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 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.


CONCLUSIONS
Bilirubin causes cholestasis in BADP by injuring canalicular microvilli. Intravenous glycocholate infusions fully protect the liver against bilirubin-induced cholestasis and canalicular microvillar injury.
Villanger
O
O
Institute for Experimental Medical Research, University of Oslo, Norway.
Bjørnbeth
B A
BA
Lyberg
T
T
Raeder
M G
MG
D000818:Animals; D001647:Bile Acids and Salts / Q000627:therapeutic use*; D001648:Bile Canaliculi / Q000473:pathology*; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006932:Hyperbilirubinemia / Q000150:complications*; D007262:Infusions, Intravenous; D008297:Male; D013552:Swine
D001647:Bile Acids and Salts