Role of peroxynitrite anion in renal hypothermic preservation injury

Martin J. Mangino, Mary S. Ametani, Barbara J. Gilligan, Csaba Szabo, Lionel Brounts, James H. Southard

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    Background. Peroxynitrite anions may play a role in normothermic renal ischemia and reperfusion. The purpose of this study was to determine if endogenous peroxynitrite anion is involved in renal preservation injury. Methods. Experiments were conducted in isolated canine renal tubules and in a canine autotransplant model of hypothermic preservation injury. Results. Isolated renal tubules demonstrated progressive loss of membrane transport function after reperfusion with increasing cold storage times in UW solution as assessed by tetraethylammonium cation transport (TEA). This transport defect was not altered by reperfusion in the presence of WW85, a peroxynitrite decomposition catalyst. Likewise, tubule LDH release was not altered by WW85. Renal tubules did not demonstrate any evidence of peroxynitrite formation after cold storage (0-120h) or after subsequent reperfusion in vitro as measured by nitrotyrosine adduct formation. Addition of exogenous peroxynitrite (1 mM) directly to freshly isolated renal tubules produced strong nitrotyrosine signals but failed to alter membrane function (TEA uptake). Conversely, SIN-1, a peroxynitrite generator molecule, failed to produce a nitrotyrosine signal in extracted renal tubule proteins but significantly impaired transport function. Finally, function of cold stored canine autografts was not affected by the scavenging of peroxynitrite anions (WW85) before kidney harvest and immediately at reperfusion. Tissue biopsies from cold stored kidney autografts also failed to show evidence of peroxynitrite synthesis either after cold storage (72 h) or after kidney transplantation (60 min reperfusion). Conclusions. This study concludes that peroxynitrite anions are not formed and are not involved in renal preservation injury.

    Original languageEnglish (US)
    Pages (from-to)1455-1460
    Number of pages6
    JournalTransplantation
    Volume80
    Issue number10
    DOIs
    StatePublished - Nov 1 2005

    Keywords

    • Cold ischemia
    • Kidney transplantation
    • Nitric oxide
    • Reactive oxygen species
    • Superoxide

    ASJC Scopus subject areas

    • Transplantation

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  • Cite this

    Mangino, M. J., Ametani, M. S., Gilligan, B. J., Szabo, C., Brounts, L., & Southard, J. H. (2005). Role of peroxynitrite anion in renal hypothermic preservation injury. Transplantation, 80(10), 1455-1460. https://doi.org/10.1097/01.tp.0000181099.20099.d1