Academic Journal
Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury
| العنوان: | Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury |
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| المؤلفون: | Jonas, Michael, Simon, Amos J., Gilburd, Boris, Schneiderman, Jacob |
| المصدر: | American Journal of Nephrology ; volume 54, issue 7-8, page 337-348 ; ISSN 0250-8095 1421-9670 |
| بيانات النشر: | S. Karger AG |
| سنة النشر: | 2023 |
| الوصف: | 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 renoprotective 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 intra-arterial 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 postoperative tissue samples were analyzed by hematoxylin and eosin 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 tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3. Conclusions: Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1159/000531174 |
| DOI: | 10.1159/000531174/4043501/000531174.pdf |
| الاتاحة: | http://dx.doi.org/10.1159/000531174 https://karger.com/ajn/article-pdf/doi/10.1159/000531174/4043501/000531174.pdf |
| Rights: | https://karger.com/pages/terms-and-conditions ; https://karger.com/pages/terms-and-conditions |
| رقم الانضمام: | edsbas.8730CD82 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1159/000531174 |
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