Background Donation after Cardiac Death (DCD) liver graft can provide possible and practical solutions to the organ shortage crisis, but extended warm ischemia time aggravates the organ injury. Ischemia reperfusion injury can induce ER stress and lead to cell death. Tauroursodeoxycholic acid (TUDCA) has effect of prevent hepaticullar apoptosis induced by ER stress. Herein, we tested the protective effects and mechanism of TUDCA to alleviate ischemia-reperfusion injury in DCD rat liver transplantation.

Methods Male Sprague-Dawley (SD) rats were separated into three groups: 1) Liver transplantation group (F group). Grafts were cold-stored in UW solution after organ harvest; 2) DCD liver group (D group).Cardiac arrest was induced one hour before organ harvest, and the other treatment was similar to F group; 3) TUDCA (12.5, 25, 50 and 100 mg/L) treated group (T group). TUDCA was dissolved in UW solution. After cold-storage (24 hours), different UW solution was tested for ALT and AST. 24 hours after liver transplantation, blood samples were taken for ALT, AST and TBIL tests; H-E and TUNEL staining of livers were performed; and liver NF-ΚB, XBP-1, EIF2AK3, Caspases (3, 8, 9 and 12), P38, ERK MAPK, PI3K, TNF-Α, and IL-1beta levels were analyzed by RT-PCR and immunoblotting.

Results In vitro and in vivo studies demonstrated that ALT and AST levels were significantly higher in D group than F group. 50 mg/L of TUDCA is an ideal concentration to alleviate liver IR injury in DCD. This protection was dependent on activation of P38, ERK MAPK, and PI3K pathways, but independent of competition on the cell membrane, NF-ΚB activation, and transcription.

Conclusions In summary, these data depicted a pivotal role of ER stress in ischemia-reperfusion injury of DCD liver transplantation, suggesting the therapeutic potential of ER stress as a target in the management of DCD liver transplantation.

« Back to 2013 American Transplant Congress