The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes

Our plain-English summary of The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes, by M. Fontecave, D. Mansuy, M. Jaouen, et al (The Biochemical Journal, 1987).

The study

• Authors: M. Fontecave, D. Mansuy, M. Jaouen, H. Pezerat
• Journal: The Biochemical Journal
• Published: 1987;241(2):561-5
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Lipid peroxidation in rat liver microsomes induced by asbestos fibres, crocidolite and chrysotile, is greatly increased in the presence of NADPH, leading to malondialdehyde levels comparable with those induced by CCl4, a very strong inducer of lipid peroxidation. This synergic effect only occurs during the first minutes and could be explained by an increase or a regeneration of the ferrous active sites of asbestos by NADPH, which in turn could rapidly be prevented by the adsorption of microsomal proteins on the surface of the fibres. It is not inhibited by superoxide dismutase, catalase and mannitol, indicating that oxygen radicals are not involved in the reaction. It is also not inhibited by desferrioxamine, indicating that it is not due to a release of free iron ions in solution from the fibres. Lipid peroxidation in NADPH-supplemented microsomes is also greatly increased upon addition of magnetite. This could be linked to the presence of ferrous ions in this solid iron oxide, since the ferric oxides haematite and goethite are completely inactive.

In plain English

This was a laboratory experiment, not a study of people. The authors added asbestos fibres (crocidolite and Rhodesian A chrysotile) to liver microsomes, a cell-membrane preparation from rats pretreated with phenobarbital. They measured lipid peroxidation, a form of chemical damage to fats, by the amount of malondialdehyde (MDA) formed. When NADPH, a molecule that supplies electrons, was also present, 10 mg of crocidolite produced 5.49 plus or minus 0.45 nmol MDA per mg protein after 5 minutes. This compared with 0.42 with NADPH alone and 0.34 with crocidolite alone. Chrysotile was less active (2.02), and smaller amounts of crocidolite gave less MDA. The effect was strongest in the first 5 minutes. Superoxide dismutase, catalase and mannitol did not reduce it, and desferrioxamine did not reduce it during the first 5 minutes. Magnetite plus NADPH also raised MDA strongly, while the ferric oxides haematite and goethite did not. The authors concluded that the findings give a molecular basis for previously observed membrane damage by asbestos and could explain its proposed role as a tumour promoter.

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) biochemical experiment using rat liver microsomes
• Who was studied: Liver microsomes from male Sprague-Dawley rats pretreated with sodium phenobarbital. The number of rats is not stated. Each table value is the mean of four to ten observations (four to six for the iron oxide experiments).
• Exposure: Crocidolite and Rhodesian A chrysotile asbestos (1, 5 or 10 mg in a 1 ml incubation), with or without NADPH. Comparisons were made with carbon tetrachloride and with the iron oxides magnetite, haematite and goethite.
• Main results:
  • Crocidolite (10 mg) plus NADPH produced 5.49 plus or minus 0.45 nmol MDA per mg protein after 5 min. NADPH alone gave 0.42 plus or minus 0.15, crocidolite alone gave 0.34 plus or minus 0.10, and the control gave 0.
  • The combined effect of crocidolite and NADPH was efficient only during the first 5 minutes. The rate of lipid peroxidation then fell rapidly between 5 and 30 minutes.
  • The effect was dose-dependent. With NADPH, 1 mg of crocidolite gave 1.20 plus or minus 0.22 and 5 mg gave 2.68 plus or minus 0.32 nmol MDA per mg protein.
  • Chrysotile (10 mg) plus NADPH gave 2.02 plus or minus 0.21 nmol MDA per mg protein, less than crocidolite.
  • Carbon tetrachloride, described by the authors as one of the strongest known inducers of lipid peroxidation, gave MDA levels greater than but comparable with those seen with crocidolite.
  • Crocidolite preincubated with microsomes for 30 min gave only 0.85 plus or minus 0.25 nmol MDA per mg protein with NADPH.
  • Superoxide dismutase (5.56 plus or minus 0.80), catalase (5.50 plus or minus 0.50) and mannitol (5.45 plus or minus 0.45) did not reduce MDA from crocidolite plus NADPH (5.49 plus or minus 0.45).
  • Desferrioxamine did not change MDA production from crocidolite plus NADPH in the first 5 min (5.60 plus or minus 0.35). It stopped further MDA formation between 5 and 30 min.
  • Crocidolite increased the rate of NADPH oxidation in microsomes. This lasted only the first few minutes; after about 4 min the rate was roughly the same as without fibres.
  • With NADPH, magnetite gave 6.87 plus or minus 0.75 (5 mg) and 2.62 plus or minus 0.25 (1 mg) nmol MDA per mg protein, compared with 0.38 plus or minus 0.12 for NADPH alone. Haematite (0.31 plus or minus 0.15) and goethite (0.35 plus or minus 0.15) with NADPH had no effect.
• The authors' conclusion: The authors concluded that the ability of asbestos fibres, together with NADPH, to greatly increase microsomal lipid peroxidation gives a molecular basis for previously observed membrane damage by asbestos and could explain its proposed role as a tumour promoter. They also concluded that this oxidative stress could not be prevented by superoxide dismutase, catalase or iron chelators.
• Limitations the authors state:
  • The authors state that the nature of the active sites on the fibres that drive the reaction is not certain.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Chrysotile, Superoxide, Goethite.

Related studies

• Lipid peroxidation in microsomes induced by crocidolite fibres — M. Gulumian, F. Sardianos, et al. (1983)
• Crocidolite-induced lipid peroxidation in rat lung microsomes. I. Role of different ions — M. Gulumian, T.A. Kilroe-Smith (1987)
• Microsomal lipid peroxidation and oxy-radicals formation are induced by insoluble iron-containing minerals — M. Fontecave, M. Jaouen, et al. (1990)
• Chrysotile inhibits glutathione-dependent protection against the onset of lipid peroxidation in rat lung microsomes — J.M. Arif, I. Ahmad, et al. (1996)
• Effect of asbestos fibers on aryl hydrocarbon hydroxylase and aminopyrine N-demethylase activities of rat liver microsomes — C. Kandaswami, M. Rahimtula, et al. (1986)
• The role of catalytic iron in asbestos induced lipid peroxidation and DNA-strand breakage in C3H10T1/2 cells — C.J. Turver, R.C. Brown (1987)

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