EVALUATION OF AUTOPHAGY IN A MURINE MODEL OF ASTHMA-CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) OVERLAP SYNDROME AFTER TREATMENT WITH OUABAIN

• Grant number: 24/06058-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Martina Raissa Ribeiro
• Supervisor: Javier Ruben Caso Fernandez
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Universidad Complutense de Madrid (UCM), Spain
• Associated to the scholarship: 21/12906-0 - Evaluation of ouabain modulator function in central and peripheral inflammation in mixed asthma murine model., BP.DR

Abstract

Asthma is a chronic inflammatory disease of the airwaysthathasnocure.Asaresult of constant inflammation, the airways undergo a remodeling process, with reduced airflow, increased mucus, hyperplasia and hypertrophy of the smooth muscles of the airway. Its treatmentconsistsmainlyofbronchodilatorsandinhaledglucocorticoids. However, approximately 20% of theasthmaticpopulationhasrespiratoryoverlapthat causes worsening of symptoms. This syndrome is caused by another inflammatory disease, called'chronicobstructivepulmonarydisease'(COPD). COPD is a disease characterized by causing shortness of breath, wheezing, a large increase in phlegm production, and tiredness. It is another serious respiratory disease with a high annual mortality rate. In 2014, the term asthma-COPD overlaporACOwasestablished by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) and Global InitiativeforAsthma(GINA)committees. Evidence in the literature indicates disorders in the central nervous system (CNS) associated with peripheral inflammation. Asthma and COPD separately have the capacity to increase circulating inflammatory cytokines. Furthermore, they can significantly alter the body's homeostasis. In this project we will study the inflammatory and metabolic mechanismsassociatedwiththemurinemodelofasthma-COPDoverlap(ACO). In addition, we will undergo treatment with the substance Ouabain, which is a cardiotonic glycoside capable of modulating some inflammatory pathways. Instudiesbyour group, promising effects of the substance ouabain were observed in reducing cells in the bronchoalveolar lavageofanimalssubjectedtoallergiclunginflammation,decreasingairway reactivity, as well as protecting the CNS from peripheral inflammation caused by lipopolysaccharide(LPS). It is important to highlight that the involvementofautophagyandneuroinflammation in an ACO model was not found in the literature, nor was the study of the involvement of ouabain.