Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity

Our plain-English summary of Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity, by G. Martra, M. Tomatis, I. Fenoglio, et al (Chemical Research in Toxicology, 2003).

The study

• Authors: G. Martra, M. Tomatis, I. Fenoglio, S. Coluccia, B. Fubini
• Journal: Chemical Research in Toxicology
• Published: 2003;16(3):328-35
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Ascorbic acid is one of the major components of the antioxidants defenses of the lung lining layer where inhaled asbestos fibers are deposited. Crocidolite fibers were incubated at 37 degrees C in a 0.01 M aqueous solution of ascorbic acid for 25 days in order to investigate modifications in surface reactivity. Iron (820 nmol/mg) and monomeric silica (470 nmol/mg) were released in the supernatant, while ascorbic acid was consumed. The amount of iron and silicon released, respectively, 17 and 6% (in atoms) of the total fiber content, exceeded what was expected at the surface, suggesting a partial disgregation of crocidolite promoted by ascorbic acid. In the absence of ascorbic acid but at the same pH, the release of iron and monomeric silica was minimal. At time intervals, aliquots of fibers were withdrawn to evidence chemical modifications progressively taking place. Three families of Fe(II) centers, differing in coordinative unsaturation and progressively removed during incubation, have been evidenced from the FTIR spectra of NO adsorbed onto the fibers. The most uncoordinated ones are removed first. New highly uncoordinated iron sites are exposed at the fiber surface as a consequence of the erosion of the outmost layers while hydration of silica tetrahedra yields new silanol groups. The activity in the Fenton-like reaction (*OH from H(2)O(2)) decreases following surface iron depauperation. Conversely, the homolytic cleavage of the C-H bond (CO(2)*-) from the formate ion) appears related to the small fraction of iron ions always present but easily quenched by the adsorption of ascorbic acid or its oxidation products.

In plain English

This was a laboratory chemistry experiment on crocidolite asbestos fibers from a standard UICC batch. No people or animals were studied. The authors kept the fibers for 25 days at 37 °C in a solution of ascorbic acid (vitamin C), an antioxidant found in the fluid lining the lungs. For comparison, other fibers were kept in salt water alone at the same pH. In the ascorbic acid solution the fibers released 820 nmol of iron and 470 nmol of silicon per milligram of fibers, about 17% and 6% of their total iron and silicon. Release in salt water alone was minimal. All of the ascorbic acid was used up. The authors concluded that ascorbic acid partly dissolved the fibers. The fibers' ability to make hydroxyl radicals from hydrogen peroxide fell to about 10% of the original. A second radical-forming reaction, using formate, was reduced, but it largely returned when the fibers were heated before testing. The authors attributed this loss to ascorbic acid or its oxidation products sticking to active iron sites. The authors suggested that excess ascorbic acid in asbestos-exposed people may act as "a double sword". They also stated that their test conditions were far from those inside the 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 (cell-free, in vitro) chemistry experiment. Fibers were incubated in ascorbic acid solution and then studied by chemical analysis of the liquid, infrared spectroscopy with adsorbed NO, and EPR spin-trapping tests of free radical generation.
• Who was studied: Crocidolite asbestos fibers from a UICC (Union Internationale Contre le Cancer) batch used in the authors' earlier studies. No human or animal subjects. Laboratory at the University of Turin, Italy.
• Exposure: Crocidolite fibers (1 mg per mL) were kept for 25 days at 37 °C in 0.01 M sodium ascorbate plus 0.05 M NaCl. The control fibers were kept in 0.05 M NaCl, with pH adjusted with HCl to match. Fiber samples were withdrawn and tested after 5, 10 and 25 days.
• Main results:
  • Fibers in the ascorbic acid solution released 820 nmol of iron and 470 nmol of silicon per milligram of fibers over 25 days. This was 17% and 6% (in atoms) of the fibers' total iron and silicon.
  • Fibers in the salt-water control at the same pH released minimal iron and monomeric silica. Table 1 lists 23 µmol/g iron and 12 µmol/g monomeric silica, compared with 820 and 470 µmol/g in the ascorbic acid solution.
  • The ascorbic acid concentration fell steadily, and none was left in the fiber suspension at the end of the experiment.
  • The amounts released were too large to come from the fiber surface alone. The authors concluded that ascorbic acid partly dissolved the crocidolite fibers.
  • The specific surface area of the fibers rose from 8.0 to 9.5 square meters per gram. The authors read this as erosion of the fibers.
  • Infrared spectra showed surface iron sites being removed progressively during incubation. The least coordinated iron sites were removed most easily at first.
  • Hydroxyl radical generation from hydrogen peroxide fell to about 20% of the original fibers' yield after 5 days of incubation. From 10 days onward it fell to about 10%.
  • Carbon-centered radical release from formate was depleted after 5 days in fibers that were only dried after incubation. In fibers heated (outgassed at 400 °C) before testing, it fell to about 60% at 5 days and then recovered to the original value by 25 days.
  • The authors attributed the loss of formate-reaction activity mainly to adsorption of ascorbic acid molecules and/or their oxidation products on the active sites, which they described as "quenching". They described this as a strong suggestion, not a proof.
• The authors' conclusion: The authors concluded that ascorbic acid removes iron from crocidolite and attacks its silica framework. They suggested that in the lung this could use up antioxidant defenses, and that removed iron could produce damaging free radicals. In their view, excess ascorbic acid in people previously exposed to asbestos may promote, rather than prevent, the adverse reaction triggered by asbestos.
• Limitations the authors state:
  • The incubation conditions were far from physiological. The starting ascorbic acid concentration (0.01 M) was roughly ten thousand times higher than in bronchoalveolar lavage fluid (1.7 µM).
  • The incubation lasted far less time than asbestos persists in the body (decades).
  • The results do not represent how fast the process happens in the body, where many other substances compete for the fiber surface.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Surface Reactivity.

Related studies

• Protective role of ascorbic acid against asbestos induced toxicity in rat lung: in vitro study — S.G. Khan, S. Ali, et al. (1990)
• Selective ascorbate toxicity in malignant mesothelioma: a redox Trojan mechanism — E. Ranzato, S. Biffo, et al. (2011)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 2: Oxidant activity of the fibers — F. Turci, M. Tomatis, et al. (2005)
• High dose of ascorbic acid induces cell death in mesothelioma cells — Y. Takemura, M. Satoh, et al. (2010)
• Iron mobilization from asbestos by chelators and ascorbic acid — L.G. Lund, A.E. Aust (1990)
• Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos — G. Holtz, E. Bresnick (1988)

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