The effect of taurine on the cholestatic potential of sulfated lithocholate and its conjugates.
The present study was aimed at determining whether the protection by taurine of lithocholate-sulfate-induced cholestasis is mediated by conjugation or by direct effect of the amino acid on bile formation. Injection of free and conjugated (glycine and taurine) sulfated lithocholate in guinea pigs significantly reduced the secretion rate of non-sulfated bile acids in bile. There was no decrease in bile flow after the injection of taurine-conjugated sulfated lithocholate, which was completely recovered in bile within 60 min. In contrast, injection of sulfated lithocholate and its glycine conjugate led to a marked decrease in bile flow, and neither one was significantly recovered in bile. In addition, both caused morphological changes in the liver, characterized by the accumulation of cytoplasmic vacuoles with lamellated myelin figures characteristic of phospholipidosis. Pretreatment with taurine (0.5% in drinking water for 3 days) prevented both the drop in bile flow and the histological changes in the liver, suggesting that conjugation with taurine removed the cholestatic potential of sulfated lithocholate. However, since taurine was effective not only in preventing cholestasis induced by the free form of sulfated lithocholate but also against its glycine conjugate, these results suggest that other mechanisms in addition to conjugate must be involved.
Belli
D C
DC
Department of Pediatrics, University of Montreal, Quebec, Canada.
Roy
C C
CC
Fournier
L A
LA
Tuchweber
B
B
Giguère
R
R
Yousef
I M
IM
D000818:Animals; D001646:Bile / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism; D002779:Cholestasis / Q000139:chemically induced* / Q000473:pathology; D006168:Guinea Pigs; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008297:Male; D013654:Taurine / Q000494:pharmacology*; D013658:Taurolithocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; C014202:sulfolithocholic acid; D013654:Taurine; D013658:Taurolithocholic Acid; D008095:Lithocholic Acid; C027746:glycolithocholic acid