The antioxidant role of aerobic physical exercise in experimental models of chronic allergic inflammation and pulmonary infection by Streptococcus pneumoniae

• Grant number: 18/19966-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2019
• End date: April 30, 2021
• Field of knowledge: Health Sciences - Physiotherapy and Occupational Therapy
• Principal Investigator: Clarice Rosa Olivo
• Grantee: Clarice Rosa Olivo
• Host Institution: Pró-Reitoria de Pós-Graduação, Pesquisa e Extensão. Universidade Cidade de São Paulo (UNICID). São Paulo , SP, Brazil
• Associated researchers: Beatriz Mangueira Saraiva ; Carla Máximo Prado ; Iolanda de Fátima Lopes Calvo Tibério ; Maria Isabel Cardoso Alonso-Vale ; Viviani Barnabé

Abstract

Object of several experimental and clinical studies, continuous aerobic physical exercise has gained prominence due to its important role in the combat and / or treatment of some chronic diseases. Although there is some work already suggesting that it may play an anti-inflammatory role, especially in lung diseases, the mechanisms by which this happens are still not fully understood and many people are still reluctant to carry them out. At the same time, it is known that Nrf2 (factor 2 erythroid nuclear factor 2), a transcription factor with an important role in the regulation of the host's antioxidant defense, has already been pointed out as one of the possible defense mechanisms in infection with S. pneumonia and asthma, and seems to be involved in the anti-inflammatory mechanisms of aerobic exercise. Briefly, at baseline, Nrf2 is bound to KEAP1 (kelch-like ECH-associated protein 1) in the cytoplasm of cells, promoting its ubiquitination and degradation. In the presence of reactive oxygen species (ROS), KEAP1 is inactivated, releasing Nrf2 to translocate to the nucleus and activate genes encoding antioxidant proteins, such as superoxide desmutase (SOD) and glutathione peroxidase (GSH). In addition, Nrf2 appears to inhibit the expression of pro-inflammatory mediators by regulating anti-inflammatory enzymes such as heme oxygenase-1 (HO-1). At the same time, ROS can activate the Nf-kB cascade that plays a central role in the regulation of genes encoding proinflammatory cytokines, adhesion molecules, and inducible nitric oxide synthase enzyme, among others. Our hypothesis is that both regular continuous and high intensity interval aerobic exercise activate the Nrf2 cascade, thereby increasing the host's anti-oxidant defenses, creating an anti-inflammatory environment, while decreasing the activation of the proinflammatory cascade of Nf- kB, both in an experimental model of chronic allergic inflammation and of pulmonary infection by Streptococcus pneumoniae (S. pneumoniae).herefore, our objective is to evaluate the role of aerobic physical exercise in antioxidant defense in experimental models of chronic allergic inflammation and pulmonary infection by S. pneumoniae. For the chronic allergic inflammation project, BALB / C mice sensitized to ovalbumin and submitted to a protocol of continuous aerobic physical exercise will be used. For the S. pneumoniae infection protocol, the animals (BALB / C mice) will first be submitted to the protocol of continuous aerobic physical exercise and then be challenged with this bacterium. The antioxidant anti-inflammatory response will be evaluated through measurements of pulmonary mechanics, bronchoalveolar lavage, immunohistochemistry, immunoassay by ELISA, Western blotting and gene expression. (AU)