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) alpha pathway. PKC reduces ischemic damage in several organs, its isoform alpha modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCalpha-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 degrees C for 6 h) were reperfused (37 degrees C with O(2)) with Krebs-Ringer bicarbonate + 2.5 micromol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCalpha and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCalpha inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25+/-0.17 vs. 0.042+/-0.02 microl/min/g liver, P<0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCalpha and ezrin expression (P=0.03 and P=0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCalpha inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCalpha-ezrin pathway.

Baiocchi, L., Tisone, G., Russo, M.a., Longhi, C., Palmieri, G., Volpe, A., et al. (2008). TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKC alpha-ezrin pathway. TRANSPLANT INTERNATIONAL, 21(8), 792-800 [10.1111/j.1432-2277.2008.00682.x].

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

BAIOCCHI, LEONARDO;TISONE, GIUSEPPE;RUSSO, MARIO ANTONIO;PALMIERI, GIAMPIERO;VOLPE, ANTONIO;TOTI, LUCA;ANGELICO, MARIO
2008-08-01

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) alpha pathway. PKC reduces ischemic damage in several organs, its isoform alpha modulates ezrin, a key protein in the maintenance of cell lamellipoidal extensions. We evaluated the effects of TUDCA on cholestasis, canalicular changes and PKCalpha-ezrin expression in a rat model of liver IRI. Livers flushed and stored with Belzer solution or Belzer + 10 mm TUDCA (4 degrees C for 6 h) were reperfused (37 degrees C with O(2)) with Krebs-Ringer bicarbonate + 2.5 micromol/min of Taurocholate or TUDCA. Bile was harvested for bile flow assessment. Liver tissue was employed for Electron Microscopy (EM) and for PKCalpha and ezrin immunoblot and immunofluorescence. The same experiments were conducted with the PKCalpha inhibitor Go-6976. TUDCA-treated livers showed increased bile flow (0.25+/-0.17 vs. 0.042+/-0.02 microl/min/g liver, P<0.05) and better preservation of microvilli and bile canalicular area at EM. These effects were associated with increased PKCalpha and ezrin expression (P=0.03 and P=0.04 vs. control respectively), as also confirmed by immunofluorescence data. PKCalpha inhibition abolished these TUDCA effects. TUDCA administration during IRI reduces cholestasis and canalicular damage in the liver modulating PKCalpha-ezrin pathway.
ago-2008
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/17 - ISTOLOGIA
Settore MED/12 - GASTROENTEROLOGIA
Settore MED/18 - CHIRURGIA GENERALE
English
Con Impact Factor ISI
Carbazoles; Animals; Taurochenodeoxycholic Acid; Cholestasis; Protein Kinase C-alpha; Enzyme Inhibitors; Rats; L-Lactate Dehydrogenase; Bile Canaliculi; Bile; Cholagogues and Choleretics; Rats, Wistar; Liver; Cytoskeletal Proteins; Male; Reperfusion Injury; Microscopy, Electron, Scanning
Baiocchi, L., Tisone, G., Russo, M.a., Longhi, C., Palmieri, G., Volpe, A., et al. (2008). TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKC alpha-ezrin pathway. TRANSPLANT INTERNATIONAL, 21(8), 792-800 [10.1111/j.1432-2277.2008.00682.x].
Baiocchi, L; Tisone, G; Russo, Ma; Longhi, C; Palmieri, G; Volpe, A; Almerighi, C; Telesca, C; Carbone, M; Toti, L; De Leonardis, F; Angelico, M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/67045
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