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Critical Care
Published in: Critical Care 3/2011

Open Access 01-06-2011 | Research

Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice

Authors: Jianteng Gu, Pamela Sun, Hailin Zhao, Helena R Watts, Robert D Sanders, Niccolo Terrando, Peiyuan Xia, Mervyn Maze, Daqing Ma

Published in: Critical Care | Issue 3/2011

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Abstract

Introduction

Acute kidney injury following surgery incurs significant mortality with no proven preventative therapy. We investigated whether the α2 adrenoceptor agonist dexmedetomidine (Dex) provides protection against ischemia-reperfusion induced kidney injury in vitro and in vivo.

Methods

In vitro, a stabilised cell line of human kidney proximal tubular cells (HK2) was exposed to culture medium deprived of oxygen and glucose. Dex decreased HK2 cell death in a dose-dependent manner, an effect attenuated by the α2 adrenoceptor antagonist atipamezole, and likely transduced by phosphatidylinositol 3-kinase (PI3K-Akt) signaling. In vivo C57BL/6J mice received Dex (25 μg/kg, intraperitoneal (i.p.)) 30 minutes before or after either bilateral renal pedicle clamping for 25 minutes or right renal pedicle clamping for 40 minutes and left nephrectomy.

Results

Pre- or post-treatment with Dex provided cytoprotection, improved tubular architecture and function following renal ischemia. Consistent with this cytoprotection, dexmedetomidine reduced plasma high-mobility group protein B1 (HMGB-1) elevation when given prior to or after kidney ischemia-reperfusion; pretreatment also decreased toll-like receptor 4 (TLR4) expression in tubular cells. Dex treatment provided long-term functional renoprotection, and even increased survival following nephrectomy.

Conclusions

Our data suggest that Dex likely activates cell survival signal pAKT via α2 adrenoceptors to reduce cell death and HMGB1 release and subsequently inhibits TLR4 signaling to provide reno-protection.
Appendix
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Metadata
Title
Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice
Authors
Jianteng Gu
Pamela Sun
Hailin Zhao
Helena R Watts
Robert D Sanders
Niccolo Terrando
Peiyuan Xia
Mervyn Maze
Daqing Ma
Publication date
01-06-2011
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2011
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc10283

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