Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gu, J; Sun, P; Zhao, H; Watts, HR; Sanders, RD; Terrando, N; Xia, P; Maze, M; Ma, D

Published Date

  • June 24, 2011

Published In

Volume / Issue

  • 15 / 3

Start / End Page

  • R153 -

PubMed ID

  • 21702944

Pubmed Central ID

  • 21702944

Electronic International Standard Serial Number (EISSN)

  • 1466-609X

Digital Object Identifier (DOI)

  • 10.1186/cc10283

Language

  • eng

Conference Location

  • England