietary intakes of preweanling rats cannot be controlled through manipulations of the dams' diet the method of chronic intragastric cannulation was employed. Intragastric cannulation enabled the rat pups to be reared away from the dams and provided control over the composition and amount of diet infused. Four day old Sprague-Dawley rats were fitted with gastric cannulas and infused with a control diet (AR) or the control diet supplemented with nicotinamide (LN = Low Nicotinamide 300 mg/l, MN = Medium Nicotinamide 750 mg/l, HN = High Nicotinamide 1500 mg/l). Rats were infused for 1 or 2 weeks. Mother Reared (MR) rats were used as controls. Eleven day old AR, LN, MN, and HN rats showed increased liver to body weight ratios, depressed cytochrome P-450 concentrations, and increased UDP-glucuronidation of para-nitrophenol (UDPGT-PNP) compared with mother reared controls. HN rats had the highest UDPGT-PNP of all the treatment groups. Eighteen day old AR and MN rats had increased liver to body weight ratios, but no difference in cytochrome P-450 concentrations or body weights compared to MR controls. MN rats glucuronidated PNP to a greater extent than MR and AR groups. MR, AR, and MN rats were weaned at age 21 days and raised until age 56 days. During the post weaning period half of the animals drank a 0.1% nicotinamide solution in place of drinking water. No differences were found between liver to body weight ratios and cytochrome P-450 concentrations. UDPGT-PNP was increased in MR and AR rats that drank nicotinamide supplemented water; however, MN rats showed no increase in UDPGT-PNP with or without continuous nicotinamide supplementation. Increased protein synthesis was examined as a possible mechanism for induction of UDPGT-PNP in 11 day old rats. MR and AR rats incorporated radiolabeled L-leucine to the same extent while HN rats showed depressed protein synthesis.
Degree
Ph.D.
Subject Area
Nutrition
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.