PT - JOURNAL ARTICLE AU - Ylenia Suzuki AU - Emanuela Masini AU - Cosimo Mazzocca AU - Salvatore Cuzzocrea AU - Anna Ciampa AU - Hisanori Suzuki AU - Daniele Bani TI - Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs AID - 10.1124/jpet.104.072546 DP - 2004 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1241--1248 VI - 311 IP - 3 4099 - http://jpet.aspetjournals.org/content/311/3/1241.short 4100 - http://jpet.aspetjournals.org/content/311/3/1241.full SO - J Pharmacol Exp Ther2004 Dec 01; 311 AB - 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. The American Society for Pharmacology and Experimental Therapeutics