Ursodeoxycholate further increase bile-duct cell proliferative response induced by partial bile-duct ligation in rats

Michele Barone, Eugenio Maiorano, Roberta Ladisa, Antonia Pece, Pasquale Berloco, Mario Strazzabosco, Maria Lucia Caruso, Anna Maria Valentini, Enzo Ierardi, Alfredo Di Leo, Antonio Francavilla

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Background: Bile salts (BSs) stimulate cholangiocyte proliferation in vitro and in vivo in normal rats. In this study, we evaluated the effects of BS-enriched diets on cholangiocyte proliferative activity already triggered by partial bile-duct ligation (pBDL), a surgical model that induces mild cholestatic conditions, focusing our attention on ursodeoxycholate (UDC). Methods: Animals (n=45) were fed either a standard diet, or a 0.2% deoxycholate- or 0.2% UDC-enriched diet for 4 weeks. Then, in each group, ten animals underwent pBDL and five underwent sham operation. Serum and biliary BS levels, serum cholestasis and cytolysis indexes, as well as liver conventional histology, apoptosis and proliferative activity were evaluated 48 h after the operation. Results: Animals that underwent pBDL showed sustained proliferative response compared with sham-operated rats. BS-enriched diets did not influence cholangiocyte proliferation in sham-operated rats. However, significantly increased proliferation was observed in pBDL rats fed a UDC-enriched diet. The evaluation of humoral and histological parameters excluded the possibility that the increased proliferation induced by UDC-enriched diet could be related to concomitant liver cell damage. Conclusion: A UDC-enriched diet is able to amplify the magnitude of the cholangiocyte hyperplastic process, which occurs by a stimulatory mechanism after partial bile-duct ligation.

Original languageEnglish
Pages (from-to)554-560
Number of pages7
JournalVirchows Archiv
Issue number6
Publication statusPublished - Jun 2004



  • Bile salts
  • Cholangiocyte proliferation
  • Cholestasis
  • Partial bile-duct ligation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Barone, M., Maiorano, E., Ladisa, R., Pece, A., Berloco, P., Strazzabosco, M., Caruso, M. L., Valentini, A. M., Ierardi, E., Di Leo, A., & Francavilla, A. (2004). Ursodeoxycholate further increase bile-duct cell proliferative response induced by partial bile-duct ligation in rats. Virchows Archiv, 444(6), 554-560.