Received July 11, 2008
Accepted on October 15, 2008

BASIC RESEARCH

Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1 Activation

Daqing Ma ^*, Ta Lim ^*, Jing Xu , Haidy Tang ^*, Yanjie Wan , Hailin Zhao ^*, Mahmuda Hossain ^*, Patrick H. Maxwell , and Mervyn Maze ^*

*Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Anesthesiology, Gongli Hospital, Pudong, Shanghai, China; and Division of Medicine, Rayne Institute, University College of London, London, United Kingdom

	Abstract

The mortality rate from acute kidney injury after major cardiovascular operations can be as high as 60%, and no therapies have been proved to prevent acute kidney injury in this setting. Here, we show that preconditioning with the anesthetic gas xenon activates hypoxia-inducible factor 1 (HIF-1) and its downstream effectors erythropoietin and vascular endothelial growth factor in a time-dependent manner in the kidneys of adult mice. Xenon increased the efficiency of HIF-1 translation via modulation of the mammalian target of rapamycin pathway. In a model of renal ischemia-reperfusion injury, xenon provided morphologic and functional renoprotection; hydrodynamic injection of HIF-1 small interfering RNA demonstrated that this protection is HIF-1 dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1 and that administration of xenon before renal ischemia can prevent acute renal failure. If these data are confirmed in the clinical setting, then preconditioning with xenon may be beneficial before procedures that temporarily interrupt renal perfusion.