The role of free radicals in asbestos-induced diseases

Our plain-English summary of The role of free radicals in asbestos-induced diseases, by D.W. Kamp, P. Graceffa, W.A. Pryor, et al (Free Radical Biology & Medicine, 1992).

The study

• Authors: D.W. Kamp, P. Graceffa, W.A. Pryor, S.A. Weitzman
• Journal: Free Radical Biology & Medicine
• Published: 1992;12(4):293-315
• Type of article: Review
• Cited by: 340 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos exposure causes pulmonary fibrosis and malignant neoplasms by mechanisms that remain uncertain. In this review, we explore the evidence supporting the hypothesis that free radicals and other reactive oxygen species (ROS) are an important mechanism by which asbestos mediates tissue damage. There appears to be at least two principal mechanisms by which asbestos can induce ROS production; one operates in cell-free systems and the other involves mediation by phagocytic cells. Asbestos and other synthetic mineral fibers can generate free radicals in cell-free systems containing atmospheric oxygen. In particular, the hydroxyl radical often appears to be involved, and the iron content of the fibers has an important role in the generation of this reactive radical. However, asbestos also appears to catalyze electron transfer reactions that do not require iron. Iron chelators either inhibit or augment asbestos-catalyzed generation of the hydroxyl radical and/or pathological changes, depending on the chelator and the nature of the asbestos sample used. The second principal mechanism for asbestos-induced ROS generation involves the activation of phagocytic cells. A variety of mineral fibers have been shown to augment the release of reactive oxygen intermediates from phagocytic cells such as neutrophils and alveolar macrophages. The molecular mechanisms involved are unclear but may involve incomplete phagocytosis with subsequent oxidant release, stimulation of the phospholipase C pathway, and/or IgG-fragment receptor activation. Reactive oxygen species are important mediators of asbestos-induced toxicity to a number of pulmonary cells including alveolar macrophages, epithelial cells, mesothelial cells, and endothelial cells. Reactive oxygen species may contribute to the well-known synergistic effects of asbestos and cigarette smoke on the lung, and the reasons for this synergy are discussed. We conclude that there is strong evidence supporting the premise that reactive oxygen species and/or free radicals contribute to asbestos-induced and cigarette smoke/asbestos-induced lung injury and that strategies aimed at reducing the oxidant stress on pulmonary cells may attenuate the deleterious effects of asbestos.

In plain English

This article was a review, not a new study. The authors gathered laboratory, animal and some human research on whether free radicals and related reactive oxygen species help explain how asbestos injures the lung. They described two main routes. In the first, reactions at the fiber surface form the hydroxyl radical, with fiber iron playing a role (about 27% iron in crocidolite and amosite, 2-6% in chrysotile). In the second, asbestos activates immune cells (alveolar macrophages and neutrophils) that release oxidants. Iron-binding chemicals either reduced or increased radical formation, depending on the chemical and on the asbestos sample used. The authors noted that some results were inconsistent, and that several studies detected no significant oxidant release from immune cells. They described a rat study in which polyethylene glycol-conjugated catalase lessened lung fibrosis from inhaled asbestos. In laboratory solutions containing EDTA and a spin trap, tar plus asbestos gave a hydroxyl radical signal three- to fourfold stronger than without asbestos. The authors concluded that free radicals are "important, probably critical" intermediates in asbestos-related damage.

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: Review of published (and some unpublished) laboratory, animal and human research
• Who was studied: Studies reviewed by the authors: cell-free chemical experiments, cultured cells (macrophages, neutrophils, lung epithelial cells, mesothelial cells, endothelial cells, fibroblasts), animal models, and a few studies of exposed workers or patients. No search method or study count is given; the article lists 212 references.
• Exposure: Asbestos fibers, including the amphiboles crocidolite and amosite and the serpentine fiber chrysotile, plus other mineral fibers. Cigarette smoke and tar, alone and combined with asbestos.
• Main results:
  • The authors described at least two main routes by which asbestos can cause radical production: one in cell-free systems and one through phagocytic (immune) cells.
  • Crocidolite and amosite each contain about 27% iron. Chrysotile has a lower iron content of 2-6%.
  • Iron-binding chemicals (chelators) either inhibited or increased asbestos-catalyzed hydroxyl radical generation and/or pathological changes, depending on the chelator and on the nature of the asbestos sample used.
  • Various mineral fibers triggered release of superoxide and hydrogen peroxide from alveolar macrophages and neutrophils (polymorphonuclear leukocytes) in the studies listed in Table 1.
  • Several studies did not detect significant oxidant release from phagocytic cells exposed to asbestos alone in the laboratory.
  • In a cited study of 18 patients with asbestosis, half had alveolar macrophages that spontaneously released more superoxide and hydrogen peroxide than normal alveolar macrophages.
  • In a cited rat inhalation model of asbestosis, polyethylene glycol (PEG)-conjugated catalase, but not PEG-conjugated SOD, lessened the severity and extent of the fibrotic lesions.
  • When a solution of cigarette tar plus asbestos was added to a solution containing EDTA and the spin trap, the hydroxyl radical signal was three- to fourfold stronger than in the absence of asbestos (work from the Louisiana State University group).
  • The authors reported that most authors of the epidemiological studies they reviewed found that the combined effect of asbestos and cigarette smoking on lung cancer is best explained as multiplicative.
• The authors' conclusion: The authors concluded that the evidence strongly supports free radicals as important, probably critical, intermediates in asbestos-related disease processes. They suggested that reducing oxidant stress in exposed lungs may help prevent the harmful effects of asbestos.
• Limitations the authors state:
  • Asbestos exposure can occur many years before disease appears, so the role of radicals is hard to establish.
  • Results on lipid peroxidation were not entirely consistent, partly because of weaknesses of the commonly used TBA assay.
  • Epidemiological studies of asbestos and smoking do not reveal the mechanism behind their interaction.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Pulmonary Fibrosis, Neoplasm, Reactive Oxygen Species (ROS), Mineral Fiber, Hydroxyl Radical, Alveolar Macrophage, Phagocytosis.

Related studies

• Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease — B.T. Mossman, J.P. Marsh (1989)
• Microsomal lipid peroxidation and oxy-radicals formation are induced by insoluble iron-containing minerals — M. Fontecave, M. Jaouen, et al. (1990)
• The role of oxygen free radicals in occupational and environmental lung diseases — V. Vallyathan, X. Shi (1997)
• Studies on the role of oxygen radicals in asbestos-induced cytopathology of cultured human lung mesothelial cells — E.W. Gabrielson, G.M. Rosen, et al. (1986)
• Cigarette smoke augments asbestos-induced alveolar epithelial cell injury: role of free radicals — D.W. Kamp, M.J. Greenberger, et al. (1998)
• Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals — A. Aljandali, H. Pollack, et al. (2001)

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