Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers

Our plain-English summary of Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers, by V.A. Kostyuk, A.I. Potapovich, S.D. Speransky, et al (Free Radical Biology & Medicine, 1996).

The study

• Authors: V.A. Kostyuk, A.I. Potapovich, S.D. Speransky, G.T. Maslova
• Journal: Free Radical Biology & Medicine
• Published: 1996;21(4):487-93
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure of macrophages to asbestos fibers resulted in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation, and reducing peritoneal macrophages injury caused by asbestos. The concentrations pre-treatment of antioxidants that were required to prevent the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90 microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.-. These findings indicate that flavonoids are able to prevent the respiratory burst in rat peritoneal macrophages exposed to asbestos at the stage of activated oxygen species generation, mainly as superoxide scavengers. On the basis of this study it was concluded that natural flavonoids quercetin and rutin would be promising drug candidates for a prophylactic asbestos-induced disease.

In plain English

This was a laboratory experiment on cells, not a study of people. The authors took macrophages (a type of immune cell) from the abdominal cavity of Wistar rats and exposed them in test tubes to natural chrysotile asbestos fibers from Tuva, Russia, at 2 mg/ml. After 20 minutes nearly 100% of the cells were damaged, measured by release of the enzyme LDH. By comparison, 6 plus or minus 4% were damaged after exposure to titanium dioxide, which the authors described as a nonpathogenic (non-disease-causing) reference dust. Asbestos also increased oxygen-radical production and a marker of fat oxidation. Two plant compounds, quercetin and rutin, reduced these effects, and more compound gave more protection. The concentrations that cut cell damage by half were 90 micromolar for quercetin and 290 micromolar for rutin. Separate chemical tests showed that both compounds neutralised superoxide, a reactive form of oxygen. The compounds were tested only on isolated rat cells, rat liver microsomes (cell fragments) and chemical mixtures. The authors concluded that they would be promising drug candidates for preventing asbestosis. They also said further studies were needed to explain how the protection works.

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) experiment on isolated rat cells, with supporting tests in rat liver microsomes (a cell fraction) and in cell-free chemical model systems
• Who was studied: Peritoneal macrophages (immune cells from the abdominal cavity) isolated from Wistar rats, used at 2 × 10^6 cells/ml. The number of rats is not stated. Results are means of 3 to 6 experiments. Rat liver microsomes were also used in a separate lipid-peroxidation test.
• Exposure: Natural chrysotile asbestos fibers (5 to 10 micrometres) from Tuva, Russia, added at a final concentration of 2 mg/ml. Cells were treated with or without quercetin and rutin. Titanium dioxide particles were the reference dust.
• Main results:
  • Nearly 100% of macrophages were damaged (by LDH release) after 20 minutes at 2 mg/ml asbestos. At a lower concentration (printed as 'I mg/ml', apparently 1 mg/ml), 45 plus or minus 10% were damaged.
  • Only 6 plus or minus 4% of macrophages were damaged after 20 minutes with 2 mg/ml titanium dioxide, used as a reference nonpathogenic mineral dust.
  • The concentrations needed to reduce asbestos-caused cell injury by 50% were 90 micromolar for quercetin and 290 micromolar for rutin.
  • Quercetin and rutin cut oxygen-radical production (measured by chemiluminescence) from asbestos-exposed macrophages by 50% at 3 and 30 micromolar, respectively.
  • The flavonoids protected against formation of TBARS, a marker of lipid peroxidation, generally in a dose-dependent way.
  • In asbestos-exposed macrophages, the flavonoids were oxidized. The enzyme SOD inhibited quercetin oxidation by about 50% at most and inhibited rutin oxidation almost completely.
  • In a cell-free chemical system, quercetin and rutin inhibited superoxide-driven reduction of nitroblue tetrazolium by 50% at 5 and 15 micromolar, respectively.
  • In rat liver microsomes, quercetin and rutin inhibited carbon tetrachloride-dependent lipid peroxidation by 50% at 6 and 120 micromolar, respectively.
• The authors' conclusion: The authors concluded that quercetin and rutin protect rat peritoneal macrophages from asbestos injury, mainly by scavenging superoxide. They concluded that these natural flavonoids would be promising drug candidates for preventing asbestos-induced disease (asbestosis).
• Limitations the authors state:
  • The authors stated that further studies are needed to explain how the flavonoids protect macrophages from asbestos injury.
  • The authors questioned whether lipid peroxidation is the main cause of the cell injury. Quercetin fully blocked the lipid-peroxidation marker at concentrations where it only partly protected the cells.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, LDH Release, Superoxide.

Related studies

• Influence of metal ions on flavonoid protection against asbestos-induced cell injury — V.A. Kostyuk, A.I. Potapovich, et al. (2001)
• Antiradical and chelating effects in flavonoid protection against silica-induced cell injury — V.A. Kostyuk, A.I. Potapovich (1998)
• Effect of size of man-made and natural mineral fibers on chemiluminescent response in human monocyte-derived macrophages — M. Ohyama, T. Otake, et al. (2001)
• Enhancement of the macrophage oxidative burst by immunoglobulin coating of respirable fibers: fiber-specific differences between asbestos and man-made fibers — I.M. Hill, P.H. Beswick, et al. (1996)
• Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells — I.V. Kravchenko, V.A. Furalyov, et al. (2003)
• Cytotoxic effects of macrophages and asbestos on transformed rat mesothelial cells — V.A. Furalev, I.V. Kravchenko, et al. (2002)

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