The Role of HMGB1 and the Effect of Ethyl Pyruvate on Ischemia and Reperfusion Injury of Rat Kidney

Chung, Ku Yong; Park, Jae Jeong; Kim, Yu Seun

Abstract

PURPOSE: High mobility group box-1 (HMGB1) was identified as a DNA binding protein that functions as a co-factor for proper transcriptional regulation in somatic cells. Extra- cellular HMGB1 acts as a potent pro-inflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. Ethyl pyruvate (EP), a stable aliphatic ester derived from pyruvic acid is the first described pharmacological inhibitor for HMGB1 secretion. We designed this study to identify the change of HMGB1 expression in rat kidney tissues of ischemia reperfusion injury and the effect of EP on the expression of HMGB1.
METHODS
Sprague-Dawley rats (200~300 g) were subjected to 40 minutes of renal warm ischemia. The animals were divided into three groups: sham group without warm ischemia, the EP group (EP given before ischemia), and the ischemic control group. Kidneys were harvested and serum creatinine, IL-1 and IL-6 were measured at 6hours, 1 day, 3 days and 5 days after reperfusion. Immunohistochemical stain of HMGB-1 was done.
RESULTS
Serum creatinine and IL-1 level were elevated in ischemic control group and EP injection group. In EP injection group, serum creatinine and IL-1 level were lower than the ischemic control group. In the rat 40minutes ischemia reperfusion model, HMGB1 expression was increased at 6 hours after reperfusion. which was decreased gradually at 1 day, 3 days, and 5 days after reperfusion. HMGB1 expression was more distinct at outer medullary area. intraperitoneal EP injection has no effect on the expression of HMGB1.
CONCLUSION
From these results, we deduced a conclusion that the preventive effect of EP on the rat kidney ischemia reperfusion injury is not by the decreased expression of HMGB1 but by the prevention of the release of the HMGB1.