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Supplementary Material for: Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury

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posted on 2023-05-24, 13:28 authored by Hai-Yuan Xu, Wang Qiaoxuan, Sun Peng, Yang Zhongyuan
Introduction: Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is reno-protection in a post-IR porcine kidney model. Methods: We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intraarterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and post-operative tissue samples were analyzed by H&E histochemistry and immunohistochemistry. Results: Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation, with normal IL-6 and TLR4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule NHE3. Conclusions: Local, intrarenal post-ischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was reno-protective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation.


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    American Journal of Nephrology