Impact of the MuRF-1 inhibitor Myomed-205 on the diaphragm of mice exposed to tobacco smoke

• Grant number: 22/14464-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Anselmo Sigari Moriscot
• Grantee: Luis Antonio Chinait Hess Costa Dutra
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pulmonary emphysema is a chronic and progressive inflammatory disease that causes dyspnea, exercise capacity limitation, sarcopenia and weight loss that affects 17% of the population in Brazil and 10% of the adult population in industrialized countries. The present study aims to evaluate the effect of a selective inhibitor of MuRF1 activity (Muscle-RING Finger Protein 1), the compound MyoMed-205. Our hypothesis contemplates that this compound will be able to protect the mass and function of the diaphragm, in a model of exposure to tobacco smoke with evolution to pulmonary emphysema.Therefore, male C57BL/6 mice will be randomized into 5 groups: Control (CON), exposed to cigarette smoke (CS), CS that received the compound (CS 205), CS 205 that followed the exercise protocol (CS 205 EX ) and CS who followed the exercise protocol without receiving the compound (CS Ex). The MyoMed-205 compound will be added to the diet at the beginning of the emphysema induction protocol until the final evaluation at 90 days. Pulmonary emphysema will be induced by inhaling tobacco smoke (cigarette) in a chamber for 30 minutes, twice a day, 5 days a week, for 90 days. The animals will also be submitted to a standardized physical training program consisting of 05 weekly sessions of 60 minutes, for 90 days. The animals will be submitted to the evaluation of the cross-sectional area (CSA) of the muscle fibers of the diaphragm. In addition, a qualitative analysis will be performed using HE staining and depending on the results, additional stains. This project has the potential to contribute to possible future therapeutic strategies, aiming to spare the diaphragm muscle in cases involving chronic obstructive pulmonary diseases.