Intravenous ursodeoxycholic acid reduces cholestasis in parenterally fed newborn piglets.
OBJECTIVE
Cholestasis complicates total parenteral nutrition (TPN) in preterm infants. Ursodeoxycholic acid (UDCA) is used for several cholestatic problems. The hypothesis of this study was that intravenous 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 triphosphatase (ATPase) activity.


METHODS
Three groups of piglets were studied: group 1 received sow's milk, groups 2 and 3 received TPN, and group 3 also received 100 mumol.kg-1.day-1 UDCA intravenously. After 3 weeks, basal and stimulated bile flow were measured. Cholesterol, bile acids, phospholipids, and phospholipid fatty acids were analyzed in bile, and fluidity, phospholipid fatty acid composition, and Na+,K(+)-ATPase were analyzed in hepatocyte membranes.


RESULTS
Bile acid secretion 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. Sinusoidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals. UDCA also increased Na+,K(+)-ATPase activity. Bile and membrane phospholipid fatty acids reflected dietary fatty acids.


CONCLUSIONS
Intravenous UDCA improves bile flow and reduces bilirubin levels in the serum and liver in piglets with TPN-induced cholestasis.
Duerksen
D R
DR
Department of Medicine, University of Alberta, Edmonton, Canada.
Van Aerde
J E
JE
Gramlich
L
L
Meddings
J B
JB
Chan
G
G
Thomson
A B
AB
Clandinin
M T
MT
D000818:Animals; D000831:Animals, Newborn; D001646:Bile / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002779:Cholestasis / Q000517:prevention & control*; D007275:Injections, Intravenous; D008055:Lipids / Q000032:analysis; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
D008055:Lipids; D014580:Ursodeoxycholic Acid; D000254:Sodium-Potassium-Exchanging ATPase