N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line

Our plain-English summary of N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line, by M. Zhang, H. Xia, M. Yu, et al (Toxicology in Vitro, 2018).

The study

• Authors: M. Zhang, H. Xia, M. Yu, L. Zhu, L. Ju, J. Chen, J. Zhao, Y. Xiao, K. Chen
• Journal: Toxicology in Vitro
• Published: 2018;53:200-207
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Man-made mineral fibres (MMMFs) such as glass wool (GW), rock wool (RW) and refractory ceramic fibres (RCFs) are widely used as substitutes of asbestos. The present study aimed to investigate the cytotoxic effects on human bronchial epithelial cells (BEAS-2B) exposed to GW1, RW1 and RCF2, considering their properties similar to that of asbestos. We assessed cell viability; cell morphological changes; apoptotic rate; DNA damage; reactive oxygen species (ROS) generation; activities of caspase-3, caspase-8 and caspase-9; and expression levels of FasL, phosphorylated p38, and total p38 MAPK proteins. N-acetyl-l-cysteine (NAC) was used as an ROS scavenger. We observed that MMMFs, especially RCF2, evidently changed cellular morphology, promoted DNA damage, and induced apoptosis. In addition, the cytotoxicities of MMMFs were dependent on ROS generation, and NAC could decrease their toxicity. Furthermore, our results showed that apoptosis induced by MMMFs was mediated by the mitochondrial apoptotic pathway and Fas death receptor pathway. Moreover, the p38 MAPK signalling pathway was also involved in the cytotoxicities of MMMFs. NAC exerts a protective effect against apoptosis and DNA damage induced by GW1, RW1 and RCF2. This study provides important implications for understanding the potential toxic effects of GW1, RW1 and RCF2 exposure; it also indicates that NAC may prevent respiratory diseases induced by exposure to MMMFs.

Copyright © 2018. Published by Elsevier Ltd.

In plain English

This was a laboratory study of cells grown in dishes, not a study of people. The authors exposed a commercial human bronchial (airway-lining) cell line, BEAS-2B, to three man-made mineral fibres used as asbestos substitutes: glass wool (GW1), rock wool (RW1) and refractory ceramic fibre (RCF2). Chrysotile asbestos served as a comparison. Some cells were first treated with N-acetylcysteine (NAC), an antioxidant. High fibre doses (100 or 200 micrograms per square centimetre) significantly reduced cell survival. At 20 micrograms per square centimetre for 48 hours, programmed cell death (apoptosis) was seen in 8.9% of RCF2-exposed cells, 7.8% of GW1-exposed cells and 6.8% of RW1-exposed cells. The figure was 11.6% with 10 micrograms per square centimetre of chrysotile. DNA damage rose with fibre dose but was lower than with chrysotile. RCF2 and GW1 significantly raised reactive oxygen species, which are damaging oxygen molecules. Pre-treatment with NAC reduced cell death, DNA damage and markers of cell-death pathways. The authors concluded that NAC protected these cells and may possibly prevent respiratory disease caused by these fibres.

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 on a human cell line
• Who was studied: BEAS-2B human bronchial epithelial cells (a commercial cell line); no human or animal subjects
• Exposure: Glass wool (GW1), rock wool (RW1) and refractory ceramic fibre (RCF2), with chrysotile (CH) asbestos as a positive control. Doses ranged from 5 to 200 micrograms per square centimetre for 48 hours. Most later tests used 20 micrograms per square centimetre of the man-made fibres and 10 micrograms per square centimetre of chrysotile. Some cells were pre-treated with 10 mM NAC.
• Main results:
  • At 100 or 200 micrograms per square centimetre, all tested fibres significantly reduced cell viability. At 20 micrograms per square centimetre, the man-made fibres caused less than 10% loss of viability.
  • Compared with GW1 and RW1, RCF2-treated cells had higher proportions of attached fibres, phagocytized (taken-up) fibres, and loss of microvilli (tiny projections on the cell surface).
  • The frequency of apoptotic cells after 48 hours was 8.9% with 20 micrograms per square centimetre of RCF2, 7.8% with GW1, 6.8% with RW1, and 11.6% with 10 micrograms per square centimetre of chrysotile.
  • NAC pre-treatment decreased the apoptotic level of cells exposed to RCF2, GW1, RW1 and chrysotile by 22.6%, 35.8%, 32.4% and 41.4%, respectively.
  • DNA damage, measured as mean tail moment in the comet assay, rose with dose for the man-made fibres but stayed lower than for chrysotile. RW1 caused no significant DNA damage at 5 micrograms per square centimetre.
  • NAC pre-treatment markedly reduced DNA damage, especially for GW1.
  • RCF2 and GW1 produced significantly higher levels of reactive oxygen species than untreated cells.
  • The man-made fibres raised the activities of caspase-3, -8 and -9 (enzymes involved in cell death) and the levels of FasL and phosphorylated p38 proteins. NAC reduced these increases.
• The authors' conclusion: The authors concluded that apoptosis and DNA damage caused by RCF2, GW1 and RW1 were mainly related to reactive oxygen species, fibre uptake and fibre adhesion. They also concluded that NAC protected the cells, suggesting that NAC may possibly prevent respiratory disease caused by exposure to man-made mineral fibres.
• Limitations the authors state:
  • Whether NAC affects DNA double-strand breaks caused by these fibres was not established and requires further study.
  • GW1 produced more reactive oxygen species than RCF2, even though RCF2 was more toxic in other tests. The authors described this as an apparent contradiction.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Reactive Oxygen Species (ROS), Apoptosis.

Related studies

• Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway — M. Zhang, J. Chen, et al. (2017)
• Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells — P. Nymark, K.A. Jensen, et al. (2014)
• Cytotoxic and oxidative effects induced by man-made vitreous fibers (MMVFs) in a human mesothelial cell line — D. Cavallo, A. Campopiano, et al. (2004)
• Role of PARP1 on DNA damage induced by mineral silicate chrysotile in bronchial epithelial and pleural mesothelial cells — M. Zhang, H. Xia, et al. (2021)
• Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves inactivation of Akt and MAPK pathways — A. Baldys, P. Pande, et al. (2007)
• Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres — G. Musumeci, V. Cardile, et al. (2011)

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