Oxidative stress in the pathogenesis of diffuse lung diseases: A review

Abstract

Oxidative stress is an imbalance between oxidants (reactive oxygen and nitrogen species) and antioxidants that may affect lipids, DNA, carbohydrates and proteins. The lung is continuously exposed to endogenous and exogenous oxidants (cigarette smoke, mineral dust, ozone, radiation). Reactive oxygen and nitrogen species are mainly produced by phagocytes as well as by polymorphonuclear, alveolar, bronchial and endothelial cells. A potential role of oxidative stress in the pathogenesis of diffuse lung diseases (particularly idiopathic pulmonary fibrosis) has been demonstrated. Increased oxidant levels and decreased antioxidant defences can contribute to the progression of idiopathic pulmonary fibrosis and other diffuse lung diseases. The growing number of papers on the different aspects of oxidant/antioxidant imbalance in diffuse lung diseases in the last decade reflects increasing interest in this topic and suggests that specific DLDs may be characterized by specific patterns of oxidation and antioxidant responses. The study of oxidative stress can provide insights into etiopathogenesis and favour the discovery of new treatments. In this review of the literature on oxidants and antioxidants in diffuse lung diseases, the focus is on idiopathic pulmonary fibrosis, sarcoidosis, pneumoconiosis and pulmonary fibrosis associated with systemic sclerosis.

Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice

“…An important question is why Elovl6 À / À mice manifest pulmonary fibrosis at baseline and are highly susceptible to BLM compared with WT mice. One possible explanation is that Elovl6 deletion per se causes apoptosis of alveolar epithelial cells and/or induces TGF-b1 production in these cells, given that apoptosis and TGF-b1 production in alveolar epithelial cells largely contributes to the development of fibrosis [4][5][6][7][8][9] . Hence, we compared fluorescent TUNEL staining and caspase 3 activity between WT or Elovl6 À / À lungs before and after BLM instillation.…”

“…Likewise, Kuwano et al 5 demonstrated that caspase inhibitor protected progression of fibrosis in the rodent model. Moreover, alveolar epithelial cells produce transforming growth factor (TGF)-b1, which has a crucial role in lung fibrinogenesis [6][7][8][9] . Furthermore, the role of reactive oxygen species (ROS) and apoptosis in alveolar epithelial cells has been well appreciated as an initiation step of pulmonary fibrosis.…”

Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Curcumin and α-Tocopherol

“…Oxidants include ROS and reactive nitrogen species (RNS) which can be produced by both endogenous sources (inflammatory cells, fibroblast, epithelial cells, endothelial cells, respiratory chain, xanthine and NADPH oxidase) and exogenous sources (cigarette smoke, exogenous toxins, pollution, radiation, carcinogens and drugs) [16]. Under normal physiological conditions, oxidants are scavenged through antioxidant defense mechanism [17].…”

Oxymatrine attenuates bleomycin-induced pulmonary fibrosis in mice via the inhibition of inducible nitric oxide synthase expression and the TGF-β/Smad signaling pathway

“…Oxidative stress plays a key role in the BLM-induced pulmonary inflammation and fibrosis since excess levels of reactive oxygen species (ROS) can non-specifically oxidize cellular macromolecules such as DNAs, lipids, and proteins, leading to oxidative stress-induced tissue injury (34,35). BLM is known to produce ROS during the process of reaction with DNA, thereby causing direct injuries to lung cells and matrix (31).…”