title: Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.
abstract: Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.
authors.affiliation: 1Department of Surgery and Cancer, Section of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK. d.ma@imperial.ac.uk.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhao
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Rele
authors.initials: R
authors.lastname: Ologunde
authors.forename: Kieran P
authors.initials: KP
authors.lastname: O'Dea
authors.forename: Masao
authors.initials: M
authors.lastname: Takata
authors.forename: Catherine
authors.initials: C
authors.lastname: Tralau-Stewart
authors.forename: Andrew J T
authors.initials: AJ
authors.lastname: George
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D003080:Cold Temperature / Q000009:adverse effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D005802:Genes, MHC Class II; D018840:HSP70 Heat-Shock Proteins; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D016328:NF-kappa B; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013048:Specimen Handling; D014978:Xenon / Q000494:pharmacology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D014978:Xenon; D016572:Cyclosporine; D051547:Heme Oxygenase-1
keywords: acute rejection; renoprotection