Biliary lithocholate and cholestasis during and after total parenteral nutrition: an experimental study.
To evaluate the role of lithocholic acid (LCA) in the etiology of parenteral nutrition-associated cholestasis (PN-AC), we studied (i) the changes in the percentage of biliary LCA and (ii) the emergence and resolution of cholestatic changes in the liver after total parenteral nutrition (TPN) and after 6 weeks of oral feeding following the TPN. We compared these changes in rabbits on TPN support (via a central vein) for 14 days (TPN, n = 8) with those after 6 weeks of refeeding (Post-TPN, n = 8). Age-matched rabbits on lab chow served as controls (CHOW, n = 8). At the end of the diet regimens, the common bile duct was cannulated under anesthesia, and hepatic bile collected for measurements of bile flow and bile acid (BA) secretion rates, and BA profiles. The 60-min biliary excretion of sulfobromophthalein (BSP) after an intravenous bolus (5 mg/kg) was determined. A liver biopsy was taken for light microscopy. After 14 days of TPN, bile flow was reduced by 60%, bile acid secretion by 52%, and BSP excretion by 38%. On refeeding, only the BSP excretory rate recovered fully. In the TPN group, histology of the liver showed hepatocellular degeneration and portal tract inflammation; these resolved after refeeding leaving a mild portal fibrosis in 4/8 rabbits. Total colonic stasis occurred during TPN. With TPN, a decrease in the percentage of biliary glycochenodeoxycholate and an increase in LCA% were seen, whereas after refeeding the increase was in the percentage of glycoursodeoxycholate. An LCA% > or = 6 was associated with liver cell damage. After 6 weeks of refeeding, the structural cholestasis disappeared, but the decreases in basal bile flow and bile acid secretion (functional cholestasis) persisted. These data associate an increase in biliary LCA with the emergence of cholestasis during TPN in rabbits.
Das
J B
JB
Pediatric Surgical Research Laboratory, Children's Memorial Hospital, Chicago, Ilinois 60614, USA.
Uzoaru
I L
IL
Ansari
G G
GG
D000818:Animals; D001646:Bile / Q000737:chemistry; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology*; D004750:Enteral Nutrition; D005260:Female; D007202:Indicators and Reagents; D008095:Lithocholic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010289:Parenteral Nutrition, Total; D011817:Rabbits; D013448:Sulfobromophthalein / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D007202:Indicators and Reagents; D013448:Sulfobromophthalein; D008095:Lithocholic Acid