Effect of hydrogen sulphide (H2S) on pulmonary remodeling in mice asthma

• Grant number: 18/15995-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2018
• End date: October 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Heloisa Helena de Araujo Ferreira
• Grantee: Heloisa Helena de Araujo Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Asthma is a chronic inflammatory disease resulting from structural changes in the airways in response to mediators released in the acute phase of the immediate hypersensitivity reaction. Repeated lesions, repair and regeneration of the airway epithelium after exposure to allergens and environmental factors result in histological changes and functional mucosal abnormalities that contribute to the pathophysiology of asthma, clinically characterized by intermittent and reversible airway obstruction, chronic bronchial inflammation , bronchial smooth muscle cell hypertrophy and hyperreactivity to bronchoconstrictors. Besides the influence on the maintenance of the inflammatory cellular component in the allergic response, consisting by eosinophils, neutrophils, lymphocytes and mast cells, cytokines such as TNF-±, VEGF, TGF-², IL-25 and IL-13 are related to the indicators of remodeling of the lung tissue associated with asthma, such as the proliferation of epithelial cells with goblet cell hyperplasia, increased mucus secretion, smooth muscle hyperplasia and hypertrophy, subepithelial fibrosis and increased vascularization. Using an experimental model of asthma in mice, we will verify in this research project whether treatment with an H2S donor, sodium hydrosulfide (NaHS), is able to prevent structural changes in lung tissue characteristic of asthma. It will also be verified whether soluble guanylate cyclase is the target of H2S action in asthma. The effects of the treatment of asthmatic mice with NaHS on the following pulmonary parameters will be investigated: 1) hyperreactivity and remodeling; 2) angiogenesis and lymphogenesis; 3) levels of cytokines related to remodeling; 4) expression of the enzymes CBS, CSE and MST; 5) cGMP levels. (AU)