TARGETING HIGH MOBILITY GROUP BOX 1 WITH INHIBITORS ATTENUATE ACUTE KIDNEY INJURY IN POSTISCHEMIC KIDNEYS

Abstract Background and Aims HMGB1 (high mobility group box 1) is released from dying cells and hence works as a danger signal, which amplifies necroinflammation in postischemic acute kidney injury. If and to what extend small molecule HMGB1 inhibitors are capable to ameliorate the acute kidney injury is still unknown. Method Mice underwent 17 min unilateral renal ischemia followed by reperfusion (IR) for 4 or 7 days and were administered either 50 mg/kg glycyrrhizic acid, 80 mg/kg ethyl pyruvate, or PBS i.p. 1h before surgery and once daily until day 7. Results Administration of HMGB1 inhibitors consistently increased the glomerular infiltration rate at day 4 and day 7, in parallel with a reduction of plasma creatinine and circulating HMGB1 at day 7 of reperfusion. Histopathological analysis confirmed that HMGB1 inhibitors consistently attenuated tubule injury. In vitro, HMGB1 inhibitors protected primary murine tubular epithelial cells against H2O2-induced cell death. Conclusion Our data indicate that the treatment with glycyrrhizic acid or ethyl pyruvate ameliorates post-ischemic renal injury. This serves as a rationale to further study the role of extracellular HMGB1 and its inhibition in different models of acute kidney injury.