PURPOSE: Our objective was to evaluate whether COX-2 inhibition with FK3311, a selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function. METHODS: Inbred male Lewis rats weighing 200-260 g were used. The donor liver was perfused with cold University of Wisconsin (UW) solution and then stored in the same solution at 4 degrees C for 18 hr. After the preservation period, orthotopic liver transplantation was performed. Animals were divided into three groups: the control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow, and serum thromboxane B(2) (TxB(2)) levels were compared among groups. RESULTS: Survival rate was significantly better (p <. 05) and serum GOT levels 30 min after reperfusion were significantly lower (p <. 05) in the FK high-dose group compared to the other two groups. Four hours after reperfusion, GPT levels and liver tissue flow were significantly (p <. 05) better in the FK high-dose group compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB(2) levels were significantly lower in the FK high-dose group compared to the control (p <. 05). CONCLUSION: COX-2 activity results in deteriorated liver function after I/R injury associated with transplantation, and selective COX-2 inhibition improved liver graft function.
PURPOSE: Our objective was to evaluate whether COX-2 inhibition with FK3311, a selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function. METHODS: Inbred male Lewis rats weighing 200-260 g were used. The donor liver was perfused with cold University of Wisconsin (UW) solution and then stored in the same solution at 4 degrees C for 18 hr. After the preservation period, orthotopic liver transplantation was performed. Animals were divided into three groups: the control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow, and serum thromboxane B(2) (TxB(2)) levels were compared among groups. RESULTS: Survival rate was significantly better (p <. 05) and serum GOT levels 30 min after reperfusion were significantly lower (p <. 05) in the FK high-dose group compared to the other two groups. Four hours after reperfusion, GPT levels and liver tissue flow were significantly (p <. 05) better in the FK high-dose group compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB(2) levels were significantly lower in the FK high-dose group compared to the control (p <. 05). CONCLUSION:COX-2 activity results in deteriorated liver function after I/R injury associated with transplantation, and selective COX-2 inhibition improved liver graft function.
Authors: Naoko Kamo; Bibo Ke; Amir A Ghaffari; Xiu-da Shen; Ronald W Busuttil; Genhong Cheng; Jerzy W Kupiec-Weglinski Journal: Hepatology Date: 2013-05-15 Impact factor: 17.425
Authors: Kenya Yamanaka; Philipp Houben; Helge Bruns; Daniel Schultze; Etsuro Hatano; Peter Schemmer Journal: PLoS One Date: 2015-04-28 Impact factor: 3.240