Ethyl Pyruvate Ameliorates Renal Ischemia- reperfusion Injury

Purpose: Reactive oxygen species (ROS) significantly contribute to ischemia-reperfusion injury, and are also associated with the gradual loss of renal function and renal failure following renal transplantation. Pyruvate is an endogenous antioxidant, but its use as a therapeutic agent for treating conditions mediated by oxidative stress is limited due to its poor stability in solution. However, ethyl pyruvate (EP), a soluble pyruvate derivative, has far greater stability than pyruvate; thus, may serve as a practical pyruvate precursor. Therefore, the ability of EP in the prevention of renal ischemia-reperfusion injury was assessed. Methods: Sprague-Dawley rats (n=54) were subjected to 40 minutes of renal warm ischemia. The animals were divided into three groups: the sham group without warm ischemia (n=18), the EP group (n=18, EP given before ischemia), and the ischemic control (n=18). The serum levels of creatinine and TNF-α were measured 1, 3 and 5 days after induction of ischemia. The expression of high mobility group box-1 (HMGB-1), a delayed inflammatory mediator, was also assessed by Western blot of renal specimens. Results: In the EP group, late improvements in the serum levels of creatinine and TNF-α were observed in comparison with the ischemic control. Based on this delayed effect, the expression of HMGB-1 was assessed in renal tissue. The HMGB-1 expression increased over time during the ischemia process, but EP suppressed this expression 3 and 5 days after renal ischemia-reperfusion injury. Conclusion: These results have demonstrated, for the first time, that EP ameliorates renal ischemia-reperfusion injury. EP attenuates the renal ischemia-reperfusion injury, at least in part, by suppressing the expression of HMGB-1, a late mediator of delayed inflammation.ope