THE ENHANCED EFFECT OF PARENTERAL-NUTRITION ON HEPATOTOXICITY

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral f eedings. In this study, we hypothesized that (1) route of feeding affe cts morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Ent eral), (3) standard total parenteral nutrition infused via a central c atheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), an d (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was n ot manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to signifi cantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level afte r 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had les s morbidity than TPN but greater morbidity than Chow. Addition of poly myxin B or glutamine had a minimal effect on morbidity or mortality wh en compared to the TPN group. We conclude that rats receiving IV nutri tion have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.