Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation.
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 1alpha (HIF-1alpha) 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-1alpha 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-1alpha small interfering RNA demonstrated that this protection is HIF-1alpha dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1alpha 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.
Ma
Daqing
D
Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea & Westminster Campus, 369 Fulham Road, London SW10 9NH, United Kingdom. d.ma@imperial.ac.uk
Lim
Ta
T
Xu
Jing
J
Tang
Haidy
H
Wan
Yanjie
Y
Zhao
Hailin
H
Hossain
Mahmuda
M
Maxwell
Patrick H
PH
Maze
Mervyn
M
D000777:Anesthetics / Q000008:administration & dosage; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D004921:Erythropoietin / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014978:Xenon / Q000008:administration & dosage / Q000627:therapeutic use*; D000099162:Endothelial PAS Domain-Containing Protein 1
D000777:Anesthetics; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004921:Erythropoietin; D017853:Phosphotransferases (Alcohol Group Acceptor); D021122:Protein Subunits; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; D025801:Ubiquitin; D042461:Vascular Endothelial Growth Factor A; D014978:Xenon; D000099162:Endothelial PAS Domain-Containing Protein 1; C546842:MTOR protein, human; C546843:mTOR protein, mouse