Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases

Our plain-English summary of Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases, by A. Shukla, M. Gulumian, T.K. Hei, et al (Free Radical Biology & Medicine, 2003).

The study

• Authors: A. Shukla, M. Gulumian, T.K. Hei, D. Kamp, Q. Rahman, B.T. Mossman
• Journal: Free Radical Biology & Medicine
• Published: 2003;34(9):1117-29
• Type of article: Review
• Cited by: 207 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos.

In plain English

This article was a review, part of a journal series on oxidants in lung injury and disease. It gathered earlier laboratory research, mostly in cell cultures and animals, on how asbestos fibers produce reactive oxygen and nitrogen species (oxidants) and how these may contribute to asbestosis, lung cancer and mesothelioma. It described the six recognized asbestos types. It reviewed evidence that the form of iron in fibers such as crocidolite and amosite governs oxidant production, with ferrous iron on the fiber surface most active. It also summarized studies linking oxidants to DNA damage, mutations, cell death, inflammation and cell signaling. The review presented laboratory data in human-hamster hybrid (AL) cells. Crocidolite caused release of hydrogen peroxide, and the enzyme catalase reduced this release 7- to 8-fold. Both crocidolite and hydrogen peroxide produced dose-dependent mutations. At the doses tested, titanium dioxide was neither toxic nor mutagenic to these cells (data not shown). The authors concluded that there is strong evidence that oxidants contribute to asbestos-induced lung injury, and that reducing oxidant stress may lessen asbestos's harmful effects. They noted that the disease mechanisms are still not fully understood.

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: Narrative review of laboratory (cell culture and animal) research on oxidants and asbestos, published as part of a serial review; it also includes cell-culture data shown in Fig. 1
• Who was studied: Published studies in animal models and cell cultures, including rodent lungs and lung epithelial, mesothelial and macrophage cells; the presented experiment used human-hamster hybrid (AL) cells
• Exposure: Asbestos fibers: chrysotile, amosite, crocidolite, tremolite, anthophyllite and actinolite, with particular attention to iron-containing types (crocidolite, amosite)
• Main results:
  • From the studies reviewed, the authors summarized that the ionic state of iron in asbestos determines its ability to generate oxidants, and that ferrous iron on the fiber surface is most active
  • In a reviewed study, the ability of fibers to generate hydroxyl radical was ranked in the order crocidolite, amosite, tremolite, anthophyllite, chrysotile. The comparison symbols between the fiber names are lost in the text.
  • In crocidolite-exposed AL cells, adding catalase reduced hydrogen peroxide release 7- to 8-fold. Heat-inactivated catalase had no effect.
  • In AL cells, crocidolite fibers and hydrogen peroxide each caused a dose-dependent increase in CD59 mutants. The data were pooled from three independent experiments.
  • The negative control, titanium dioxide, was neither cytotoxic nor mutagenic to AL cells at the doses tested (up to 12 per square centimetre of dish; the unit symbol is lost in the text) under similar conditions. The authors did not show these data.
  • In a reviewed inhalation study, animals exposed to crocidolite that received polyethylene glycol-conjugated catalase showed significantly less lung injury, inflammation and pulmonary fibrosis. The article describes the animals first as rats and then as mice.
  • Reviewed studies found strong staining for nitrotyrosine, a marker of peroxynitrite formation, in the lungs of rats exposed to chrysotile and crocidolite
  • Reviewed studies found that iron chelators and free radical scavengers reduced asbestos-induced death of alveolar epithelial cells and mesothelial cells
• The authors' conclusion: The authors concluded that there is strong evidence that oxidants contribute to asbestos-induced lung injury, and that strategies to reduce oxidant stress in lung cells may lessen the harmful effects of asbestos. They also proposed that the balance between oxidative stress and antioxidant defense presumably determines whether lung or pleural disease occurs.
• Limitations the authors state:
  • The authors stated that how asbestos-related diseases develop is still poorly understood
  • The authors stated that the nature of the radical-generating surface sites on asbestos fibers is not yet clear
  • The authors stated that the mechanisms by which iron-derived oxidants trigger cell death are not fully established
  • The authors noted that protective approaches shown in rodents leave open how to curb ongoing oxidant production in heavily exposed people, and that retinoid trials have been controversial

Topics

Medical terms in this study, explained in our Lexicon: Bronchogenic Carcinoma, Mesothelioma, Apoptosis, Inflammation.

Related studies

• N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers — F. Afaq, P. Abidi, et al. (2000)
• Inflammation and cancer — M. Murata (2018)
• Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells — S.J. Kim, P. Cheresh, et al. (2014)
• Oxidants and signaling by mitogen-activated protein kinases in lung epithelium — B.T. Mossman, K.M. Lounsbury, et al. (2006)
• Increased mineral dust-induced production of reactive oxygen species by blood monocytes from patients with malignant diseases — P.W. Nyberg, S.A. Nordman, et al. (1994)
• Role of oxidants in interstitial lung diseases: pneumoconioses, constrictive bronchiolitis, and chronic tropical pulmonary eosinophilia — W.N. Rom (2011)

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