Reduced bile flow associated with parenteral nutrition is independent of oxidant load and parenteral multivitamins

Background: Reduction in bile flow is a characteristic of cholestasis related to parenteral nutrition. Light exposure of parenteral multivitamin preparations is the major source of peroxides contaminating parenteral nutrition solutions. They may contribute to local oxidative stress. Oxidants are reported to affect transport mechanisms across the hepatocyte membrane into bile. The authors hypothesize that an oxidant-antioxidant imbalance is involved in parenteral nutrition related cholestasis. The aim of this study was to investigate the roles of multivitamin preparations and peroxides on bile flow in newborn guinea pigs receiving parenteral nutrition. Methods: Three-day-old guinea pigs were fed enterally or parenterally with solutions containing 8% dextrose/0.45% NaCl +/- multivitamin preparation +/- amino acids +/- lipids. The influence of the oxidant-antioxidant balance on bile flow was evaluated using 500 mu M hydrogen peroxide and 1% and 3% multivitamin preparations +/- Na metabisulfite. Four days later, animals were anesthetized and bile flow was recorded over 2 hours. Glutathione determinations were performed on bile and liver samples. The percentage of oxidized glutathione, reflecting the redox status, was used as a marker of oxidative stress. Data were compared by analysis of variance with P < 0.05. Results: Bile flow decreased first on initiating dextrose + NaCl infusion (a 25% decrease) and subsequently by adding amino acids (a further 30% decrease). Although antioxidant vitamins and peroxides modified the hepatic redox status, they did not influence bile flow. Conclusion: Although the composition of parenteral nutrition affects bile flow and the hepatic redox status, the oxidant-antioxidant imbalance in infused solutions is not the causal event in the installation of cholestasis.