Oxidative Imbalance as a Crucial Factor in Inflammatory Lung Diseases: Could Antioxidant Treatment Constitute a New Therapeutic Strategy?

Tatiana Victoni,Vincent Lagente,Emiliano Barreto,Vinicius F Carvalho,Jayeeta Ghose

doi:10.1155/2021/6646923

Abstract

Inflammatory lung disease results in a high global burden of death and disability. There are no effective treatments for the most severe forms of many inflammatory lung diseases, such as chronic obstructive pulmonary disease, emphysema, corticosteroid-resistant asthma, and coronavirus disease 2019; hence, new treatment options are required. Here, we review the role of oxidative imbalance in the development of difficult-to-treat inflammatory lung diseases. The inflammation-induced overproduction of reactive oxygen species (ROS) means that endogenous antioxidants may not be sufficient to prevent oxidative damage, resulting in an oxidative imbalance in the lung. In turn, intracellular signaling events trigger the production of proinflammatory mediators that perpetuate and aggravate the inflammatory response and may lead to tissue damage. The production of high levels of ROS in inflammatory lung diseases can induce the phosphorylation of mitogen-activated protein kinases, the inactivation of phosphoinositide 3-kinase (PI3K) signaling and histone deacetylase 2, a decrease in glucocorticoid binding to its receptor, and thus resistance to glucocorticoid treatment. Hence, antioxidant treatment might be a therapeutic option for inflammatory lung diseases. Preclinical studies have shown that antioxidants (alone or combined with anti-inflammatory drugs) are effective in the treatment of inflammatory lung diseases, although the clinical evidence of efficacy is weaker. Despite the high level of evidence for the efficacy of antioxidants in the treatment of inflammatory lung diseases, the discovery and clinical investigation of safer, more efficacious compounds are now a priority.

Highlights

Airway inflammation is acknowledged to have a causative role in the pathophysiology of several major lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), allergic rhinitis, cystic fibrosis, cough, emphysema, and lung fibrosis
The chronic inflammation in COPD involves the infiltration of the main types of inflammatory cell into the airway and the lung tissue; the cells can be detected in bronchoalveolar fluid and induced sputum [2]
We previously demonstrated the inability of phagocytes from p47phox-/- knockout mice to produce large quantities of reactive oxygen species (ROS) via the NADPH oxidase (NOX) pathway, which inhibits the development of bleomycin-induced pulmonary fibrosis

Summary

Introduction

Airway inflammation is acknowledged to have a causative role in the pathophysiology of several major lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), allergic rhinitis, cystic fibrosis, cough, emphysema, and lung fibrosis. The chronic inflammation in COPD involves the infiltration of the main types of inflammatory cell (including neutrophils, monocytes/macrophages, and lymphocytes) into the airway and the lung tissue; the cells can be detected in bronchoalveolar fluid and induced sputum [2]. The intactness of basement membrane reflects the dynamic balance between synthesis and degradation of its components—mainly proteases and antiproteases These enzymes are synthesized constitutively by mesenchymal cells (such as fibroblasts, macrophages, endothelial cells, and epithelial cells) and inflammatory cells (such as monocytes/macrophages, neutrophils, and eosinophils) [6]. More recent data in mice favor a role for inflammasome-independent induction of IL-1β in driving smoke-induced inflammation [10] This is in line with a recent study that showed that a monoclonal antibody neutralizing IL-1β was ineffective in the treatment of stable COPD [11]. The objective of the present chapter is to assess the involvement of oxidative imbalance and ROS in the development of respiratory diseases and review new potential treatments or adjunct therapies based on antioxidant compounds

The Role of ROS in the Development of

The Impact of ROS on Glucocorticoid

Could Antioxidant Treatment Be Effective in Lung Diseases?

Concluding Remarks