Is the leukotrienes via contributes to the anti-inflammatory effects of aerobic exercise in asthma?

• Grant number: 12/21519-1
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2013
• Effective date (End): January 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rodolfo de Paula Vieira
• Grantee: Ricardo Wesley Alberca Custódio
• Host Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil
• Associated scholarship(s): 14/09292-7 - Application of in vivo imaging, a central technique for pre-clinical studies, in a model of pulmonary fibrosis, BE.EP.MS

Abstract

In the last years a growing number of studies have demonstrated that aerobic physical training (APT), when performed in a proper intensity, duration and frequency, results in several benefits to asthmatic patients, including improvement in health releated quality of life, decrease of anxiety and depression, improvement of minute ventilation, decrease in the number of crisis, decrease in the levels of exhaled nitric oxide, beyond to decrease the needing of corticosteroids. Recently, was demonstrated for the first time that APT results in a direct anti-inflammatory effects on the airways of asthmatic patients, since that APT reduced the number of eosinophils in induced sputum of these patients. However, several questions and hypothesis were raised up concerning the possible mechanisms involved in this anti-inflammatory effect of APT in asthma. In this way, a growing number of studies using experimental models of asthma have been published, which are demonstrating possible mechanisms involved in the effects of APT in asthma. However, until this moment no study has evaluated the effects of APT on leukotrienes pathway in asthma. Therefore, the present study aims to evaluate if the anti-inflammatory effects of APT in asthma is mediated, at least partially, by the inhibition of leukotrienes or even by the inhibition of leukotrienes receptors. Then, 60 BALB/c male mice will be distributed in 4 experimental groups (Control, n = 20), (Exercise, n = 20), (Asthma, n = 20) and (Asthma + Exercise, n = 20). The experimental model of "asthma" (chronic allergic airway inflammation) will be induced through intra-peritoneal injection of ovalbumin on days 0 and 14, followed by inhalation of ovalbumin solution (1%) for 30 minutes, 3x/week, beginning on day 21 until day 53. Aiming to evaluate the therapeutic effects of APT on airway inflammation and leukotriene pathway, APT of low intensity will be performed 5x/week, 60 minutes/session, beginning on day 27 of experimental protocol until day 53, when the airway inflammation is already established. Twenty-four hours after the last inhalation and APT, the animals will be anesthetized, traqueotomized, canulated and the bronchoalveolar lavage will be collected and analyzed the total and differential cell number. Lung histology will be performed aiming to quantify the number of lymphocytes and eosinophils in the airways.The evaluation of the expression of the proteins involved in the leukotrienes pathway through the western blotting technique in the homogenate of lung tissue will be performed. The proteins are: 5-lipoxygenase (5-LO) e LTC(4) synthase, receptor BLT1, receptor BLT2, receptor cysLT1 e receptor cysLT2. Beyond that, the levels of LTB4 e LTcys in the bronchoalveolar lavage and in lung tissue by using ELISA technique. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALBERCA-CUSTODIO, RICARDO WESLEY; GREIFFO, FLAVIA REGINA; MACKENZIE, BREANNE; OLIVEIRA-JUNIOR, MANOEL CARNEIRO; ANDRADE-SOUSA, ADILSON SANTOS; GRAUDENZ, GUSTAVO SILVEIRA; GOMES SANTOS, ANGELA BATISTA; DAMACENO-RODRIGUES, NILSA REGINA; CASTRO-FARIA-NETO, HUGO CAIRE; ARANTES-COSTA, FERNANDA MAGALHAES; et al. Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway. FRONTIERS IN IMMUNOLOGY, v. 7, JUN 14 2016. (12/15165-2, 14/23196-0, 13/23763-0, 12/23305-9, 14/14604-8, 12/21519-1, 14/09292-7)

ALMEIDA-OLIVEIRA, A. R.; AQUINO, JR., J. C. J.; ABBASI, A.; SANTOS-DIAS, A.; OLIVEIRA, JR., M. C.; ALBERCA-CUSTODIO, R. W.; RIGONATO-OLIVEIRA, N. C.; SALLEY-DIAS, L. P.; DAMACENO-RODRIGUES, N. R.; CALDINI, E. G.; et al. Effects of Aerobic Exercise on Molecular Aspects of Asthma: Involvement of SOCS-JAK-STAT. EXERCISE IMMUNOLOGY REVIEW, v. 25, p. 98-110, 2019. (12/16498-5, 12/15165-2, 14/12755-9, 14/07500-1, 12/21519-1)

OLIVEIRA, JR., MANOEL CARNEIRO; GREIFFO, FLAVIA REGINA; RIGONATO-OLIVEIRA, NICOLE CRISTINE; ALBERCA CUSTODIO, RICARDO WESLEY; SILVA, VANESSA ROZA; DAMACENO-RODRIGUES, NILSA REGINA; ALMEIDA, FRANCINE MARIA; ALBERTINI, REGIANE; LOPES-MARTINS, RODRIGO ALVARO B.; FRANCO DE OLIVEIRA, LUIS VICENTE; et al. Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 134, p. 57-63, MAY 5 2014. (12/21519-1, 12/15165-2, 12/23305-9)