Extracellular superoxide dismutase in pulmonary fibrosis

Our plain-English summary of Extracellular superoxide dismutase in pulmonary fibrosis, by F. Gao, V.L. Kinnula, M. Myllärniemi, et al (Antioxidants & Redox Signaling, 2008).

The study

• Authors: F. Gao, V.L. Kinnula, M. Myllärniemi, T.D. Oury
• Journal: Antioxidants & Redox Signaling
• Published: 2008;10(2):343-54
• Type of article: Review
• Cited by: 97 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Disruption of the oxidant/antioxidant balance in the lung is thought to be a key step in the development of many airway pathologies. Hence, antioxidant enzymes play key roles in controlling or preventing pulmonary diseases related to oxidative stress. The superoxide dismutases (SOD) are a family of enzymes that play a pivotal role protecting tissues from damage by oxidant stress by scavenging superoxide anion, which prevents the formation of other more potent oxidants such as peroxynitrite and hydroxyl radical. Extracellular SOD (EC-SOD) is found predominantly in the extracellular matrix of tissues and is ideally situated to prevent cell and tissue damage initiated by extracellularly produced ROS. EC-SOD has been shown to be protective in several models of interstitial lung disease, including pulmonary fibrosis. In addition, alterations in EC-SOD expression are also present in human idiopathic pulmonary fibrosis (IPF). This review discusses EC-SOD regulation in response to pulmonary fibrosis in animals and humans and reviews possible mechanisms by which EC-SOD may protect against fibrosis.

In plain English

This article is a review, not a new study. The authors reviewed published research on extracellular superoxide dismutase (EC-SOD), an antioxidant enzyme found mainly in the tissue framework of the lung. They covered animal models of pulmonary fibrosis and human idiopathic pulmonary fibrosis (IPF). In the asbestos section, they described rodent studies in which crocidolite asbestos was instilled into the windpipe. Studies they cited reported that mice lacking EC-SOD showed more lung damage, inflammation and fibrosis than normal (wild-type) mice after asbestos exposure, and that asbestos injury led to a rapid loss of EC-SOD from lung tissue. Similar findings were cited for bleomycin, a drug used to cause lung fibrosis in mice. In human IPF lungs, cited work found EC-SOD low or absent in fibrotic areas. The authors concluded that low EC-SOD in IPF lungs may contribute to antioxidant imbalances that result in further progression of the disease. They noted that animal models show more inflammation than human IPF and are often reversible. They also noted that a study of an EC-SOD gene variant in IPF patients did not have enough statistical power to rule out a role for that variant in lung fibrosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review article (Forum Review) of published experimental and human studies
• Who was studied: No study population of its own. The review covered published studies in experimental animal models of pulmonary fibrosis (mainly mice and rats) and studies of human IPF lungs.
• Exposure: Oxidative stress in lung fibrosis models: hyperoxia, bleomycin, radiation and asbestos. The asbestos models discussed used crocidolite asbestos instilled into the trachea of rodents. Chrysotile is described only as background.
• Main results:
  • Cited studies (not new data) reported that mice lacking EC-SOD had more lung damage, inflammation and fibrosis than wild-type mice after asbestos-induced lung injury.
  • Cited work reported that asbestos injury in mice led to a rapid loss of EC-SOD from the lung interstitium.
  • Cited studies reported more bleomycin-induced lung damage in mice lacking EC-SOD.
  • In human UIP/IPF lungs, cited work found EC-SOD expression low or absent in fibrotic areas and fibroblastic foci.
• The authors' conclusion: The authors concluded that the low level of interstitial EC-SOD in IPF lungs may contribute to antioxidant imbalances that result in further progression of the disease.
• Limitations the authors state:
  • The authors noted that experimental fibrosis models show more inflammation than human IPF and are frequently reversible.
  • The authors noted that a cited study of an EC-SOD gene polymorphism in UIP/IPF patients and controls was not powered to exclude a role for the polymorphism in lung fibrosis, and that larger patient series are needed.

Topics

Medical terms in this study, explained in our Lexicon: Superoxide, Pulmonary Fibrosis, Oxidative Stress, Peroxynitrite, Hydroxyl Radical, Interstitial Lung Disease, Idiopathic, Fibrosis.

Related studies

• Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan — F. Gao, J.R. Koenitzer, et al. (2008)
• Inflammatory cells as a source of airspace extracellular superoxide dismutase after pulmonary injury — R.J. Tan, J.S. Lee, et al. (2006)
• Leukocyte-derived extracellular superoxide dismutase does not contribute to airspace EC-SOD after interstitial pulmonary injury — M.L. Manni, M.W. Epperly, et al. (2012)
• Extracellular superoxide dismutase protects against matrix degradation of heparan sulfate in the lung — C.R. Kliment, J.M. Tobolewski, et al. (2008)
• Mitochondrial Cu,Zn-superoxide dismutase mediates pulmonary fibrosis by augmenting H2O2 generation — C. He, S. Murthy, et al. (2011)
• Manganese and extracellular superoxide dismutase polymorphisms and risk for asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2009)

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