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TAK-242 attenuates renal ischemia and reperfusion injury by inhibiting TLR4 signaling pathway

 
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Research Article  
dx.doi.org/10.18081/2333-5106/015-12/769-779
American Journal of BioMedicine Volume 3, Issue 12, pages 769-779
Received: July 30, 2015; accepted: October 28, 2015; published: December 12, 2015


 Tamas Wilsona, Stefan  A. Wieland, Mark Matsunagaa, ShuJun Zhanga, b mail of corresponding author

Abstract

TAK-242 (resatorvid), a small-molecule–specific inhibitor of Toll-like receptor (TLR) 4 signaling, has been demonstrated to protect renal against IR injury. The aim of this study was to investigate TAK 242 regulates autophagy during IR injury and its possible mechanism. However, the mechanism by which TAK-242 inhibits TLR4 signaling after binding to TLR4 remains unknown. Ischemia-reperfusion induced acute kidney injury (IR-AKI) is used as a model of AKI in mice, unilateral I/R injury followed by contralateral nephrectomy using a dorsal approach, reducing surgical stress resulting from ventral laparotomy. Application of TAK-242 (3 mg/kg IP) was started one day before IRI induction. Both TAK- 242-treated and nontreated mice were sacrificed at several times starting at 30 minutes and finishing on day 7 after IRI induction. The proinflammatory cytokines IL-1β, TNF-α, anti-inflammatory cytokine IL-10 and NF-κB activity were determined in kidneys.

Keywords: TAK-242; TLR4; Renal against IR injury; Proinflammatory cytokines

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

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