PMID- 37231766
OWN - NLM
STAT- MEDLINE
DCOM- 20231103
LR  - 20240218
IS  - 1421-9670 (Electronic)
IS  - 0250-8095 (Linking)
VI  - 54
IP  - 7-8
DP  - 2023
TI  - Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury.
PG  - 337-348
LID - 10.1159/000531174 [doi]
AB  - 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.
CI  - (c) 2023 S. Karger AG, Basel.
FAU - Jonas, Michael
AU  - Jonas M
AD  - Department of Cardiology, Kaplan Medical Center, Rehovot, Israel.
AD  - Hebrew University School of Medicine, Jerusalem, Israel.
FAU - Simon, Amos J
AU  - Simon AJ
AD  - Cancer Research Center, Institute of Hematology, Sheba Medical Center, Ramat Gan, 
      Israel.
FAU - Gilburd, Boris
AU  - Gilburd B
AD  - Autoimmunity Laboratory, Zabludowicz Center for Autoimmune Diseases, Sheba 
      Medical Center, Ramat Gan, Israel.
FAU - Schneiderman, Jacob
AU  - Schneiderman J
AD  - Remodeless CV Ltd., Kiryat-Ono, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230524
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (Leptin)
RN  - 0 (Interleukin-6)
SB  - IM
EIN - Am J Nephrol. 2024 Feb 16;:1. PMID: 38368865
MH  - Animals
MH  - Swine
MH  - Leptin
MH  - Interleukin-6
MH  - Kidney/pathology
MH  - *Reperfusion Injury/drug therapy/prevention & control
MH  - Inflammation/complications
MH  - Ischemia/drug therapy/complications
MH  - Necrosis
MH  - *Acute Kidney Injury/drug therapy/etiology/prevention & control
OTO - NOTNLM
OT  - Inflammation
OT  - Ischemia and reperfusion
OT  - Leptin
OT  - Renal transplantation
EDAT- 2023/05/26 06:42
MHDA- 2023/11/03 06:44
CRDT- 2023/05/26 03:43
PHST- 2023/02/01 00:00 [received]
PHST- 2023/05/13 00:00 [accepted]
PHST- 2023/11/03 06:44 [medline]
PHST- 2023/05/26 06:42 [pubmed]
PHST- 2023/05/26 03:43 [entrez]
AID - 000531174 [pii]
AID - 10.1159/000531174 [doi]
PST - ppublish
SO  - Am J Nephrol. 2023;54(7-8):337-348. doi: 10.1159/000531174. Epub 2023 May 24.