An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice

Wilma L. Suarez-Pinzon, Jon G. Mabley, Ken Strynadka, Robert F. Power, Csaba Szabó, Alex Rabinovitch

    Research output: Contribution to journalArticle

    86 Scopus citations

    Abstract

    Peroxynitrite (ONOO-) is a highly reactive oxidant produced by the interaction of the free radicals superoxide (O2·-) and nitric oxide (NO·). In a previous study, we found that peroxynitrite is formed in islet β-cells of nonobese diabetic (NOD) mice. Here, we report that guanidinoethyldisulphide (GED), a selective inhibitor of inducible nitric oxide synthase (iNOS) and scavenger of peroxynitrite prevents diabetes in NOD mice. GED treatment of female NOD mice, starting at age 5 weeks, delayed diabetes onset (from age 12 to 22 weeks) and significantly decreased diabetes incidence at 30 weeks (from 80% to 17%). GED did not prevent pancreatic islet infiltration by leukocytes; however, β-cells that stained positive for nitrotyrosine (a marker of peroxynitrite) were significantly decreased in islets of GED-treated mice (1±1%) compared with vehicle-treated mice (30±9%). In addition, GED significantly inhibited nitric oxide and nitrotyrosine formation and decreased destruction of β-cells in NOD mouse islets incubated in vitro with the combination of proinflammatory cytokines interleukin 1-beta (IL-1β), tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). These findings indicate that both superoxide and nitric oxide radicals contribute to islet β-cell destruction in autoimmune diabetes via peroxynitrite formation in the β-cells.

    Original languageEnglish (US)
    Pages (from-to)449-455
    Number of pages7
    JournalJournal of Autoimmunity
    Volume16
    Issue number4
    DOIs
    StatePublished - Jul 7 2001

    Keywords

    • Free radicals
    • Insulitis
    • NOD mice
    • Nitric oxide
    • Peroxynitrite

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Fingerprint Dive into the research topics of 'An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice'. Together they form a unique fingerprint.

  • Cite this

    Suarez-Pinzon, W. L., Mabley, J. G., Strynadka, K., Power, R. F., Szabó, C., & Rabinovitch, A. (2001). An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice. Journal of Autoimmunity, 16(4), 449-455. https://doi.org/10.1006/jaut.2001.0507