Protective effects of 3-aminobenzamide, an inhibitor of poly (ADP- ribose) synthase in a carrageenan-induced model of local inflammation

Salvatore Cuzzocrea, Basilia Zingarelli, Eli Gilad, Paul Hake, Andrew L. Salzman, Csaba Szabó

    Research output: Contribution to journalArticle

    88 Scopus citations

    Abstract

    A cytotoxic cycle triggered by oxidant-induced DNA single strand breakage and subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase have been shown to contribute to the cellular injury during various forms of oxidant stress in vitro. The aim of the present study was to investigate the role of poly (ADP-ribose) synthetase in a model of acute local inflammation (carrageenan-induced pleurisy), where oxyradicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The results show that the poly (ADP-ribose) synthetase inhibitor 3- aminobenzamide (given at 1-30 mg/kg) inhibits the inflammatory response (pleural exudate formation, mononuclear cell infiltration, histological injury). Moreover, 3-aminobenzamide reduces the formation of nitrotyrosine, an indicator of the formation of peroxynitrite, in the lung. The present results demonstrate that 3-aminobenzamide, presumably by inhibition of poly (ADP-ribose) synthetase, exerts potent anti-inflammatory effects. Part of the anti-inflammatory effects of 3-aminobenzamide may be related to a reduction of neutrophil recruitment into the inflammatory site.

    Original languageEnglish (US)
    Pages (from-to)67-76
    Number of pages10
    JournalEuropean Journal of Pharmacology
    Volume342
    Issue number1
    DOIs
    StatePublished - Jan 19 1998

    Keywords

    • Apoptosis
    • DNA strand break
    • Neutrophil
    • Nitric oxide (NO)(i)
    • Peroxynitrite

    ASJC Scopus subject areas

    • Pharmacology

    Fingerprint Dive into the research topics of 'Protective effects of 3-aminobenzamide, an inhibitor of poly (ADP- ribose) synthase in a carrageenan-induced model of local inflammation'. Together they form a unique fingerprint.

  • Cite this