Oxidative Stress in Pulmonary Fibrosis

Abstract

Idiopathic ulmonary fibrosis (histopathology of usual interstitial pneumonia) is a progressive lung disease of unknown etiology. No treatment has been shown to improve the prognosis of the patients with this disease. Recent evidence, including the observations that the patients with idiopathic pulmonary fibrosis have higher levels of oxidant stress than control patients, and a recent multicenter European study examining the effect of the antioxidant N-acetylcysteine on the progression of idiopathic pulmonary fibrosis suggest that the cellular redox state may play a significant role in the progression of this disease. These complex mechanisms include activation of growth factors as well as regulation of matrix metalloproteinases and protease inhibitors. Potential future approaches for the therapy of interstitial pulmonary fibrosis may involve synthetic agents able to modulate cellular redox state. Investigation into therapeutic approaches to inhibit oxidant-mediated reactions in the initiation and progression of pulmonary fibrosis may provide hope for the future treatment of this disease.Keywords: antioxidant; idiopathic pulmonary fibrosis; oxidant; radical Idiopathic pulmonary fibrosis (IPF) is a prototype of idiopathic interstitial pneumonias, a chronic disease of the lung parenchyma that leads to diffuse scarring and end-stage tissue fibrosis (1). Typical features in this disease include dyspnea, diffuse interstitial infiltrates, progressive lung fibrosis, and poor prognosis. The pathologic changes in IPF include patchy fibrotic lesions that vary both in age and activity, and only weak inflammation. The focal zones of fibroblast proliferation are called "fibroblastic foci" and appear to occur at sites of recent alveolar injury (1, 2). The biochemical mechanisms in the pathogenesis of IPF are still poorly understood and medical therapies have thus far offered little if any benefit against the progression of this disease (1,3,4).As the name implies, there is no known etiologic stimulus that initiates this disease. Current evidence suggests that both endogenous and exogenous stimuli may injure the alveolar epithelium. This is followed by an abnormal repair process in individuals unable to effectively heal the damage. The majority of the original articles and reviews on IPF have focused on the (Received in original form January 5, 2005; accepted in final form May 3, 2005) This and the original studies of V.L.K.

Oxidative Stress Alters Syndecan-1 Distribution in Lungs with Pulmonary Fibrosis

“…2). Oxidative stress contributes to mouse models of fibrosis, IPF, and other pulmonary diseases (5,(47)(48)(49). We have demonstrated that EC-SOD inhibits syndecan-1 shedding and reduces BALF neutrophil influx in vivo (Fig.…”

“…IPF patients have a mean survival of 3-5 years (1,2) and no effective therapies (3,4), other than orthotopic lung transplantation, have proven to improve survival. The pathogenesis of IPF is poorly understood; however, inflammation and oxidant/antioxidant imbalances in the lung are thought to play important roles (5)(6)(7). A better understanding of the molecular mechanisms involved in oxidative injury and fibrosis could lead to the development of novel therapeutic targets.…”

Extracellular Superoxide Dismutase Inhibits Inflammation by Preventing Oxidative Fragmentation of Hyaluronan

“…An important factor in determining the surface and biological reactivity of asbestos fibers is their ability to participate in redox reactions that generate free radicals. Free radicals generated from asbestos fibers and/or damage by fibers are linked to cell signaling, inflammation, and a plethora of other responses associated with the pathogenesis of asbestos-associated diseases (10,(12)(13)(14)(15)(16)(17). The oxidative stress-related nature of asbestos-associated lung injury makes it a good model to study the possible relationship between free radical-induced hyaluronan degradation and the possible protective effects of antioxidants in vivo.…”

The Ethical Kampo Formulation Sho-Seiryu-To (TJ-19) Prevents Bleomycin-Induced Pulmonary Fibrosis in Rats

“…12) Reactive oxygen species (ROS) play a crucial role in the development of pulmonary fibrosis induced by BLM. 5) In this study, we observed an increase in MDA content in the lung after BLM injection; however, this increase was attenuated by TJ-19 administration. This result suggests that the preventive effects of TJ-19 on BLM-induced pulmonary fibrosis, at least in part, can be ascribed to antioxidative potential.…”