Dusts causing pneumoconiosis generate .OH and produce hemolysis by acting as Fenton catalysts

Our plain-English summary of Dusts causing pneumoconiosis generate .OH and produce hemolysis by acting as Fenton catalysts, by T.P. Kennedy, R. Dodson, N.V. Rao, et al (Archives of Biochemistry and Biophysics, 1989).

The study

• Authors: T.P. Kennedy, R. Dodson, N.V. Rao, H. Ky, C. Hopkins, M. Baser, E. Tolley, J.R. Hoidal
• Journal: Archives of Biochemistry and Biophysics
• Published: 1989;269(1):359-64
• Cited by: 84 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Silicates causing pneumoconiosis function as Fenton catalysts to generate hydroxyl radicals (.OH) when incubated with hydrogen peroxide and a reducing substance. In contrast, silicates which do not cause pneumoconiosis demonstrate no Fenton activity. Catalytic activity is decreased by pretreatment of silicates with the iron chelators deferoxamine or transferrin. Hemolysis from silicates is decreased by interventions which remove superoxide anion or hydrogen peroxide from the medium, or by pretreatment of dusts with iron chelators. Thus, asbestos and nonfibrous silicates may cause pneumoconiosis through a common oxidant mechanism by catalyzing production of toxic .OH radicals in the lung.

In plain English

This was a laboratory study of mineral dusts in test tubes and human red blood cells. No workers or animals were studied. The authors tested whether dusts act as Fenton catalysts, turning hydrogen peroxide into damaging hydroxyl radicals, a reaction in which iron or other metals take part. With ascorbate (vitamin C) present, amosite, chrysotile and crocidolite asbestos, Minusil-5 silica, kaolin and diatomite produced large amounts of hydroxyl radicals. The authors described these dusts as ones that cause pneumoconiosis. Without ascorbate, no dust was active. Pharmaceutical talc, wollastonite, nonfibrous tremolite and fiberglass showed little activity. Treating dusts with the iron-binding agents deferoxamine or transferrin reduced activity. At equal surface area, the asbestos types were equally active. The authors said surface iron may be responsible but did not rule out the crystal surface itself. Amosite, Minusil and kaolin increased a marker of cell-membrane damage and caused marked red cell bursting (hemolysis). Antioxidant and iron-binding treatments significantly reduced this hemolysis but did not completely prevent it. The authors concluded that pneumoconioses from fibrous and nonfibrous silicates may be another class of oxidant-mediated lung diseases.

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) experiments on mineral dusts, measuring hydroxyl radical generation in chemical reaction mixtures and damage to human red blood cells
• Who was studied: No people or animals; mineral dust samples tested chemically, and human red blood cells (erythrocytes) prepared from fresh whole blood of a single donor
• Exposure: Amosite, chrysotile (intermediate and short range) and crocidolite asbestos, nonfibrous tremolite, Minusil-5 silica, fiberglass, talc (USP), wollastonite, kaolin (noncalcined) and diatomite (flux-calcined); 1 mg per tube or 10 cm2 surface area for radical tests, 0 to 1.0 mg/ml for hemolysis tests (amosite, Minusil, kaolin)
• Main results:
  • With ascorbate, amosite, chrysotile and crocidolite asbestos, Minusil-5, kaolin and diatomite generated large quantities of hydroxyl radicals (measured as methane) from hydrogen peroxide
  • Without ascorbate, the silicates showed no catalytic activity
  • Pharmaceutical talc, wollastonite, nonfibrous tremolite and fiberglass showed little catalytic activity
  • Pretreating the silicates with the iron chelators deferoxamine or transferrin decreased Fenton activity
  • When normalized to 10 cm2 surface area, amosite, crocidolite and short and intermediate fiber chrysotile showed equivalent activity; the authors said this suggests a dependence on surface iron but does not rule out the crystal surface itself mediating electron exchange
  • Pretreating Minusil silica with aluminum lactate eliminated its ability to generate hydroxyl radicals
  • Amosite, Minusil and kaolin each increased malondialdehyde, a marker of membrane lipid peroxidation, in red cell suspensions (statistically significant, p less than 0.05, compared with red cells alone)
  • Amosite, Minusil and kaolin caused marked red cell lysis. This was significantly reduced by the anion channel blocker DIDS, by catalase, by iron-chelator pretreatment of the dusts, or by N-propyl gallate
  • Superoxide dismutase at 1000 U/ml reduced hemolysis (36 plus or minus 0.7% with 1 mg/ml amosite, 32 plus or minus 0.2% with 1 mg/ml Minusil, 21 plus or minus 1% with 1 mg/ml kaolin; p less than 0.001 compared with untreated), but not at lower concentrations
• The authors' conclusion: The authors concluded that fibrous and nonfibrous silicates may cause pneumoconiosis by a common oxidant mechanism, generating toxic hydroxyl radicals. They also concluded that these pneumoconioses may be another class of oxidant-mediated lung diseases
• Limitations the authors state:
  • The treatments did not completely prevent hemolysis. The authors suggest this might be due to inadequate scavenger concentrations, or to scavengers being excluded from the microenvironment at the cell membrane
  • The surface-area result suggests a role for surface iron but does not rule out that the crystal surface itself mediates the reaction

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Silicate, Hydroxyl Radical, Superoxide.

Related studies

• Interrelationship between hemolysis and lipid peroxidation of human erythrocytes induced by silicic acid and silicate dusts — S.V. Singh, Q. Rahman (1987)
• Asbestos catalyzes hydroxyl and superoxide radical generation from hydrogen peroxide — S.A. Weitzman, P. Graceffa (1984)
• Generation of hydroxyl radical by crocidolite asbestos is proportional to surface [Fe3+] — A.J. Ghio, J. Zhang, et al. (1992)
• Hydroxyl radical production in the presence of fibres by a Fenton-type reaction — M. Gulumian, J.A. van Wyk (1987)
• "Labrador lung": an unusual mixed dust pneumoconiosis — H.W. Edstrom, D.M. Rice (1982)
• The pulmonary response to fibrous dusts of diverse compositions — P. Gross, R.T. deTreville, et al. (1970)

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