The effect of taurine on the cholestatic potential of sulfated lithocholate and its conjugates

Authors

  • Dominique C. Belli,

    1. Departments of Pediatrics, University of Montreal, Montreal, Quebec, Canada
    2. Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Montreal, Quebec, Canada
    Search for more papers by this author
  • Claude C. Roy M.D.,

    Corresponding author
    1. Departments of Pediatrics, University of Montreal, Montreal, Quebec, Canada
    2. Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Montreal, Quebec, Canada
      Centre de Recherche Pédiatrique Hôpital Sainte-Justine 3175 Ch. Côte Ste-Catherine Montreal, Québec H3T 1C5
    Search for more papers by this author
  • Lyse-Andrée Fournier,

    1. Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Montreal, Quebec, Canada
    Search for more papers by this author
  • Beatriz Tuchweber,

    1. Departments of Nutrition, University of Montreal, Montreal, Quebec, Canada
    2. Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Montreal, Quebec, Canada
    Search for more papers by this author
  • Robert Giguère,

    1. Department of Pediatrics, University of Sherbrooke, Montreal, Quebec, Canada
    Search for more papers by this author
  • Ibrahim M. Yousef

    1. Departments of Pharmacology, University of Montreal, Montreal, Quebec, Canada
    2. Centre de Recherche Pédiatrique, Hôpital Sainte-Justine, Montreal, Quebec, Canada
    Search for more papers by this author

Centre de Recherche Pédiatrique Hôpital Sainte-Justine 3175 Ch. Côte Ste-Catherine Montreal, Québec H3T 1C5

Abstract

ABSTRACT— 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.

Ancillary