02 May 2003
Prevention of antigen-induced bronchoconstriction by of poly(ADP-ribose)polymerase inhibitors in actively sensitized guinea pigs
E. Masini, Y. Suzuki, S. Pierpaoli, S. Cuzzocrea, D. Bani, H. SuzukiMed Sci Monit 2003; 9(1): 40-0 :: ID: 15103
Abstract
Poly(ADP-ribose) polymerase-1(PARP-1), plays an important role in the tissue injury in conditions associated with oxidative stress and inflammation. Oxidative and nitrosative stress can trigger DNA strand breakage, and activates the nuclear enzyme PARP-1. Since free radicals are involved in the pathogenesis of asthma [1], we aimed at evaluating the effects of the inhibition of PARP-1 activity on the antigen-induced bronchospasm in a model of allergic asthma in sensitized guinea pigs. Male albino guinea pigs sensitized with ovalbumin (OVA), were placed in whole body respiratory chambers and challenged with OVA. 3 aminobenzamide (3AB, 1 g/kg b.w.) or 5 aminoisoquinolinone (5-AIQ, 0.5 mg/kg b. w.) were given i.p. 3 hours before OVA challenge or by aerosol (10 mg/ml or 0.5 mg/ml respectively) 30 min before OVA challenge.The following parameters were recorded: latency time in bronchocostriction; cough severity score and onset of respiratory failure. The spasm latency in response to OVA aerosol is rather high in naive animals, while it decreases sharply in sensitised animals. Treatment with 3AB or with 5-AIQ, i.p or per aerosol, significantly reduced severity of cough and delayed appearance of bronchial spasm and respiratory failure. Furthermore, both compounds were able to prevent bronchiolar constriction and pulmonary air space inflation and to decrease myeloperoxidase activity and mast cell degranulation in lung tissue. These findings provide the first evidence that the PARP-1 inhibitors can counteract neutrophil- and mast cell-mediated acute allergic bronchospasm in actively sensitized guinea pigs and suggest a possible future use of these drugs in asthma. References: 1.Barnes PJ: Reactive oxygen species and airway inflammation. Free Radic Biol Med, 1990; 9: 235-243
Keywords: PARP-1, 3-aminobenzamide, 5-aminoisoquinolinone, allergic bronchospasm, guinea pig
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
06 Mar 2024 : Clinical Research
Prevalence and Variation of Medical Comorbidities in Oral Surgery Patients: A Retrospective Study at Jazan ...Med Sci Monit In Press; DOI: 10.12659/MSM.943884
08 Mar 2024 : Clinical Research
Evaluation of Foot Structure in Preschool Children Based on Body MassMed Sci Monit In Press; DOI: 10.12659/MSM.943765
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952