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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs

Ylenia Suzuki, Emanuela Masini, Cosimo Mazzocca, Salvatore Cuzzocrea, Anna Ciampa, Hisanori Suzuki and Daniele Bani
Journal of Pharmacology and Experimental Therapeutics December 2004, 311 (3) 1241-1248; DOI: https://doi.org/10.1124/jpet.104.072546
Ylenia Suzuki
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Emanuela Masini
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Cosimo Mazzocca
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Salvatore Cuzzocrea
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Anna Ciampa
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Hisanori Suzuki
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Daniele Bani
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Abstract

Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergen-induced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-α in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.

Footnotes

  • This study was supported by a grant from the Italian Ministry of Education, University and Research (MIUR, PRIN 2002 to H.S. and D.B.) and by funds from the Universities of Verona and Florence.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.104.072546.

  • ABBREVIATIONS: PARP, poly(ADP-ribose) polymerase; NO, nitric oxide; PBS, phosphate-buffered saline; ANOVA, analysis of variance; TNF, tumor necrosis factor.

    • Received June 10, 2004.
    • Accepted July 9, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 311 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 3
1 Dec 2004
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs

Ylenia Suzuki, Emanuela Masini, Cosimo Mazzocca, Salvatore Cuzzocrea, Anna Ciampa, Hisanori Suzuki and Daniele Bani
Journal of Pharmacology and Experimental Therapeutics December 1, 2004, 311 (3) 1241-1248; DOI: https://doi.org/10.1124/jpet.104.072546

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs

Ylenia Suzuki, Emanuela Masini, Cosimo Mazzocca, Salvatore Cuzzocrea, Anna Ciampa, Hisanori Suzuki and Daniele Bani
Journal of Pharmacology and Experimental Therapeutics December 1, 2004, 311 (3) 1241-1248; DOI: https://doi.org/10.1124/jpet.104.072546
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