Role of lung oxidative stress as therapeutical target of probiotics Lactobacillus rhamnosus and Bifidobavterium breve in an experimental model of chronic obstructive pulmonary disease.

• Grant number: 19/03402-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2019
• End date: May 31, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Flávio Aimbire Soares de Carvalho
• Grantee: Flávio Aimbire Soares de Carvalho
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• City of the host institution: São José dos Campos
• Associated researchers: Alexandre de Castro Keller

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a syndrome characterized by destruction of the lung parenchyma, reduced ventilation and pulmonary perfusion, and impaired gas exchange capacity. Patients are diagnosed as having chronic bronchitis or pulmonary emphysema. An aggravating factor in COPD is that, although drug therapy is the first treatment option, especially with corticosteroids and bronchodilators, these drugs have little effect on emphysematous patients and are not capable of effectively attenuating the symptoms of the disease. In addition, conventional pharmacological treatment has serious side effects. For this reason, COPD has a high rate of morbidity and mortality, and is one of the main causes of hospitalization and of drug costs in the public health system. The inflammatory response in emphysematous patients is due to chronic exposure to noxious particles or gases, and in this sense smoking is one of the main causes of COPD. The exacerbated airway inflammatory response in COPD is characterized by the presence of inflammatory cells and the secretion of pro-inflammatory mediators in the lung microenvironment. It is now recognized that the progression of alveolar destruction in COPD, even if the emphysema type person ceases smoking, is directly related to the increased metabolism of oxidative stress in bronchial and inflammatory epithelial cells, such as neutrophils and alveolar macrophages. These cells, when activated by cigarette smoke, secrete cytokines, chemokines, proteases, and free radicals. This results in hypersecretion of mucus, loss of pulmonary elasticity, and alveolar depletion due to changes in the balance between the activity of pro- and antioxidant enzymes in the lung. Under these conditions, a growing number of studies have shown that dietary probiotic supplementation may have a beneficial potential to reduce inflammation of chronic lung diseases without presenting side effects. Considering that the imbalance between pro-and antioxidant responses in the exacerbation of oxidative stress metabolism is fundamental for the progression and maintenance of COPD, there is interest understanding whether probiotics are capable of acting as antioxidants in this disease. In this sense, the present project aims to investigate the effect of probiotics Lactobacillus rhamnosus and Bifidobacterium breve on the cellular and molecular mechanisms involved in pulmonary oxidative stress in an experimental model of COPD. (AU)