Tauroursodeoxycholate ameliorates reperfusion injury after pig liver transplantation.
Reperfusion injury is a serious problem after clinical liver transplantation, often leading to dys- or even non-function of grafts. The present study was designed to determine whether the hydrophilic bile salt tauroursodeoxycholate (TUDC), known to be hepatoprotective in cholestatic liver disease, mitigates reperfusion injury in an in vivo pig liver transplantation model. Liver transplantation was performed in 12 pigs after a preservation time of 8 h. TUDC was administered to donor and recipient animals, and saline to controls. Blood was drawn at different time points for determination of liver enzymes. Bile samples were collected, and bile flow (BF), and bile salt secretion rate (BSSR) determined. Samples of liver tissue and bile ducts were taken for assessment by light and electron microscopy. Liver enzymes were significantly lower in the TUDC group. BF and BSSR were significantly higher. Microscopy revealed better preservation of bile duct architecture of the TUDC-infused animals. We can conclude that infusions of TUDC in pig livers ameliorate reperfusion injury in vivo. The molecular basis for this finding may be the membrane stabilizing effect of TUDC. Further studies are warranted to clarify its effect.
Hertl
M
M
Department of General and Transplantation Surgery, University Hospital Essen, Germany.
Hertl
M C
MC
Kunkel
P
P
Schilling
S
S
Prevot
B
B
Kluth
D
D
Malagó
M
M
Broelsch
C E
CE
D000818:Animals; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D011183:Postoperative Complications; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D013552:Swine; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D016572:Cyclosporine