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 feedings. In this study, we hypothesized that (1) route of feeding affects 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 (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly 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 after 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 less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition 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.