title: Hydrogen Sulfide Protects Renal Grafts Against Prolonged Cold Ischemia-Reperfusion Injury via Specific Mitochondrial Actions.
abstract: Ischemia-reperfusion injury is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement, and prolonged ischemia-reperfusion injury IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury. Donor allografts from Brown Norway rats treated with University of Wisconsin (UW) solution + H2S (150 μM NaSH) during prolonged (24-h) cold (4°C) storage exhibited significantly (p < 0.05) decreased acute necrotic/apoptotic injury and significantly (p < 0.05) improved function and recipient Lewis rat survival compared to UW solution alone. Treatment of rat kidney epithelial cells (NRK-52E) with the mitochondrial-targeted H2S donor, AP39, during in vitro cold hypoxic injury improved the protective capacity of H2S >1000-fold compared to similar levels of the nonspecific H2S donor, GYY4137 and also improved syngraft function and survival following prolonged cold storage compared to UW solution. H2S treatment mitigates cold IRI-associated renal injury via mitochondrial actions and could represent a novel therapeutic strategy to minimize the detrimental clinical outcomes of prolonged cold IRI during RTx.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.|Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Lobb
authors.affiliation: Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Lian
authors.affiliation: Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Haig
authors.affiliation: Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: M N
authors.initials: MN
authors.lastname: Saha
authors.affiliation: University of Exeter Medical School, Exeter, UK.
authors.forename: R
authors.initials: R
authors.lastname: Torregrossa
authors.affiliation: Department of Biosciences, College of Life and Environmental Sciences, Exeter, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Wood
authors.affiliation: University of Exeter Medical School, Exeter, UK.
authors.forename: M
authors.initials: M
authors.lastname: Whiteman
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.|Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre, London, Ontario, Canada.|Department of Surgery, University of Western Ontario, London, Ontario, Canada.|Multi-Organ Transplant Program, London Health Sciences Center, London, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Sener
mesh_terms: D000818:Animals; D050377:Cold Ischemia; D064426:Gasotransmitters / Q000008:administration & dosage; D006085:Graft Survival; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007668:Kidney / Q000098:blood supply; D016030:Kidney Transplantation; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014184:Transplantation, Homologous
chemical_list: D064426:Gasotransmitters; D006862:Hydrogen Sulfide
keywords: animal models: murine; basic (laboratory) research/science; cell death; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; organ perfusion and preservation; translational research/science