Erdosteine effects cell barriers causing decreased inflammation and increased pulmonary function in asthmatic mice exposed to nanoparticulate pollution

Abstract

Objectives: Erdosteine, an oral mucoactive anti-oxidant molecule, interferes with the pathological processes seen in respiratory disorders including thickened or increased mucus production, increased oxidative stress, and chronic inflammation; however, its efficacy as an asthma therapy remains to be fully clarified. Therefore, the aim of this study was to assess the effects of erdosteine on epithelial barrier function in asthma. Methods: To investigate the effects of erdosteine on cell barrier expression in a mouse model of asthma, BALB/c mice ( n = 8 per group; total of 40 mice) were exposed to saline (Sham), ovalbumin (OVA), or OVA plus TiO 2 inhalation (200 μg/m 3 ; OVA + TiO 2 ). The mice were then treated with erdosteine orally (OVA + TiO 2 + Erdos) or intraperitoneal dexamethasone (OVA + TiO 2 + Dex). Bronchoalveolar lavage and histology were performed. Enhanced pause was used as an indicator of pulmonary function, and samples were collected. The effect of erdosteine on cell barrier expression was assessed by immunoblotting and immunohistochemical analyses. Results: OVA + TiO 2 + erdosteine mice exhibited decreased inflammation, and mucous gland hyperplasia, and increased pulmonary function compared with OVA + TiO 2 mice. Levels of claudin (CLDN)-4 and nectin-4 protein were higher in lung tissue from OVA + TiO 2 mice than Sham and OVA mice, and were reduced by erdosteine treatment. In contrast, CLDN14 and CLDN18 protein levels were lower in lung tissue from OVA + TiO 2 mice than those from control mice, but were increased by treatment with erdosteine. Conclusion: Cell barriers are involved in airway inflammation in asthma patients, and erdosteine reduces airway inflammation by changing the cell barrier.