The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages

Our plain-English summary of The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages, by E. Aldieri, I. Fenoglio, F. Cesano, et al (Journal of Toxicology and Environmental Health. Part a, 2013).

The study

• Authors: E. Aldieri, I. Fenoglio, F. Cesano, E. Gazzano, G. Gulino, D. Scarano, A. Attanasio, G. Mazzucco, D. Ghigo, B. Fubini
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2013;76(18):1056-71
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Lung toxicity mediated by multiwalled carbon nanotubes (MWCNT) has been widely demonstrated and recently associated with induction of carcinogenic asbestos-like effects, but the chemical features that drive this toxic effect have still not been well elucidated. The presence of metals as trace contaminants during MWCNT preparation, in particular iron (Fe) impurities, plays an important role in determining a different cellular response to MWCNT. Our goal was to clarify the mechanisms underlying MWCNT-induced toxicity with correlation to the presence of Fe impurities by exposing murine alveolar macrophages to two different MWCNT samples, which differed only in the presence or absence of Fe. Data showed that only Fe-rich MWCNT were significantly cytotoxic and genotoxic and induced a potent cellular oxidative stress, while Fe-free MWCNT did not exert any of these adverse effects. These results confirm that Fe content represents an important key constituent in promoting MWCNT-induced toxicity, and this needs to be taken into consideration when planning new, safer preparation routes.

In plain English

This was a laboratory experiment in cultured mouse alveolar macrophages (MH-S cells). The authors prepared two multiwalled carbon nanotube (MWCNT) samples from the same commercial material, one still containing iron from the catalyst and one from which iron had been removed by mild hydrochloric acid treatment; the article reports the pristine material contained 0.5% Fe and 0.03% Al, and that iron was almost completely removed by the treatment without altering nanotube structure or defect level. Cells were exposed for 24 h to 25-100 micrograms per square centimetre of either sample, with UICC crocidolite asbestos fibres (25 micrograms per square centimetre) as a positive control. Only the iron-rich MWCNT caused a concentration-dependent increase in LDH release, increased TBARS, decreased intracellular glutathione, raised HO-1 expression and DNA damage in the comet assay (tail length 93.0 plus or minus 3.4 micrometres versus 19.7 plus or minus 1.2 for iron-free and 12.3 plus or minus 0.8 for control). Uptake of both samples was similar. The authors concluded iron plays an important role in MWCNT toxicity.

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: in vitro experimental study in a murine alveolar macrophage cell line, with physicochemical characterization of the nanotubes and cell-free ESR tests
• Who was studied: Murine alveolar macrophages (MH-S cell line) grown in culture; no humans or animals were exposed in vivo
• Exposure: Iron-rich and iron-free short multiwalled carbon nanotubes, 25-100 micrograms per square centimetre for 24 h; UICC crocidolite asbestos fibres at 25 micrograms per square centimetre as positive control
• Main results:
  • The pristine (iron-rich) nanotubes contained 0.5% Fe and 0.03% Al from the catalyst; the acid treatment removed almost all the iron
  • Iron-rich MWCNT increased LDH leakage from MH-S cells with increasing dose; the authors report this effect was hardly detectable with equal amounts of iron-free MWCNT
  • Lipid peroxidation (TBARS) rose only with iron-rich MWCNT, not with iron-free MWCNT
  • Intracellular glutathione fell only in cells given iron-rich MWCNT
  • HO-1 protein expression increased with iron-rich MWCNT, as with crocidolite
  • In the comet assay all three DNA-damage indices were higher with iron-rich MWCNT and crocidolite than in controls or with iron-free MWCNT
  • Comet assay values for iron-rich MWCNT: tail length 93.0 ± 3.4 micrometres, tail DNA 17.9 ± 2.0%, tail moment 3.5 ± 0.5 (control 12.3 ± 0.8, 1.7 ± 0.2, 0.34 ± 0.1; iron-free MWCNT 19.7 ± 1.2, 1.6 ± 0.1, 0.54 ± 0.1; crocidolite 129.1 ± 4.5, 20.0 ± 3.5, 5.1 ± 0.3)
  • In the cell-free ESR tests neither sample itself generated radicals, and both removed hydroxyl radicals generated by photolysis of hydrogen peroxide
  • Both nanotube samples, and crocidolite, were taken up by the macrophages to a similar extent, mainly as cytoplasmic agglomerates
• The authors' conclusion: The authors concluded that iron content is a key constituent driving MWCNT-induced cytotoxicity, oxidative stress and DNA damage, and that removing iron impurities during preparation should be considered
• Limitations the authors state:
  • The authors noted that the concentrations tested were relatively higher than those used in animal models, high doses of iron-free MWCNT being used deliberately to rule out their in vitro toxicity

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Carcinogenic, Oxidative Stress.

Related studies

• Iron inhibits the nitric oxide synthesis elicited by asbestos in murine macrophages — E. Aldieri, D. Ghigo, et al. (2001)
• Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages — P.P. Simeonova, M.I. Luster (1995)
• Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure — L. Ju, W. Wu, et al. (2017)
• Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in human mesothelial cells investigated by Synchrotron XRF microscopy — F. Cammisuli, S. Giordani, et al. (2018)
• A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro — T. Thurnherr, C. Brandenberger, et al. (2011)
• Iron-loaded synthetic chrysotile: a new model solid for studying the role of iron in asbestos toxicity — E. Gazzano, F. Turci, et al. (2007)

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