Evaluation of the therapeutic effects of melatonin on bronchial hyperresponsiveness, airway inflammation and remodeling, in experimental models of asthma, COPD and in the association asthma and COPD: comparison with the use of corticosteroid

Abstract

Asthma and Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence in society, and their pathophysiology are associated with increased pulmonary inflammation, which also occurs in the overlapping of Asthma and COPD (ACO). Furthermore, melatonin showed modulatory activity in inflammation and oxidative stress. Therefore, melatonin is a possible therapeutic target in the treatment of pulmonary inflammatory diseases. Objectives: To evaluate the therapeutic effect of melatonin on bronchial hyperresponsiveness, airway inflammation and remodeling, in experimental models of asthma, COPD and ACO compared to the treatment with dexamethasone. Methods: The study was approved by the Ethics Committee on the Use of Animals of the Faculdade de Medicina da Universidade de São Paulo (n.1430/20). One hundred and twenty-eight Balb/c mice (male, 25-30g, 6-7 weeks old) will be divided into 8 groups. They will be sensitized with ovalbumin for an experimental model of chronic allergic pulmonary inflammation, with elastase for an experimental model of emphysema and sensitized with ovalbumin and elastase for ACO model (n = 8 per group). The treatment groups will receive 15mg/kg melatonin o5r 5mg/kg of dexamethasone, intraperitoneally, and the control groups will receive only saline solution. After the experimental protocol period of 28 days, we will evaluate exhaled nitric oxide, respiratory system mechanics and bronchoalveolar lavage fluid. After this evaluation, the lungs will be removed in monobloc with the heart and embedded in paraffin for morphological and histopathological analysis of the pulmonary tissue. Also, evaluation of Gene Expression of IL-4, IL-5, IL6, IL-13, IL-17, IL1-Beta and TNF-Alpha will be performed by RT-PCR. (AU)