Biochemical mechanisms in asbestos toxicity

Our plain-English summary of Biochemical mechanisms in asbestos toxicity, by Q. Rahman, B. Das, P.N. Viswanathan (Environmental Health Perspectives, 1983).

The study

• Authors: Q. Rahman, B. Das, P.N. Viswanathan
• Journal: Environmental Health Perspectives
• Published: 1983;51:299-303
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The alarming hazardous nature of asbestos makes it the foremost among toxic fugitive dusts. The biochemical mechanisms responsible for the diverse biological effects of asbestos, such as fibrosis, asbestos bodies, pleural plaques, respiratory difficulty, cancer, and cytotoxicity, are being studied in this laboratory. As asbestosis progresses in guinea pigs, along with reticulum formation, lysosomal enzymes are released from membrane-bound latent state to active free form, initiating degradative changes. Considerable alterations take place in the pulmonary metabolic machinery. Mitochondria in lung cells were found to be important loci for the toxic effect of asbestos. A profile of mitochondrial activity, in control and asbestotic animals, revealed specific enzymic changes such as increased cytochrome c oxidase during the disease. The functional organization of mitochondria was also altered, since the organelles from asbestotic lungs were swollen as measured by spectrophotometry. Glutamate dehydrogenase activity of mitochondria became exposed in asbestosis. The maleate dehydrogenase shunt which is involved in transport of the redox potential across the membrane was enhanced in cytosol and mitochondria. The involvement of microsomal enzymes in asbestosis was indicated by alterations in glucose-6-phosphatase and tyrosine transaminase and aniline hydroxylase. Changes in the biotransformational capacity of lung, due to asbestos, could be an important aspect in toxicity, especially the carcinogenic effect. Considerable alterations were encountered in the levels of different phospholipids and in mucopolysaccharide constituents. On the basis of the above, the molecular mechanisms in asbestos toxicity are explained as an integrated model. Interactions of dust constituents with those of membranes and the ensuing metabolic adjustments are thus important in the etiology of asbestosis.

In plain English

This article was the authors' summary of a series of earlier experiments from their own laboratory on how asbestos changes lung chemistry. Most of the work was in guinea pigs and some was in rats. In one guinea pig experiment, 40 mg of amosite dust was injected into the windpipe; other guinea pig experiments used amosite at unstated doses. As asbestosis developed, lung hydroxyproline and hexosamine rose, reflecting changes in collagen and mucopolysaccharides. Lysosomal enzymes, normally held inside membranes, were released in active form. In lung mitochondria, cytochrome c oxidase activity was higher in asbestotic lungs than in controls, ATPase activities fell, and the mitochondria were swollen. Microsomal glucose-6-phosphatase rose up to 150 days and later decreased. Lactic acid stayed significantly higher than in controls at 90, 150 and 210 days. Carbonic anhydrase activity was lower than in controls at 40, 80, 120 and 160 days. The authors concluded that fibrosis, pleural plaques, asbestos bodies, respiratory difficulty and cytotoxicity are related to asbestos damage to cell membranes. They added that early changes in asbestosis may have ramifications for asbestos-produced cancer. Animal numbers were not given.

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: Review by the authors of their own laboratory's earlier animal experiments
• Who was studied: Guinea pigs (most experiments) and rats (mitochondrial enzyme and swelling experiments), compared with control animals; numbers not given
• Exposure: Amosite asbestos dust. In the guinea pig fibrogenic-response experiment (Figure 1) the dose was 40 mg given intratracheally. Other guinea pig experiments (Figures 5 to 7) also used amosite injection but did not state the dose. The fiber type used in the rat experiments is not stated.
• Main results:
  • As asbestosis progressed, lung hydroxyproline and hexosamine contents increased, showing changes in collagen and mucopolysaccharides
  • In asbestotic lung, lysosomal enzymes lost their normal membrane-enclosed latency and were released in active form
  • In lung mitochondria, cytochrome c oxidase activity was higher in asbestotic lung than in controls at different stages
  • Calcium-activated and magnesium-activated ATPase activities in lung mitochondria were substantially decreased
  • Mitochondria from asbestotic lung were swollen, which the authors said could indicate altered permeability
  • Aconitase decreased and fumarase increased in asbestotic lung
  • In guinea pigs given amosite, microsomal glucose-6-phosphatase increased significantly up to 150 days and later decreased
  • Lung lactic acid was significantly higher than in controls at 90, 150 and 210 days after asbestos injection
  • Lactic dehydrogenase also increased, and the increase was due to the LDH5 isozyme
  • Carbonic anhydrase activity in guinea pig lung was lower than in controls at 40, 80, 120 and 160 days
• The authors' conclusion: The authors concluded that fibrosis, pleural plaques, asbestos bodies, respiratory difficulty and cytotoxicity are related to asbestos damage to biomembranes. They also concluded that early pathogenic changes in asbestosis may have ramifications for asbestos-produced cancer as well as toxicity.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibrosis, Asbestos Bodies, Pleural Plaques, Carcinogenic, Etiology.

Related studies

• Biochemical changes in guinea pig lungs due to amosite asbestos — V. Misra, Q. Rahman, et al. (1978)
• Interactions between magnetic nanowires and living cells: uptake, toxicity, and degradation — M. Safi, M. Yan, et al. (2011)
• Biochemical changes and pulmonary response of guinea pigs to asbestos dust — J. Singh, M.U. Beg, et al. (1976)
• Toxicity and carcinogenicity mechanisms of fibrous antigorite — V. Cardile, L. Lombardo, et al. (2007)
• Some biochemical effects of asbestos on macrophages — K. Miller, J.S. Harington (1972)
• Biochemical studies in infective amosite pneumoconiosis — A.K. Jaiswal (1981)

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