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Bile acids protect the liver against the cholestatic effect of large bilirubin loads
O Villanger1, B A Bjørnbeth, T Lyberg
1Institute for Experimental Medical Research, University of Oslo, Norway.
Background:
This study was undertaken to elucidate why large bilirubin loads cause canalicular cholestasis and whether bile acid infusions protect against bilirubin-induced cholestasis.
Methods:
The effects of bilirubin infusion on canalicular bile secretion and canalicular membrane morphology were studied in bile acid-depleted pigs (BADP), bile acid-primed pigs (BAPP), and pigs co-infused with bile acids during bilirubin loading (BACIP).
Results:
Bilirubin caused complete cholestasis in BADP, 38% bile flow reduction in BAPP, and no effect on bile flow in BACIP. Scanning electron micrographs showed loss of 70% of canalicular microvilli in BADP, 13% loss and pathologic changes in the remaining 75% of microvilli in BAPP, and no canalicular changes in BACIP. Cholestasis 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 infusions fully protect the liver against bilirubin-induced cholestasis and canalicular microvillar injury.