J Korean Surg Soc.  2007 May;72(5):345-350.

Ethyl Pyruvate Ameliorates Renal Ischemia- reperfusion Injury

• Chung KY
• Jeong GY
• Ahn HJ
• Ju MK
• Chang HK
• Lee WJ
• Han PL
• Kim YS

Abstract

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-alpha 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-alpha 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.

Keyword

Ethyl pyruvate; High mobility group box-1; Renal ischemia-reperfusion

MeSH Terms

Animals
Blotting, Western
Creatinine
Inflammation
Ischemia
Kidney Transplantation
Oxidative Stress
Pyruvic Acid*
Rats, Sprague-Dawley
Reactive Oxygen Species
Renal Insufficiency
Reperfusion Injury*
Reperfusion*
Tumor Necrosis Factor-alpha
Warm Ischemia
Creatinine
Pyruvic Acid
Reactive Oxygen Species
Tumor Necrosis Factor-alpha