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 language | English |
|---|---|
| Pages (from-to) | 792-800 |
| Number of pages | 9 |
| Journal | Transplant International |
| Volume | 21 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2008 |
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Keywords
- Cholestasis
- Injury
- Ischemia-reperfusion
- Liver
- Tauroursodeoxycholic acid
ASJC Scopus subject areas
- Transplantation
Cite this
TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCα-ezrin pathway. / Baiocchi, Leonardo; Tisone, Giuseppe; Russo, Mario Antonio; Longhi, Chiara; Palmieri, Gianpiero; Volpe, Antonio; Almerighi, Cristiana; Telesca, Claudia; Carbone, Marco; Toti, Luca; De Leonardis, Francesco; Angelico, Mario.
In: Transplant International, Vol. 21, No. 8, 08.2008, p. 792-800.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TUDCA prevents cholestasis and canalicular damage induced by ischemia-reperfusion injury in the rat, modulating PKCα-ezrin pathway
AU - Baiocchi, Leonardo
AU - Tisone, Giuseppe
AU - Russo, Mario Antonio
AU - Longhi, Chiara
AU - Palmieri, Gianpiero
AU - Volpe, Antonio
AU - Almerighi, Cristiana
AU - Telesca, Claudia
AU - Carbone, Marco
AU - Toti, Luca
AU - De Leonardis, Francesco
AU - Angelico, Mario
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Cholestasis
KW - Injury
KW - Ischemia-reperfusion
KW - Liver
KW - Tauroursodeoxycholic acid
UR - http://www.scopus.com/inward/record.url?scp=52649174283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52649174283&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2008.00682.x
DO - 10.1111/j.1432-2277.2008.00682.x
M3 - Article
VL - 21
SP - 792
EP - 800
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 8
ER -