Generation of hydroxyl radical by crocidolite asbestos is proportional to surface \[Fe3+\]

Our plain-English summary of Generation of hydroxyl radical by crocidolite asbestos is proportional to surface [Fe3+], by A.J. Ghio, J. Zhang, C.A. Piantadosi (Archives of Biochemistry and Biophysics, 1992).

The study

• Authors: A.J. Ghio, J. Zhang, C.A. Piantadosi
• Journal: Archives of Biochemistry and Biophysics
• Published: 1992;298(2):646-50
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Differences among fibrous silicates to effect injury in biological systems have been postulated to reflect oxidant generation by structural iron within the crystal lattice of amphiboles. Iron is also coordinated to the surface of all silicates in concentrations which depend on the density of acidic functional groups. We tested the hypothesis that oxidant generation by crocidolite is proportional to surface-complexed iron rather than variance in the lattice concentrations of this transition metal. Surface iron was quantified after its reduction to Fe2+ and chelation by citrate. Thiobarbituric acid (TBA) reactive products and dihydroxybenzoic acid products of salicylate were employed as indices of nonspecific oxidant and hydroxyl radical generation, respectively. Surface iron, TBA reactive products, and dihydroxybenzoic acid products all diminished after pretreatment of crocidolite with the metal chelator deferoxamine in concentrations varying from 0 to 250 mM. Inclusion of deferoxamine in the reaction mixture provided similar results of diminishing both TBA reactive products and dihydroxybenzoic acid generation. We conclude that oxidant generation by crocidolite is proportional to surface concentrations of iron which can be chelated using deferoxamine. The design of synthetic fibers without health effects after exposure will likely necessitate decreasing the number of surface acidic functional groups to diminish the capacity to complex iron (i.e., minimize the percentage SiO2).

In plain English

This was a laboratory test-tube study of crocidolite asbestos fibers. The authors tested whether the fibers' oxidant generation, including hydroxyl radical, depends on iron held on the fiber surface rather than iron inside the crystal. They treated crocidolite with the iron-binding drug deferoxamine at 0 to 250 mM. In one set of tests it was applied beforehand and then washed off; in another it was added to the reaction mixture. They then measured surface iron and two chemical markers of oxidant production. Pretreatment significantly reduced surface iron, though about 50% remained at 250 mM. Three repeated treatments reduced it further, but never to the levels found in water and buffer. Both oxidant markers fell as deferoxamine increased. With deferoxamine in the mixture, hydroxyl radical markers dropped to values approximating zero. Mean fiber diameter did not differ significantly between water-treated fibers and fibers treated with 250 mM deferoxamine. The authors concluded that oxidant generation by crocidolite is proportional to surface iron. They suggested that synthetic fibers designed to replace asbestos should have fewer surface acidic groups that bind iron. They cautioned that neither way of using deferoxamine can be assumed to reduce radical production inside a living body.

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) chemistry experiment on asbestos fibers; no people or animals were studied
• Who was studied: Samples of crocidolite asbestos fibers obtained from the National Institute of Environmental Sciences, Research Triangle Park, NC
• Exposure: Crocidolite at 1.0 mg/ml in reaction mixtures containing hydrogen peroxide and ascorbate. The fibers were either pretreated for 60 minutes with deferoxamine mesylate (0 to 250 mM) and then washed, or deferoxamine was added directly to the reaction mixture at 0 to 250 mM.
• Main results:
  • Mean fiber diameter did not differ significantly between crocidolite treated with water (1.97 plus or minus 0.57 microns) and with 250 mM deferoxamine (1.25 plus or minus 0.32 microns)
  • Pretreatment with deferoxamine significantly decreased surface iron on crocidolite, but at 250 mM about 50% of the iron was still detectable on the fiber
  • After three repeated 250 mM deferoxamine treatments, surface iron fell much further but never approached the iron levels in water and buffer
  • Nonspecific oxidant products (TBA-reactive products) fell with deferoxamine pretreatment. After three treatments at 250 mM, they did not differ significantly from the reaction without fibers.
  • Hydroxyl radical markers (dihydroxybenzoic acids) were suppressed by smaller deferoxamine concentrations than were needed to suppress the TBA-reactive products
  • Tests with hydroxyl radical scavengers (DMTU and DMSO) led the authors to conclude that the difference between the two markers was likely due to differences in assay sensitivity, not to a second type of radical
  • When deferoxamine was added to the reaction mixture instead of used as a pretreatment, hydroxyl radical markers diminished greatly. At all deferoxamine concentrations, hydroxyl radical production was reduced to values approximating zero.
  • Reaction mixtures without crocidolite also showed iron-dependent oxidant generation that decreased with deferoxamine
• The authors' conclusion: The authors concluded that oxidant generation by crocidolite is proportional to surface iron and can be diminished by chelating that iron with deferoxamine. They suggested that designing synthetic fibers without the health effects of asbestos will require reducing the surface acidic groups that bind iron.
• Limitations the authors state:
  • Neither pretreating the fibers with deferoxamine nor adding it to the mixture can be assumed to inhibit radical production in a living body
  • Mineral dusts can pick up iron from the body after entry, so pretreating fibers may not keep surface iron low
  • The therapeutic consequences of giving deferoxamine to people are not known, and the drug has a relatively narrow therapeutic range

Topics

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

Medical terms in this study, explained in our Lexicon: Hydroxyl Radical, Crocidolite, Silicate, Amphibole Group.

Related studies

• Asbestos catalyzes hydroxyl and superoxide radical generation from hydrogen peroxide — S.A. Weitzman, P. Graceffa (1984)
• Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica — I. Fenoglio, L. Prandi, et al. (2001)
• Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke — J.H. Jackson, I.U. Schraufstatter, et al. (1987)
• Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans — K.R. Maples, N.F. Johnson (1992)
• 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)
• Using yeast RNA as a probe for generation of hydroxyl radicals by earth materials — C.A. Cohn, R. Laffers, et al. (2006)

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