Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice.

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.

• Authors: Jianteng Gu, Pamela Sun, Hailin Zhao, Helena R Watts, Robert D Sanders, Niccolo Terrando, Peiyuan Xia, Mervyn Maze, Daqing Ma
• Journal: Critical care (London, England) (Crit Care) Vol. 15 Issue 3 Pg. R153 (Jun 24 2011) ISSN: 1466-609X [Electronic] England
• PMID: 21702944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protective Agents
• Dexmedetomidine

Topics

• Acute Kidney Injury (metabolism, pathology, prevention & control)
• Animals
• Cell Line
• Dexmedetomidine (therapeutic use)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Protective Agents (therapeutic use)
• Reperfusion Injury (metabolism, pathology, prevention & control)