Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Ozone exposure induces cough hypersensitivity in mice

Tinglei Li, Shu Zhang, Xuemei Liu, Tianyuan Xin, Yu Chen, Zhe Chen

Laboratory of Cough, Affiliated Kunshan Hospital of Jiangsu University, 215300 Jiangsu, China;

For correspondence:- Zhe Chen Email: z.chen@vip.163.com

Accepted: 5 October 2023 Published: 31 October 2023

Citation: Li T, Zhang S, Liu X, Xin T, Chen Y, Chen Z. Ozone exposure induces cough hypersensitivity in mice. Trop J Pharm Res 2023; 22(10):2127-2134 doi: 10.4314/tjpr.v22i10.14

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To study the influence of O₃ exposure on cough sensitivity, airway barrier function and airway inflammation in mice.

Methods: Cough sensitivity was determined in healthy male C57/BL6 mice (aged 8 - 10 weeks) which were exposed to different concentrations of O₃ (0.5 - 2 ppm) for 3 h daily for 9 days. Hematoxylin and eosin (H&E) staining of lung tissues, collection of BALF, and cell count were carried out. Inflammatory factor levels in pulmonary tissues were determined by enzyme-linked immunosorbent assay (ELISA), while Western blotting was used to assay TRPA1 and Claudin-1 protein expressions in lung tissues.

Results: After 9 days of mice exposure to O₃, cough sensitivity increased significantly, and TRPA1 protein was increased in pulmonary tissues, with exposure level of 1 ppm resulting in the highest level of TRPA1 protein expression. Claudin-1 expression in lung tissues of mice decreased after O₃ exposure, especially in the groups exposed to O₃ levels of 0.5 ppm and 2 ppm. The total cell count in alveolar lavage fluid of mice exposed to O₃ was significantly increased (p < 0.05). In addition, O₃ exposure increased IL-1α, IL-6 and TNF-α levels, with the most significant increase in the 0.5 ppm group (p < 0.05). Results from histology revealed that all mice had inflammatory reactions and destruction of lung tissues after O₃ exposure.

Conclusion: Exposure to O₃ induces disruption of airway barrier function, infiltration of the airway by inflammatory cells, and increased secretion of inflammatory factors, thereby resulting in enhanced cough sensitivity.

Keywords: Ozone, Cough hypersensitivity, Inflammatory cells, Airway barrier, Cytokines