Protective role of ascorbic acid against asbestos induced toxicity in rat lung: in vitro study

Our plain-English summary of Protective role of ascorbic acid against asbestos induced toxicity in rat lung: in vitro study, by S.G. Khan, S. Ali, Q. Rahman (Drug and Chemical Toxicology, 1990).

The study

• Authors: S.G. Khan, S. Ali, Q. Rahman
• Journal: Drug and Chemical Toxicology
• Published: 1990;13(2-3):249-56
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos fibers adsorb cytochrome P-450 and P-448 proteins from rat lung micosomal fractions and liberate heme from cytochrome P-448 on prolonged incubation in vitro. further, fibers, decrease the activities of benzo(a)pyrene hydroxylase and glutathione-S-transferase in microsomal and cytosolic fractions respectively. Mineral fibers also stimulate both the enzymatic (NADPH-induced) and non-enzymatic (Fe2(+)-induced) lipid peroxidation in microsomal fractions. Preincubation of microsomal and cytosolic fractions with a physiological concentration of ascorbic acid ameliorates, to a large extent, the changes induced by asbestos fibers.

In plain English

The authors injected female albino rats with 3-methylcholanthrene for four days, then killed them to obtain lung cell fractions (microsomes and cytosol), which were tested in vitro. Microsomes were exposed to UICC chrysotile or crocidolite asbestos (crocidolite only in the protein-binding and heme-release tests), and cytosol to chrysotile only, with or without ascorbic acid (vitamin C). Both fibers bound the proteins cytochrome P-450 and P-448 and, after prolonged incubation, released heme from P-448; ascorbic acid significantly reduced both effects. For example, chrysotile bound 16.50 picomoles of P-450 per mg of fiber without ascorbic acid and 6.43 with it. Chrysotile lowered benzo(a)pyrene hydroxylase activity from 40.30 to 21.15 picomoles of product per minute per mg of microsomal protein (35.4 with ascorbic acid). It cut glutathione-S-transferase activity by about 30%, from 225.8 to 160.0 nanomoles of product per minute per mg of cytosolic protein (205.6 with ascorbic acid). Ascorbic acid added before chrysotile significantly protected against lipid peroxidation (oxidative damage to fats); added afterward, it was less effective. The authors concluded that ascorbic acid may protect against asbestos-related changes in the lung.

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: In vitro laboratory experiment using lung subcellular fractions (microsomes and cytosol) from rats
• Who was studied: Lung microsomal and cytosolic fractions from female albino rats of the Industrial Toxicology Research Centre colony in Lucknow, India. The rats weighed 150 to 180 g and were injected with 3-methylcholanthrene (20 mg/kg body weight) intraperitoneally for four consecutive days, then killed to obtain the fractions. Table values are means of six experiments.
• Exposure: UICC standard reference chrysotile and crocidolite. The dose was 1 mg dust per mg protein for the microsomal adsorption and heme-release tests, which used both fibers. The enzyme and lipid peroxidation tests used 500 micrograms of chrysotile per mg protein. Ascorbic acid was used at 0.2 mM.
• Main results:
  • Ascorbic acid significantly reduced adsorption of cytochrome P-450 and P-448 by both fibers (p less than 0.001), measured in picomoles adsorbed per mg fiber. With chrysotile, P-450 went from 16.50 to 6.43 and P-448 from 26.91 to 11.04. With crocidolite, P-450 went from 12.30 to 4.39 and P-448 from 24.55 to 8.91.
  • Fibers liberated heme from cytochrome P-448 on prolonged (72-hour) incubation. Ascorbic acid reduced heme release (p less than 0.001), measured in picomoles heme released per mg fiber: from 11.77 to 4.86 with chrysotile, and from 7.78 to 2.79 with crocidolite.
  • Benzo(a)pyrene hydroxylase activity, in picomoles of 3-OH benzo(a)pyrene formed per minute per mg microsomal protein, was 40.30 in untreated microsomes and 21.15 with chrysotile. With ascorbic acid plus chrysotile it was 35.4, which was not significantly different from controls. Crocidolite was not tested for this enzyme.
  • Chrysotile reduced cytosolic glutathione-S-transferase activity by about 30%, from 225.8 to 160.0 nmole CDNB conjugates formed per minute per mg cytosolic protein (p less than 0.05). With ascorbic acid plus chrysotile it was 205.6, which was not significantly different from controls.
  • Ascorbic acid added before chrysotile gave significant protection against both NADPH-induced and iron-induced lipid peroxidation in microsomes. NADPH-induced peroxidation was 7.25 nmole malonaldehyde per mg protein with chrysotile and 1.12 with ascorbic acid added first. Adding ascorbic acid after the asbestos was less effective.
• The authors' conclusion: The authors concluded that their results suggest ascorbic acid may provide protection against asbestos-mediated alterations in lungs. They noted that experiments in living animals were in progress.

Topics

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

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Mineral Fiber.

Related studies

• Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung — Q. Rahman, S.G. Khan, et al. (1990)
• Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity — G. Martra, M. Tomatis, et al. (2003)
• 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)
• Garlic attenuates chrysotile-mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system — M. Ameen, M.S. Musthapa, et al. (2003)

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