The Effects of Cyclooxygenase (COX)-2 Inhibition on Ischemia-Reperfusion Injury in Liver Transplantation

Abstract

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°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 B2 (TxB2) 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 TxB2 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.