Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways

Hussam AS Murad^1,2 , Hamed S Habib³, Misbahuddin M Rafeeq¹, Mansour I Sulaiman⁴, Amer S Abdulrahman⁵, Mohamad-Nidal A Khabaz⁵

¹Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia; ²Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; ³Department of Pediatrics; ⁴Department of Pharmacology; ⁵Department of Pathology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.

For correspondence:- Hussam Murad Email: hamurad@kau.edu.sa Tel:+966541541341

Accepted: 26 October 2017 Published: 30 November 2017

Citation: Murad HA, Habib HS, Rafeeq MM, Sulaiman MI, Abdulrahman AS, Khabaz MA. Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways. Trop J Pharm Res 2017; 16(11):2637-2644 doi: 10.4314/tjpr.v16i11.10

© 2017 The authors.
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Abstract

Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice.

Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated groups. The following treatments were given by inhalation (15 min once/day) for seven days: roflumilast (500 µg/kg), formoterol (50 µg/kg), fluticasone (1000 µg/kg), roflumilast + fluticasone (500 + 1000 µg/kg), and formoterol + fluticasone (50 + 1000 µg/kg). Ultrathin lung sections (50 - 70 nm thick) were examined by transmission electron microscopy.

Results: The asthmatic mice showed marked degenerative changes in bronchiolar epithelial cells. The alveolar septal walls were thickened with cellular changes and capillary congestion. The basement membranes showed marked thickening and the airway lumens contained abundant mucinous secretions. These ovalbumin-induced ultrastructural airway changes were markedly-reversed in the roflumilast + fluticasone group, moderately-reversed in the roflumilast, fluticasone, and formoterol + fluticasone groups, but were not affected in the formoterol group.

Conclusion: Co-inhalation of roflumilast + fluticasone significantly improved the ultrastructural airway changes than co-inhalation of formoterol + fluticasone in ovalbumin-asthmatic mice due to its anti-inflammatory and antifibrotic effects.

Keywords: Asthma, Fluticasone Propionate, Formoterol, Roflumilast, Ovalbumin, Remodeling, Bronchiolar epithelium