Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung

Our plain-English summary of Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung, by D. Crouzier, S. Follot, E. Gentilhomme, et al (Toxicology, 2010).

The study

• Authors: D. Crouzier, S. Follot, E. Gentilhomme, E. Flahaut, R. Arnaud, V. Dabouis, C. Castellarin, J.C. Debouzy
• Journal: Toxicology
• Published: 2010;272(1-3):39-45
• Cited by: 60 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

With the rapid spread of carbon nanotubes (CNTs) applications, the respiratory toxicity of these compounds has attracted the attention of many scientists. Several studies have reported that after lung administration, CNTs could induce granuloma, fibrosis, or inflammation. By comparison with the mechanisms involved with other toxic particles such as asbestos, this effect could be attributed to an increase of oxidative stress. The aim of the present work was to test this hypothesis in vivo. Mice were intranasally instilled with 1.5mg/kg of double walled carbon nanotubes (DWCNTs). Six, 24, or 48h after administration, inflammation and localisation of DWCNTs in lungs were microscopically observed. Local oxidative perturbations were investigated using ESR spin trapping experiments, and systemic inflammation was assessed by measuring the plasma concentration of cytokines TNF-alpha, IL-1alpha, IL-1beta, IL-6, IGF-1, Leptin, G-CSF, and VEGF. Examination of lungs and the elevation of proinflammatory cytokines in the plasma (Leptin and IL-6 at 6h) confirmed the induction of an inflammatory reaction. This inflammatory reaction was accompanied by a decrease in the local oxidative stress. This effect could be attributed to the scavenger capability of pure CNTs.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

In plain English

This mouse experiment studied double-walled carbon nanotubes (DWCNTs), not asbestos, which the article mentions only as a comparison. Male Swiss mice had 1.5 mg/kg of nanotubes placed in the nose and were examined 6, 24 or 48 hours later. They were compared with saline-treated controls and with mice given bleomycin as a positive control. Under the microscope, treated lungs showed nanotube clusters and thickened alveolar walls. They also showed more macrophages than controls, though never at an extensive level. Blood leptin was significantly higher than in controls at every time point, and IL-6 was significantly higher at 48 hours. The other cytokines measured did not differ. Free-radical (reactive oxygen species) signals in the lung were lower than in controls. The drop was 19% at 6 hours, which was not statistically significant, then 54% at 24 hours, which was significant, and 55% at 48 hours. In test-tube experiments, the nanotubes produced no detectable radicals and almost completely suppressed radicals made by a chemical reaction. The authors concluded that purified DWCNTs induce lung inflammation but that their ability to trap radicals limits the resulting oxidative stress.

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 (mice), with an added in vitro (test-tube) free-radical experiment
• Who was studied: 40 male Swiss mice, weighing 30 to 35 g, from Charles River, France. Groups were: saline controls, DWCNT-treated mice examined at 6, 24 or 48 hours, and a bleomycin positive-control group examined at 6 hours.
• Exposure: Double-walled carbon nanotubes, given by intranasal instillation at 1.5 mg/kg in saline. The sample was about 80% DWCNTs and 20% single-walled nanotubes, with a few triple-walled nanotubes. No asbestos was tested.
• Main results:
  • Lung free-radical (ROS) signal in DWCNT-treated mice at 6 hours: 19% lower than controls, not statistically significant.
  • Lung ROS signal in DWCNT-treated mice at 24 hours: 54% lower than controls (p less than 0.01). At 48 hours it was 55% lower than controls.
  • Blood leptin was significantly higher in DWCNT-treated mice at all times: control 3954 plus or minus 332 pg/ml; 6 h 5755 plus or minus 385 pg/ml; 24 h 5116 plus or minus 323 pg/ml; 48 h 6381 plus or minus 856 pg/ml.
  • Among the other cytokines, only IL-6 differed: it was significantly higher at 48 hours (517 plus or minus 36 pg/ml for controls vs 709 plus or minus 56 pg/ml for the 48 h group).
  • Treated lungs showed thickened alveolar walls compared with control lungs. This was focal at 6 hours and seen in most of the tissue at 24 and 48 hours.
  • Macrophages were seen more often in DWCNT-treated lungs than in control lungs, but never at an extensive level.
  • In vitro, the nanotubes produced no detectable radicals with hydrogen peroxide, and they almost completely suppressed the radical signal from a Fenton reaction.
• The authors' conclusion: The authors concluded that purified DWCNTs induce an inflammatory reaction in the lungs, but that the nanotubes' ability to scavenge reactive oxygen species limits the resulting oxidative stress.
• Limitations the authors state:
  • Changes in plasma cytokines were limited because cytokines produced in the lung were diluted by the whole blood volume.
  • Without a dispersing agent (BSA), the nanotube structures given to the mice could be bigger than with other methods.
  • Only purified nanotubes were tested; the in vivo effects of unpurified nanotubes still need investigation.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Reactive Oxygen Species (ROS), Granuloma, Fibrosis, Oxidative Stress, Cytokine.

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