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Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice

Jianteng Gu12, Pamela Sun1, Hailin Zhao1, Helena R Watts1, Robert D Sanders1, Niccolo Terrando3, Peiyuan Xia2*, Mervyn Maze3 and Daqing Ma14*

Author Affiliations

1 Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Rd, London SW10 9NH, UK

2 Department of Pharmacy, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, China

3 Department of Anesthesia and Perioperative Care, UCSF, 521 Parnassus Avenue, San Francisco, CA 94143, USA

4 Department of Anesthesiology, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China

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Critical Care 2011, 15:R153  doi:10.1186/cc10283

Published: 24 June 2011



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.


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.


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.


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.