Antiinflammatory effects of mercaptoethylguanidine, a combined inhibitor of nitric oxide synthase and peroxynitrite scavenger, in carrageenan-induced models of inflammation

Salvatore Cuzzocrea, Basilia Zingarelli, Paul Hake, Andrew L. Salzman, Csaba Szabo

    Research output: Contribution to journalArticle

    211 Scopus citations

    Abstract

    In vitro studies have demonstrated that mercaptoethylguanidine (MEG), a selective inhibitor of the reducible NO synthase (iNOS) is also effective as a scavenger of peroxynitrite (a potent cytotoxic oxidant produced by the reaction of NO and superoxide). In the present study, we evaluated the antiinflammatory potential of MEG treatment in two models of acute inflammation (carrageenan-induced paw edema and pleurisy), where oxyradicals, NO, and peroxynitrite play a crucial role in the inflammatory process. Our data show that MEG (given at 25 μg/paw in the paw edema model or 10 mg/kg in the pleurisy model) inhibits the inflammatory response (paw swelling, pleural exudate formation, mononuclear cell infiltration, histological injury) in both models. Furthermore, MEG reduced nitrite/nitrite concentrations in the exudate and reduced the activity of the inducible isoform of NO synthase in the lung ex vivo MEG also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. Taken together the present results demonstrate that MEG exerts potent antiinflammatory effects. Part of these antiinflammatory effects may be related to an inhibition of the expression/activity of the inducible NO synthase another part may be related to oxyradical and peroxynitrite scavenging.

    Original languageEnglish (US)
    Pages (from-to)450-459
    Number of pages10
    JournalFree Radical Biology and Medicine
    Volume24
    Issue number3
    DOIs
    StatePublished - Feb 1 1998

    Keywords

    • Carrageenin
    • Free radicals
    • Inflammation
    • NO synthase
    • Nitric oxide
    • Peroxynitrite
    • Prostaglandins
    • Shock
    • Superoxide

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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