Effect of tranilast in comparison with beclomethasone in chronic murine model of asthma

• Published in: Experimental lung research 2016-07, Vol.42 (6), p.296-306
• Main Authors: Nader, Manar A., Gameil, Nariman, Abdelaziz, Rania R., Zalata, Khaled R., Osman, Amal, Zedan, Mohamed M., Abo-Elkheir, Nermin, Elsiddig, Abeer Abdalla, Zedan, Magdy
• Format: Article
• Language: English
• Subjects: Airway Remodeling - drug effects; Animals; Anti-Allergic Agents - pharmacology; Anti-Allergic Agents - therapeutic use; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Asthma - drug therapy; Asthma - immunology; beclomethasone; Beclomethasone - pharmacology; Beclomethasone - therapeutic use; Bronchoalveolar Lavage Fluid - chemistry; chronic asthma; Chronic Disease; Collagen - metabolism; Disease Models, Animal; Drug Evaluation, Preclinical; inflammation; Interleukin-13 - metabolism; Leukocyte Count; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Mice; Nitric Oxide - metabolism; ortho-Aminobenzoates - pharmacology; ortho-Aminobenzoates - therapeutic use; remodeling; tranilast; Transforming Growth Factor beta1 - metabolism
• ISSN: 0190-2148; 1521-0499
• DOI: 10.1080/01902148.2016.1207727

Aim of the Study: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. Materials and Methods: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done. Results: Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation. Conclusions: Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.