Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in preclinical in vitro and in vivo models and in different clinical trials. This review discusses the role of oxidative stress in the development and progression of IPF and its underlying mechanisms as well as the evidence of oxidative stress in human IPF. Finally, we analyze the mechanism of action, the efficacy and the current status of different drugs developed to inhibit the oxidative stress as anti-fibrotic therapy in IPF.
Highlights
Idiopathic pulmonary fibrosis is the major idiopathic interstitial pneumonia with no cause identified and it is characterized by cellular proliferation, interstitial inflammation, and a chronic and progressive fibrosis
Several studies have suggested that increased oxidative stress may play a central role in the development and progression of Idiopathic pulmonary fibrosis (IPF); cellular participants in lung fibrosis show, in most cases, an imbalance between oxidants and antioxidants
Several reactive oxygen species (ROS) scavengers and modulators of the antioxidant machinery have been tested as potential therapeutics for lung fibrosis in preclinical in vitro and in vivo models and in different clinical trials
Summary
Among all the idiopathic interstitial pneumonias, the most common form is idiopathic pulmonary fibrosis (IPF), whose incidence is estimated to be ranged between 2.8 and 9.3 per 100,000 people per year in North America and Europe (Barratt et al, 2018). Current studies suggest that fibrosis may result from the presence of continuous stimuli (both endogenous and exogenous) or injury followed by an aberrant wound healing process and a dysregulated repair/remodelling of the lung (Kinnula et al, 2005; Kliment and Oury, 2010). Lung fibrosis is associated with accumulation of fibroblasts, myofibroblast activation or differentiation, alveolar reepithelization, extracellular matrix (ECM) dysregulation, oxidative stress, and inflammation (Phan, 2002; Manni and Oury, 2014). Most studies have focused on the fibrotic process and the proliferation of fibroblast and myofibroblast, several studies suggest that increased oxidative stress may play a major role in the development and progression of IPF (Bocchino et al, 2010; Liguori et al, 2018; Cameli et al, 2020). This review addresses the importance of the balance of oxidants/antioxidants in the pathogenesis of pulmonary fibrosis as well as the evidence of oxidative stress in human IPF with emphasis on the pharmacological approach targeting oxidative stress
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