BILE-ACIDS PROTECT THE LIVER AGAINST THE CHOLESTATIC EFFECT OF LARGE BILIRUBIN LOADS

Background: This study was undertaken to elucidate why large bilirubin loads cause canalicular cholestasis and whether bile acid infusions p rotect against bilirubin-induced cholestasis. Methods: The effects of bilirubin infusion on canalicular bile secretion and canalicular membr ane morphology were studied in bile acid-depleted pigs (BADP), bile ac id-primed pigs (BAPP), and pigs co-infused with bile acids during bili rubin loading (BACIP). Results: Bilirubin caused complete cholestasis in BADP, 38% bile flow reduction in BAPP, and no effect on bile flow i n BACIP. Scanning electron micrographs showed loss of 70% of canalicul ar microvilli in BADP, 13% loss and pathologic changes in the remainin g 75% of microvilli in BAPP, and no canalicular changes in BACIP. Chol estasis was not due to hydromechanical obstruction of bile ductules or bile Ca2+ depletion. Conclusion: Bilirubin causes cholestasis in BADP by injuring canalicular microvilli. Intravenous glycocholate infusion s fully protect the liver against bilirubin-induced cholestasis and ca nalicular microvillar injury.