Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like reaction in sensitized Guinea pigs.
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-alpha 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.
Suzuki
Ylenia
Y
Department of Anatomy, Histology, and Forensic Medicine, Section of Histology, University of Florence, Viale G. Pieraccini, 6, I-50139 Florence, Italy.
Masini
Emanuela
E
Mazzocca
Cosimo
C
Cuzzocrea
Salvatore
S
Ciampa
Anna
A
Suzuki
Hisanori
H
Bani
Daniele
D
D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents; D001249:Asthma / Q000503:physiopathology / Q000517:prevention & control*; D001549:Benzamides / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
C411425:5-aminoisoquinolinone; D000485:Allergens; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C025160:3-aminobenzamide; D010047:Ovalbumin; D009195:Peroxidase