Increased sensitivity to asbestos-induced lung injury in mice lacking extracellular superoxide dismutase

Our plain-English summary of Increased sensitivity to asbestos-induced lung injury in mice lacking extracellular superoxide dismutase, by C.L. Fattman, R.J. Tan, J.M. Tobolewski, et al (Free Radical Biology & Medicine, 2006).

The study

• Authors: C.L. Fattman, R.J. Tan, J.M. Tobolewski, T.D. Oury
• Journal: Free Radical Biology & Medicine
• Published: 2006;40(4):601-7
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestosis is a chronic form of interstitial lung disease characterized by inflammation and fibrosis that results from the inhalation of asbestos fibers. Although the pathogenesis of asbestosis is poorly understood, reactive oxygen species may mediate the progression of this disease. The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) can protect the lung against a variety of insults; however, its role in asbestosis is unknown. To determine if EC-SOD plays a direct role in protecting the lung from asbestos-induced injury, intratracheal injections of crocidolite were given to wild-type and ec-sod-null mice. Bronchoalveolar lavage fluid (BALF) from asbestos-treated ec-sod-null mice at 24 h, 14 days, or 28 days posttreatment showed increased inflammation and total BALF protein content compared to that of wild-type mice. In addition, lungs from ec-sod-null mice showed increased hydroxyproline content compared to those of wild-type mice, indicating a greater fibrotic response. Finally, lungs from ec-sod-null mice showed greater oxidative damage, as assessed by nitrotyrosine content compared to those of their wild-type counterparts. These results indicate that depletion of EC-SOD from the lung increases oxidative stress and injury in response to asbestos.

In plain English

This was an animal experiment in mice. Male C57BL/6 wild-type mice and ec-sod-null mice (lacking extracellular superoxide dismutase, EC-SOD), 8-10 weeks old, were given 0.1 mg of NIEHS crocidolite asbestos (fibers longer than 10 micrometres) by intratracheal instillation, with titanium dioxide or saline as control treatments, and were examined 24 hours, 14 days or 28 days afterwards (3-5 mice per group for lavage analyses). At 28 days after exposure, asbestos-treated wild-type mice had lower lung EC-SOD protein and activity than titanium dioxide controls. Compared with asbestos-treated wild-type mice, asbestos-treated ec-sod-null mice had more total protein in bronchoalveolar lavage fluid at 24 hours and 28 days, more neutrophils at 24 hours and 28 days, more lymphocytes at 28 days, a higher pathology index at 28 days (1.25 plus or minus 0.12 versus 0.79 plus or minus 0.04), higher lung hydroxyproline at 28 days (331.3 plus or minus 14.3 mg versus 274.4 plus or minus 20.5 mg, units as printed, with the error figures given as standard errors), and more nitrotyrosine at 24 hours and 14 days. The authors concluded that loss of EC-SOD exacerbates conditions leading to fibrotic lung disease.

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: Animal experiment comparing wild-type and ec-sod-null (knockout) mice given asbestos
• Who was studied: Male C57BL/6 wild-type mice and ecsod-null mice congenic with C57BL/6, 8-10 weeks old; 3-5 mice per group for lavage, 4-6 per group for other assays; University of Pittsburgh laboratory
• Exposure: Single intratracheal instillation of 0.1 mg NIEHS crocidolite asbestos (fibers longer than 10 micrometres); controls received 0.1 mg titanium dioxide (24 h, 14 days) or 0.9% saline (28 days)
• Main results:
  • At 28 days after exposure, lung homogenates from asbestos-treated wild-type mice had significantly less EC-SOD protein than titanium dioxide controls, and lung EC-SOD activity was also significantly decreased
  • Total bronchoalveolar lavage fluid protein was higher in asbestos-treated ec-sod-null mice than wild-type mice at 24 h (0.546 plus or minus 0.019 wild-type versus 0.851 plus or minus 0.191 knockout) and at 28 days (0.124 plus or minus 0.011 versus 0.209 plus or minus 0.017; p less than 0.05)
  • Asbestos-treated ec-sod-null mice had more lavage neutrophils than wild-type mice at 24 h (0.785 plus or minus 0.87 wild-type versus 1.187 plus or minus 0.124 knockout) and at 28 days (0.396 plus or minus 0.010 versus 0.650 plus or minus 0.084), and more lymphocytes at 28 days (0.0181 plus or minus 0.003 versus 0.0484 plus or minus 0.005), p less than 0.05
  • At 28 days, the pathology index was higher in asbestos-treated ec-sod-null mice (1.25 plus or minus 0.12) than wild-type mice (0.79 plus or minus 0.04), p less than 0.05
  • At 28 days posttreatment, lung hydroxyproline was higher in asbestos-treated ec-sod-null mice (331.3 plus or minus 14.3 mg, unit as printed) than in wild-type mice (274.4 plus or minus 20.5 mg), p less than 0.05
  • Error figures reported in the study are standard errors
  • Lungs of asbestos-treated ec-sod-null mice had higher nitrotyrosine levels than wild-type mice at both 24 h and 14 days (p less than 0.05)
• The authors' conclusion: The authors concluded that loss of EC-SOD worsens conditions leading to fibrotic lung disease and that this supports their hypothesis that EC-SOD protects against the development of asbestosis
• Limitations the authors state:
  • The authors stated the mechanism of the increased nitrotyrosine was not established, and that the increase could instead result from the greater neutrophilia in ec-sod-null mice
  • The authors stated they had not determined whether EC-SOD depletion causes the inflammatory response or results from it

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Superoxide, Interstitial Lung Disease, Inflammation, Fibrosis, Reactive Oxygen Species (ROS), Crocidolite, Bronchoalveolar Lavage (BAL), Oxidative Stress.

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• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)

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