N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers

Our plain-English summary of N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers, by F. Afaq, P. Abidi, Q. Rahman (Toxicology Letters, 2000).

The study

• Authors: F. Afaq, P. Abidi, Q. Rahman
• Journal: Toxicology Letters
• Published: 2000;117(1-2):53-60
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile, an important commercial variety of asbestos, is known to cause oxidative stress by enhancing production of hydrogen peroxide (H(2)O(2)) and thiobarbituric acid reactive substances (TBARS), depleting glutathione (GSH) and altering levels of GSH redox system enzymes. N-acetyl L-cysteine (NAC), a compound that increases GSH levels, protects cells against chrysotile toxicity. In the present study, rats were exposed intratracheally to a single dose (5 mg/rat) of chrysotile. This was followed by a daily dose of NAC 50 mg/kg. b. wt., i.p. At 1, 4, 8 and 16 days post chrysotile exposure lung lavage fluid was collected to determine H(2)O(2) generation, TBARS production, GSH level and its redox system enzymes activities. A significant decrease in H(2)O(2) and TBARS, an increase in GSH content and its redox system enzymes was observed in chrysotile+NAC animals in comparison to chrysotile-exposed animals. In this preliminary study it appears that NAC may be protecting cells against oxidative damage. This protection may be due to its ability to maintain intracellular GSH/oxidative scavenging capability.

In plain English

This was an animal experiment from the Industrial Toxicology Research Centre in Lucknow, India. It tested whether N-acetyl L-cysteine (NAC), a drug that raises levels of the antioxidant glutathione (GSH), reduced chemical stress in rat lungs caused by chrysotile asbestos. Female rats received saline, NAC alone, a single 5 mg dose of Indian chrysotile placed into the windpipe, or chrysotile plus daily NAC injections. Six animals per group were killed at 1, 4, 8 and 16 days, and their lung-wash fluid and lung immune cells (alveolar macrophages) were tested. Compared with chrysotile alone, rats given chrysotile plus NAC had less hydrogen peroxide on day 8 (22%) and day 16 (26%), less fat damage in cells on day 8 (24%) and day 16 (31%), and more GSH in cells on day 8 (32%) and day 16 (36%). These measures still differed from those of control rats. The authors described this as a preliminary study and concluded that NAC may protect cells against oxidative 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: Animal experiment (rats exposed in vivo, with treated and control groups)
• Who was studied: Female albino rats of the Druckery strain from the Industrial Toxicology Research Centre's breeding colony, Lucknow, India. They were split into four groups (saline control, NAC alone, chrysotile alone, chrysotile plus NAC), and six animals from each group were killed 1, 4, 8 and 16 days after exposure.
• Exposure: A single intratracheal dose of 5 mg per rat of Indian chrysotile mined at Cuddapah, followed by NAC at 50 mg per kg body weight daily by injection into the abdominal cavity
• Main results:
  • Chrysotile alone significantly increased the number of alveolar macrophages compared with control and NAC groups. Adding NAC to chrysotile produced a decrease in macrophage numbers that was not statistically significant.
  • In the chrysotile plus NAC group, hydrogen peroxide production by macrophages was significantly lower than with chrysotile alone on day 8 (22%) and day 16 (26%), but it remained elevated compared with controls.
  • Lipid peroxidation (a measure of fat damage) in the macrophage fraction of the chrysotile plus NAC group was significantly lower than with chrysotile alone on day 8 (24%) and day 16 (31%).
  • In the cell-free lung-wash fluid, lipid peroxidation in the chrysotile plus NAC group was significantly lower than with chrysotile alone only on day 16 (27%). Levels remained above control levels.
  • GSH content in macrophages of the chrysotile plus NAC group recovered significantly compared with chrysotile alone on day 8 (32%) and day 16 (36%).
  • In the lung-wash fluid, GSH recovery in the chrysotile plus NAC group was significant only on day 16 (34%). The authors noted that GSH depletion was still significant compared with controls.
  • Activity of the enzyme glutathione peroxidase in the chrysotile plus NAC group was significantly higher than with chrysotile alone on days 1, 4, 8 and 16, by 27, 40, 16 and 17% respectively.
  • Glutathione reductase activity in the chrysotile plus NAC group was higher than with chrysotile alone on day 1 (24%) and day 4 (27%). On days 8 and 16, NAC tended to prevent the rise in this enzyme seen with chrysotile.
• The authors' conclusion: The authors called this a preliminary study and concluded that NAC may be protecting cells against oxidative damage, possibly by maintaining intracellular GSH or scavenging oxidants.

Topics

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

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

Related studies

• 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)
• 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)
• 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)
• Augmentation of chrysotile-induced oxidative stress by BHA in mice lungs — I. Ahmad, K. Krishnamurthi, et al. (1995)
• Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells — V.L. Kinnula, K. Aalto, et al. (1994)
• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)

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