Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species

Our plain-English summary of Prevention of asbestos-induced cell death in rat lung fibroblasts and alveolar macrophages by scavengers of active oxygen species, by M.A. Shatos, J.M. Doherty, J.P. Marsh, et al (Environmental Research, 1987).

The study

• Authors: M.A. Shatos, J.M. Doherty, J.P. Marsh, B.T. Mossman
• Journal: Environmental Research
• Published: 1987;44(1):103-16
• Cited by: 97 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cell injury and inflammation caused by asbestos are critical to the pathogenesis of pulmonary fibrosis (asbestosis). Our goal in studies here was to investigate the possible modulation of asbestos-related cell death using antioxidants in both target and effector cells of asbestosis. After exposure to crocidolite asbestos at a range of concentrations (2.5-25 micrograms/cm2 dish), the viability of a normal rat lung fibroblast line (RL-82) and freshly isolated alveolar macrophages (AM) was determined by exclusion of trypan blue and nigrosin, respectively. In comparison to fibroblasts, AM were more resistant to the cytotoxic effects of asbestos. Cytotoxic concentrations of asbestos then were added to both cell types in combination with the antioxidants, superoxide dismutase (SOD), a scavenger of superoxide (O2-.), and catalase, an enzyme scavenging H2O2. Dimethylthiourea (DMTU), a scavenger of the hydroxyl radical (OH.) and deferoxamine, an iron chelator, also were evaluated in similar studies. Results showed significant dosage-dependent reduction (P less than 0.001) of asbestos-associated cell death with all agents. In contrast, asbestos-induced toxicity was not ameliorated after addition of chemically inactivated SOD and catalase or bovine serum albumin. Results above suggest asbestos-induced cell damage is mediated by active oxygen species. In this regard, the iron associated with the fiber and/or its interaction with cell membranes might be critical in driving a modified Haber-Weiss (Fenton-type) reaction resulting in production of OH(.).

In plain English

This was a laboratory study in cells, not people or whole animals. The authors exposed two kinds of rat lung cells in culture dishes to crocidolite asbestos (a UICC reference sample) for 24 hours. One was a line of rat lung fibroblasts called RL-82. The other was alveolar macrophages freshly collected by washing out rat lungs. Asbestos killed cells in a dose-related way in both cell types, and the fibroblasts were more sensitive at higher amounts. At 15 micrograms of asbestos per square centimetre of dish, 48.3% of fibroblasts were alive. At 25 micrograms per square centimetre of dish, 63.4% of macrophages were alive. Several treatments reduced asbestos-related cell death in both cell types: the enzymes superoxide dismutase and catalase, dimethylthiourea, and pre-treating the fibers with the iron-binding drug deferoxamine. Inactivated enzymes and a plain protein (bovine serum albumin) did not. The authors concluded the results suggest asbestos-induced cell damage is mediated by active oxygen species. They noted the iron-based explanations did not account for the apparent importance of asbestos's fibrous nature, and that fiber-cell contact might also produce these species.

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 (in vitro) cell culture experiment
• Who was studied: Rat lung cells in culture: a diploid rat lung fibroblast line (RL-82) and alveolar macrophages freshly obtained from rats by bronchopulmonary lavage; studied at the University of Vermont College of Medicine. The number of animals is not given.
• Exposure: Crocidolite asbestos (UICC reference sample) at 2.5 to 25 micrograms per square centimetre of culture dish for 24 hours, alone or with superoxide dismutase, catalase, dimethylthiourea, deferoxamine-treated fibers, inactivated enzymes, or bovine serum albumin
• Main results:
  • Asbestos caused a dose-related decrease in viability in both fibroblasts and macrophages; fibroblasts were more sensitive at higher concentrations
  • Fibroblasts: 48.3% viable (mean, plus or minus 0.93) at 15 micrograms per square centimetre of dish, compared with 98.6% in untreated controls
  • Macrophages: 63.4% viable (mean, plus or minus 0.90) at 25 micrograms per square centimetre of dish, compared with 99.0% in untreated controls
  • Superoxide dismutase and catalase reduced asbestos cytotoxicity in both cell types (P less than 0.05) and did not affect untreated cells
  • Dimethylthiourea decreased asbestos cytotoxicity in both cell types
  • Fibers pre-treated with deferoxamine, an iron chelator, caused less cell death in both cell types
  • In fibroblasts exposed to 15 micrograms per square centimetre, viability increased linearly with the logarithm of each agent's concentration
  • Inactivated superoxide dismutase and catalase did not protect cells, and bovine serum albumin gave no significant prevention of cell death
• The authors' conclusion: The authors concluded that the results suggest asbestos-induced cell damage is mediated by active oxygen species.
• Limitations the authors state:
  • The authors noted that the iron-based explanations for how active oxygen species are generated do not account for the apparent importance of the fibrous nature of asbestos in cytotoxicity and disease, and suggested that direct fiber-cell interaction might also generate active oxygen species
  • The authors noted that chrysotile contains little iron, so other factors might be involved in cell damage by chrysotile

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Alveolar Macrophage, Inflammation, Pulmonary Fibrosis, Crocidolite, Superoxide, Hydroxyl Radical.

Related studies

• Scavengers of active oxygen species prevent cigarette smoke-induced asbestos fiber penetration in rat tracheal explants — A. Churg, J. Hobson, et al. (1989)
• Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells — J. Hobson, J.L. Wright, et al. (1990)
• Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease — B.T. Mossman, J.P. Marsh (1989)
• Approaches to prevention of asbestos-induced lung disease using polyethylene glycol (PEG)-conjugated catalase — B.T. Mossman, J.P. Marsh, et al. (1986)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Implication of active oxygen species as second messengers of asbestos toxicity — B.T. Mossman, J.P. Marsh, et al. (1987)

Browse more research in Environmental Research, or return to medical research.