Skip to main content

Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice.

Publication ,  Journal Article
Gu, J; Sun, P; Zhao, H; Watts, HR; Sanders, RD; Terrando, N; Xia, P; Maze, M; Ma, D
Published in: Crit Care
June 24, 2011

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.

Duke Scholars

Published In

Crit Care

DOI

EISSN

1466-609X

Publication Date

June 24, 2011

Volume

15

Issue

3

Start / End Page

R153

Location

England

Related Subject Headings

  • Reperfusion Injury
  • Protective Agents
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Emergency & Critical Care Medicine
  • Dexmedetomidine
  • Cell Line
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gu, J., Sun, P., Zhao, H., Watts, H. R., Sanders, R. D., Terrando, N., … Ma, D. (2011). Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care, 15(3), R153. https://doi.org/10.1186/cc10283
Gu, Jianteng, Pamela Sun, Hailin Zhao, Helena R. Watts, Robert D. Sanders, Niccolo Terrando, Peiyuan Xia, Mervyn Maze, and Daqing Ma. “Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice.Crit Care 15, no. 3 (June 24, 2011): R153. https://doi.org/10.1186/cc10283.
Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, et al. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. 2011 Jun 24;15(3):R153.
Gu, Jianteng, et al. “Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice.Crit Care, vol. 15, no. 3, June 2011, p. R153. Pubmed, doi:10.1186/cc10283.
Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, Xia P, Maze M, Ma D. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. 2011 Jun 24;15(3):R153.

Published In

Crit Care

DOI

EISSN

1466-609X

Publication Date

June 24, 2011

Volume

15

Issue

3

Start / End Page

R153

Location

England

Related Subject Headings

  • Reperfusion Injury
  • Protective Agents
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Emergency & Critical Care Medicine
  • Dexmedetomidine
  • Cell Line
  • Animals