Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors

Our plain-English summary of Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors, by P.S. Gilmour, D.M. Brown, P.H. Beswick, et al (Environmental Health Perspectives, 1997).

The study

• Authors: P.S. Gilmour, D.M. Brown, P.H. Beswick, W. MacNee, I. Rahman, K. Donaldson
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1313-7
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We studied asbestos, vitreous fiber (MMVF10), and refractory ceramic fiber (RCF1) from the Thermal Insulation Manufacturers' Association fiber repository regarding the following: free radical damage to plasmid DNA, iron release, ability to deplete glutathione (GSH), and activate redox-sensitive transcription factors in macrophages. Asbestos had much more free radical activity than any of the man-made vitreous fibers. More Fe3+ was released than Fe2+ and more of both was released at pH 4.5 than at pH 7.2. Release of iron from the different fibers was generally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stress, as revealed by depletion of intracellular GSH. Amosite asbestos upregulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the only fiber to enhance activation of the transcription factor nuclear factor kappa B (NF kappa B). The use of cysteine methyl ester and buthionine sulfoximine to modulate GSH suggested that GSH homeostasis was important in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of transcription factor activation and therefore gene expression in alveolar macrophages. Although this was not related to iron release or ability to deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.

In plain English

This was a laboratory study. The authors compared long-fiber amosite asbestos with a man-made vitreous fiber (MMVF10) and a refractory ceramic fiber (RCF1), used at equal fiber numbers. They tested free radical damage to DNA in a test-tube assay and measured iron release. They also exposed alveolar macrophages (lung immune cells) taken from Wistar rats to the fibers. Amosite depleted 85% of the intact (supercoiled) DNA, compared with 10% in untreated controls. RCF1 and MMVF10 caused significantly less damage. RCF1 released significantly more iron than amosite, and the authors saw no apparent link between iron release and free radical activity. All three fibers lowered the cells' glutathione, an antioxidant. Amosite increased nuclear translocation (movement into the cell nucleus) of the transcription factor AP-1 by 37.4% over untreated controls, against 11.9% for MMVF10 and 9.1% for RCF1. In ordinary cells, only amosite activated the transcription factor NF-kappa B, though RCF1 also did after glutathione was first depleted. The authors concluded that asbestos had more hydroxyl radical activity than the two man-made fibers and that iron did not appear to determine this.

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: laboratory (in vitro) experiment: a cell-free plasmid DNA assay, iron release measurements, and cultured rat alveolar macrophages
• Who was studied: alveolar macrophages obtained by lung lavage from adult Wistar rats (in-house-bred), plus plasmid DNA in a cell-free assay; no human subjects
• Exposure: long-fiber amosite asbestos, man-made vitreous fiber MMVF10 and refractory ceramic fiber RCF1 (the man-made fibers came from the TIMA fiber repository), used at equal fiber numbers: 9.3 x 10^5 fibers per DNA assay, 8.24 x 10^7 per ml for iron detection, and 8.24 x 10^6 per ml for glutathione and gel mobility shift assays
• Main results:
  • Amosite asbestos caused 85% depletion of supercoiled DNA, compared with 10% for untreated controls (p less than 0.001); this was partly attributable to hydroxyl radicals and fiber-associated iron
  • RCF1 and MMVF10 were significantly less able than amosite to produce free radicals in the DNA assay (p less than 0.001)
  • All fibers released more Fe3+ than Fe2+, and released more iron at pH 4.6 than at pH 7.2
  • Iron release did not appear to correlate with free radical activity; RCF1 released significantly more of both forms of iron than long-fiber amosite
  • All three fibers significantly lowered glutathione inside the rat macrophages (p less than 0.01), with MMVF10 causing the greatest depletion
  • Compared with untreated control cells, nuclear translocation of AP-1 rose 11.9% with MMVF10, 9.1% with RCF1 and 37.4% with long-fiber amosite
  • In ordinary fiber treatment, only long-fiber amosite activated NF-kappa B; MMVF10 and RCF1 had no effect
  • When the cells' glutathione was first lowered with BSO, NF-kappa B activation by amosite increased, and RCF1 produced activation almost double that of the BSO-alone control; when glutathione was raised with CME, NF-kappa B activation by amosite was almost eliminated
• The authors' conclusion: The authors concluded that the hydroxyl radical activity of asbestos exceeded that of MMVF10 and RCF1, and that iron did not appear to determine this free radical potential or the fibers' relative pathogenicity. They said the greater free radical activity of amosite was mirrored in transcription factor activation, but that the exact role of glutathione remained to be worked out.
• Limitations the authors state:
  • The single 4-hour time point may not have captured the most important change in glutathione
  • The mechanism of the activation cascade and how different fiber properties produce different cell responses require further study

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress, Vitreous, Thermal System Insulation (TSI), Glutathione (GSH), Macrophage, Amosite, Nuclear Factor kappa B (NF-κB), Alveolar Macrophage.

Related studies

• Free radical activity of synthetic vitreous fibers: iron chelation inhibits hydroxyl radical generation by refractory ceramic fiber — D.M. Brown, C. Fisher, et al. (1998)
• Enhancement of the macrophage oxidative burst by immunoglobulin coating of respirable fibers: fiber-specific differences between asbestos and man-made fibers — I.M. Hill, P.H. Beswick, et al. (1996)
• The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy — S. Toyokuni (2016)
• Free radical activity associated with the surface of particles: a unifying factor in determining biological activity? — K. Donaldson, P.H. Beswick, et al. (1996)
• Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress — W.A. Swain, K.J. O'Byrne, et al. (2004)
• Detection of surface free radical activity of respirable industrial fibres using supercoiled phi X174 RF1 plasmid DNA — P.S. Gilmour, P.H. Beswick, et al. (1995)

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