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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on July 13, 2004; DOI: 10.1124/jpet.104.072546

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Received for publication June 10, 2004.
Revised July 9, 2004.
Accepted for publication July 9, 2004.

INHIBITION OF POLY(ADP-RIBOSE) POLYMERASE PREVENTS ALLERGEN-INDUCED ASTHMA-LIKE REACTION IN SENSITISED GUINEA PIGS

Ylenia Suzuki 1, Emanuela Masini 2, Cosimo Mazzocca 2, Salvatore Cuzzocrea 3, Anna Ciampa 4, Hisanori Suzuki 4, Daniele Bani 5*

1 Department of Pediatrics, University of Verona, Italy 2 Department of Preclinical and Clinical Pharmacology, University of Florence, Italy 3 Institute of Pharmacology, University of Messina, Italy 4 Department of Neuroscience and Vision, University of Verona, Italy 5 Department of Anatomy, Histology and Forensic Medicine, University of Firenze, Italy

* Address correspondence to: E-mail: daniele.bani{at}unifi.it

Abstract

Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Asthma being 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-sensitised guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, while they became severe in the sensitised 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 TNF-{alpha}; in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.w.) or 5-aminoisoquinolinone (0.5 mg/kg b.w.) given i.p. 3 hours 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 analogue of 3-aminobenzamide, had no effects.


Key words: 3-aminobenzamide, 5-aminoisoquinolinone, PARP, asthma-like reaction, guinea pig, ovalbumin


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