INTRAVENOUS URSODEOXYCHOLIC ACID REDUCES CHOLESTASIS IN PARENTERALLY FED NEWBORN PIGLETS

Background & Aims: Cholestasis complicates total parenteral nutrition (TPN) in preterm infants, Ursodeoxycholic acid (UDCA) is used for seve ral cholestatic problems, The hypothesis of this study was that intrav enous UDCA prevents TPN-induced cholestasis by (1) maintaining normal basal and stimulated bile flow, (2) altering bile composition, and (3) changing hepatocyte membrane composition and Na+,K+-adenosine triphos phatase (ATPase) activity. Methods: Three groups of piglets were studi ed: group 1 received sow's milk, groups 2 and 3 received TPN, and grou p 3 also received 100 mu mol . kg(-1) . day(-1) UDCA intravenously, Af ter 3 weeks, basal and stimulated bile flow were measured, Cholesterol , bile acids, phospholipids, and phospholipid fatty acids were analyze d in bile, and fluidity, phospholipid fatty acid composition, and Na+, K+-ATPase were analyzed in hepatocyte membranes. Results: Bile acid se cretion and basal and stimulated bile flow were similar in control and UDCA-treated animals but reduced to <50% in the TPN group, Bile acid- dependent and -independent bile flow were lower in the TPN group, UDCA did not normalize abnormalities in TPN-induced bile composition, Sinu soidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals, UDCA also increased Na+,K+-ATPas e activity. Bile and membrane phospholipid fatty acids reflected dieta ry fatty acids, Conclusions: Intravenous UDCA improves bile flow and r educes bilirubin levels in the serum and liver in piglets with TPN-ind uced cholestasis.