Evaluation of ouabain modulator function in central and peripheral inflammation in mixed asthma murine model.

• Grant number: 21/12906-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Martina Raissa Ribeiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system, AP.TEM
• Associated scholarship(s): 24/06058-5 - EVALUATION OF AUTOPHAGY IN A MURINE MODEL OF ASTHMA-CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) OVERLAP SYNDROME AFTER TREATMENT WITH OUABAIN, BE.EP.DR

Abstract

Ouabain is classically known as an endogenous cardiotonic steroid that inhibits Na+/K+-ATPase. Despite knowledge of its synthesis by the adrenals, pituitary and hypothalamus, the physiological role of ouabain has not been fully elucidated. Researchers involved in this proposal have demonstrated that ouabain has anti-inflammatory effects on the immune system and the central nervous system, being able to modulate several signaling pathways. Within this context, it was also described that ouabain has an anti-inflammatory action in a model of acute allergic inflammation induced by hypersensitivity to ovalbumin.However, there are no data in the literature on the effect of ouabain on the chronic asthma process. Asthma is a chronic inflammatory disease that involves the participation of immune system and nervous system cells and, in association with epithelial cells, leads to bronchial hyperreactivity, increased mucus production and remodeling of the lower airways. In Brazil, the prevalence in the diagnosis of asthma is approximately 12%, which is higher than the global prevalence among developing countries. In 2017, according to DATASUS, the asthma mortality rate in Brazil was more than 2100 cases, of which almost 30% were in the northeast region, with 46 cases in the state of Paraíba, and about 42% in the southeast region, with approximately 360 cases in the state of São Paulo.In addition, asthma hospitalization costs exceed more than 20 million dollars in these two regions, totaling more than 65% of these expenses in the country. Therefore, this work aims to elucidate the effect of treatment with ouabain in the murine asthma model. In this model, inflammatory parameters in the immune system and nervous system will be evaluated, including cytokines and different signaling pathways involved in asthma, as well as biochemical and molecular biology assays associated with this study. Thus, we intend to contribute to the studies of the effect of ouabain on the peripheral and central inflammatory process, in addition to evaluating the changes induced by this molecule in the asthmatic process, specifically on pulmonary mechanics and airway reactivity. Therefore, this proposal is comprehensive, as it not only involves the development of a relevant research project, but also involves the training of human resources in a new area that presents a great perspective of technological development aimed at the therapy of diseases associated with the CNS and inflammation.