TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCα-ezrin pathway

Leonardo Baiocchi, Giuseppe Tisone, Mario Antonio Russo, Chiara Longhi, Gianpiero Palmieri, Antonio Volpe, Cristiana Almerighi, Claudia Telesca, Marco Carbone, Luca Toti, Francesco De Leonardis, Mario Angelico

Research output: Contribution to journalArticle

Abstract

Cholestasis, induced by liver ischemia-reperfusion injury (IRI), is characterized by dilatation of bile canaliculi and loss of microvilli. Tauroursodeoxycholic acid (TUDCA) is an anti-cholestatic agent, modulating protein kinase C (PKC) α pathway. PKC reduces ischemic damage in several organs, its isoform α modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCα-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 °C for 6 h) were reperfused (37 °C with O2) with Krebs-Ringer bicarbonate + 2.5 μmol/min of Taurocho-late or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCα and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCα inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25 ± 0.17 vs. 0.042 ± 0.02 μl/min/g liver, P <0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCα and ezrin expression (P = 0.03 and P = 0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCα inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCα-ezrin pathway.

Original languageEnglish
Pages (from-to)792-800
Number of pages9
JournalTransplant International
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Cholestasis
  • Injury
  • Ischemia-reperfusion
  • Liver
  • Tauroursodeoxycholic acid

ASJC Scopus subject areas

  • Transplantation

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    Baiocchi, L., Tisone, G., Russo, M. A., Longhi, C., Palmieri, G., Volpe, A., Almerighi, C., Telesca, C., Carbone, M., Toti, L., De Leonardis, F., & Angelico, M. (2008). TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCα-ezrin pathway. Transplant International, 21(8), 792-800. https://doi.org/10.1111/j.1432-2277.2008.00682.x