Chrysotile inhibits glutathione-dependent protection against the onset of lipid peroxidation in rat lung microsomes

Our plain-English summary of Chrysotile inhibits glutathione-dependent protection against the onset of lipid peroxidation in rat lung microsomes, by J.M. Arif, I. Ahmad, Q. Rahman (Pharmacology & Toxicology, 1996).

The study

• Authors: J.M. Arif, I. Ahmad, Q. Rahman
• Journal: Pharmacology & Toxicology
• Published: 1996;79(4):205-10
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The glutathione and vitamin E dependent protection of lipid peroxidation in an NADPH (0.4 mM) and chrysotile (500 micrograms/ml) containing system were investigated in vitro in rat lung microsomes. Addition of 1 mM glutathione to the above reaction system containing microsomes supplemented with vitamin E (1 nmol/mg protein) reduced lipid peroxidation. Similar protection by glutathione could be observed in normal unsupplemented microsomes though the degree of protection was less pronounced. Addition of free radical scavengers such as, superoxide dismutase (100 units/ml), catalase (150 units/ml), mannitol (1 mM) and beta-carotene (0.5 mM) to the reaction system showed an insignificant effect on lipid peroxidation. When the reaction was carried out in absence of glutathione, vitamin E content of peroxidizing microsomes decreased rapidly. In this system a concomitant increase in the activity of microsomal glutathione-S-transferase was observed which may serve as an alternative pathway to detoxify lipid peroxides. Addition of glutathione alone to the reaction system prevented both against the loss in vitamin E content and increase in the activity of glutathione-S-transferase. Supplementation of both vitamin E and glutathione was found to be effective in lowering glutathione-S-transferase activity to that of normal basal level. Our results suggest that chrysotile-mediated stimulation of NADPH-dependent lipid peroxidation may be due to hampering of glutathione-dependent protection which may ultimately exhaust membrane bound vitamin E. Our data further suggest that the lung tissue may have an inbuilt mechanism whereby glutathione-S-transferase may be triggered to cope with the excessive production of lipid peroxides.

In plain English

This was a laboratory (test-tube) study, not a study of people. The authors prepared microsomes, a fraction of cell membranes, from the lungs of female albino rats in India. They exposed them to UICC chrysotile asbestos at 500 micrograms per ml together with NADPH, a chemical that drives oxidation reactions. They measured lipid peroxidation (oxidative damage to membrane fats), vitamin E content, a glutathione-dependent vitamin E "regeneration factor", and the enzyme glutathione-S-transferase. Chrysotile alone moderately induced lipid peroxidation, and adding NADPH greatly enhanced it. Glutathione gave 49% protection in ordinary microsomes and about 76% in microsomes given extra vitamin E. The free radical scavengers tested gave insignificant protection in ordinary microsomes. Chrysotile significantly inhibited the regeneration factor. Vitamin E was generally used up except when glutathione was present. In microsomes without extra vitamin E, glutathione-S-transferase activity rose significantly during chrysotile-mediated peroxidation, and adding glutathione returned it to its basal level. The authors hypothesized that chrysotile with NADPH may deplete glutathione so that vitamin E cannot be regenerated, which may switch on glutathione-S-transferase as an alternative way to deal with excess lipid peroxides.

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 rat lung microsomes (cell membrane fractions); results are means of three replicates
• Who was studied: Lung microsomes from female albino rats (about 150 g) from the Industrial Toxicology Research Center animal colony, Lucknow, India; the number of rats is not reported
• Exposure: UICC chrysotile asbestos, fiber size below 30 micrometres, added at 500 micrograms per ml together with NADPH (0.4 mM) for 30 minutes at 37 degrees
• Main results:
  • Chrysotile alone moderately induced lipid peroxidation in the lung microsomes, and adding NADPH greatly enhanced it
  • Superoxide dismutase, catalase, mannitol and beta-carotene gave insignificant protection against lipid peroxidation in microsomes not supplemented with vitamin E
  • Glutathione (1 mM) gave 49% protection against lipid peroxidation in the unsupplemented chrysotile plus NADPH system
  • In vitamin E-supplemented microsomes, lipid peroxidation was significantly lower than in controls, and glutathione inhibited it by about 76%
  • Chrysotile significantly inhibited the glutathione-dependent vitamin E regeneration factor; with glutathione added, the factor stayed near basal level
  • Vitamin E in the microsomes was generally used up during NADPH- and chrysotile-induced lipid peroxidation, except in systems containing glutathione
  • Glutathione-S-transferase activity rose significantly during chrysotile-mediated lipid peroxidation in unsupplemented microsomes
  • Adding glutathione brought glutathione-S-transferase activity back to its basal level, more markedly in vitamin E-supplemented microsomes
• The authors' conclusion: The authors hypothesized that chrysotile- and NADPH-induced lipid peroxidation may be triggered partly by a ferrous-dioxygen complex as well as reactive oxygen species. They proposed that this may deplete glutathione so that vitamin E cannot be regenerated, which may activate microsomal glutathione-S-transferase as an alternative mechanism.
• Limitations the authors state:
  • The free radical scavengers were each tested at only one concentration, taken from published reports

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Glutathione (GSH), Superoxide.

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• Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung — Q. Rahman, S.G. Khan, et al. (1990)
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