Chrysotile-mediated imbalance in the glutathione redox system in the development of pulmonary injury

Our plain-English summary of Chrysotile-mediated imbalance in the glutathione redox system in the development of pulmonary injury, by P. Abidi, F. Afaq, J.M. Arif, et al (Toxicology Letters, 1999).

The study

• Authors: P. Abidi, F. Afaq, J.M. Arif, M. Lohani, Q. Rahman
• Journal: Toxicology Letters
• Published: 1999;106(1):31-9
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A significant depletion in the content of glutathione (GSH) and alteration in GSH redox system enzymes were observed in the lung of chrysotile-exposed animals (5 mg) during different developmental stages of asbestosis. In the alveolar macrophages (AM) of exposed animals, the depletion in GSH started from day 1 and reached a maximum at day 16, whereas in lung tissue the maximum depletion was observed when fibrosis has matured. It appears that cellular GSH depletion triggers oxidative stress in the system as observed from increased thiobarbituric acid reactive substance (TBARS) production and alteration in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PD) and glutathione S-transferase (GST), the enzymes regulating oxidative tone. The depletion in GSH was also observed in red blood cells (RBC) of the exposed animals reaching a maximum when fibrosis matured. Thus the observed depletion in GSH, ascorbic acid and alteration in GSH redox system enzymes may be involved in fibrosis and carcinogenesis induced by chrysotile.

In plain English

In this animal experiment in Lucknow, India, female albino rats received a single 5 mg dose of Indian chrysotile asbestos into the windpipe, and control rats received saline. Groups of six were examined between 1 and 150 days later. The authors measured glutathione, a natural antioxidant, in lung-cleaning cells (alveolar macrophages), blood and lung tissue, and measured related enzymes in lung tissue. Macrophage glutathione fell by a maximum of 50% on day 16. Blood glutathione was significantly lower by 20% on day 16, 22% on day 30 and 28% on day 150. Lung glutathione fell from day 16, reaching 55% depletion on day 150, and ascorbic acid (vitamin C) fell by up to 40%. Three antioxidant enzymes became more active, glutathione S-transferase fell slightly, and lipid peroxidation, a marker of oxidative damage, rose in the lung throughout. Citing earlier work, the authors described day 150 as a stage of mature fibrosis. They concluded that falling glutathione may serve as an early indicator of lung disease, and that these changes may be involved in chrysotile-induced fibrosis and carcinogenesis.

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: Animal experiment: a single intratracheal dose of chrysotile in rats, compared with saline-treated controls at several time points
• Who was studied: Female albino rats from the Industrial Toxicology Research Centre breeding colony, Lucknow, India. Six exposed and six control animals were examined at each time point. A first set was examined at days 1, 4, 8 and 16 (lung lavage cells and blood). A second set was examined at days 1, 4, 8, 16, 30, 90 and 150 (lung tissue). The total number of animals is not stated.
• Exposure: Indian chrysotile asbestos from Cuddapah (Andhra Pradesh), given as a single intratracheal dose of 5 mg in 0.5 ml normal saline
• Main results:
  • Alveolar macrophages of exposed rats: glutathione fell gradually, with a maximum depletion of 50% on day 16
  • Blood of exposed rats: glutathione was significantly decreased by 20% on day 16, 22% on day 30 and 28% on day 150
  • Lung tissue (cytosolic fraction) of exposed rats: glutathione depletion began on day 16 and reached a maximum of 55% on day 150
  • Lung tissue of exposed rats: ascorbic acid depletion was significant from day 8 and reached a maximum of 40% on day 150
  • Lung tissue (cytosolic fraction) of exposed rats: activities of glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase increased significantly at all time periods
  • Glutathione peroxidase activity in exposed lungs peaked at 233% of control on day 90 and 229% of control on day 150
  • Glutathione reductase activity in exposed lungs was significantly increased at all time intervals, with a maximum of 203% on day 4
  • Glutathione S-transferase activity in exposed lungs was slightly decreased compared with controls throughout
  • Lipid peroxidation (TBARS production) in lung microsomes of exposed rats increased significantly throughout. It was highest from day 1 to day 8, decreased slightly, then rose again on day 150.
  • The authors described day 150 as a stage of mature fibrosis by citing earlier work (Arif, 1992), not by a measurement reported in this paper
• The authors' conclusion: The authors concluded that the decrease in cellular glutathione may serve as an early indicator of lung disease. They also concluded that the depletion of glutathione and ascorbic acid, together with the enzyme changes, may be involved in fibrosis and carcinogenesis induced by chrysotile.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Glutathione (GSH), Alveolar Macrophage, Fibrosis, Oxidative Stress, Carcinogenesis.

Related studies

• 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)
• N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers — F. Afaq, P. Abidi, et al. (2000)
• Chrysotile inhibits glutathione-dependent protection against the onset of lipid peroxidation in rat lung microsomes — J.M. Arif, I. Ahmad, et al. (1996)
• Glutathione release by pulmonary alveolar macrophages in response to particles in vitro — D.S. Boehme, K.R. Maples, et al. (1992)
• Effect of kerosene and its soot on the chrysotile-mediated toxicity to the rat alveolar macrophages — J.M. Arif, S.G. Khan, et al. (1997)
• Environmental contamination of chrysotile asbestos and its toxic effects on antioxidative system of Lemna gibba — A.K. Trivedi, I. Ahmad, et al. (2007)

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