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

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.