Effect of asbestos on the metabolism of vasoactive substances in isolated perfused guinea pig lungs

Our plain-English summary of Effect of asbestos on the metabolism of vasoactive substances in isolated perfused guinea pig lungs, by A. Cadieux, S. Massé, P. Sirois (Environmental Health Perspectives, 1983).

The study

• Authors: A. Cadieux, S. Massé, P. Sirois
• Journal: Environmental Health Perspectives
• Published: 1983;51:287-91
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The measurement of pulmonary metabolism of three vasoactive substances and quantitative assessment of changes in lung morphology were performed in a long-term study of asbestos-exposed guinea pigs. Animals received intratracheal injections of a single dose of a sterile suspension of Canadian chrysotile B (5 mg), while control animals received only saline. Six months after the treatment, the guinea pigs were sacrificed, the lungs removed, perfused via the pulmonary artery and the metabolism of vasoactive substances was assessed (in vitro) in a cascade superfusion system. At the end of the experiments, the lungs were fixed in a glutaraldehyde solution for microscopic examination. The tissue response consisted of both inflammatory reaction of terminal and respiratory bronchioles and diffuse alveolar septal infiltration with interstitial fibrosis. The reaction was characterized at six months by a progressive bronchiolitis obliterans with fibroblastic proliferation and collagen formation. The development of the disease did not cause significant changes in the metabolism of acetylcholine and bradykinin. However, the metabolism of prostaglandin E2 decreased with the appearance of the bronchiolitis obliterans. Our results showed that asbestos exposure may produce early biochemical changes resulting in altered lung metabolism of vasoactive substances; these modifications could contribute to the pathogenesis of asbestosis.

In plain English

This was an animal experiment. Guinea pigs received a single injection into the windpipe of 5 mg of Canadian chrysotile B asbestos. Control animals received only saline. Six months later the lungs were removed and a salt solution was pumped through their blood vessels. The researchers measured how much of three substances that act on blood vessels (bradykinin, acetylcholine and prostaglandin E2) the lungs removed, then examined the lungs under the microscope. Exposed lungs showed inflammation and scarring in and around the small airways, described as bronchiolitis obliterans. Removal of bradykinin (about 88%) and acetylcholine (about 82%) did not change. Removal of prostaglandin E2 fell from 83% in control lungs to 63% in exposed lungs (p less than 0.005), so about twice as much passed through the lungs. The authors concluded that asbestos may cause early chemical changes in the lung that could contribute to asbestosis. They said the physiological significance remained speculative. The article reports numbers of experiments but not the number of animals.

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: Animal experiment: asbestos-injected and saline-injected guinea pigs; at six months, isolated perfused lungs were tested in a bioassay (cascade superfusion system) and examined under the microscope
• Who was studied: Guinea pigs of either sex weighing 350 to 450 g, at the Université de Sherbrooke, Quebec, Canada. The number of animals is not stated. The table gives numbers of experiments per group: bradykinin 30 control and 21 asbestos; acetylcholine 11 control and 5 asbestos; prostaglandin E2 18 control and 20 asbestos.
• Exposure: A single intratracheal injection of a sterile suspension of Canadian chrysotile B (UICC), 5 mg per animal (0.25 mL of a 20 mg/mL suspension); controls received saline only. Lungs were studied six months after injection.
• Main results:
  • In chrysotile-exposed guinea pigs, the main lesions were in and around the terminal bronchioles: a granulomatous reaction around the bronchioles, areas of 'adenomatoid' appearance, and focal fibroblastic proliferation obstructing small airways (peribronchiolitis and bronchiolitis obliterans). The Results say these were seen in all exposed animals.
  • Removal of bradykinin by the lungs was unchanged: 87.9 plus or minus 1.86% (mean and SEM, 30 experiments) in controls versus 87.6 plus or minus 1.96% (21 experiments) in asbestos-exposed lungs.
  • Removal of acetylcholine by the lungs was unchanged: 82.4 plus or minus 2.7% (11 experiments) in controls versus 82.0 plus or minus 2.8% (5 experiments) in asbestos-exposed lungs.
  • Removal of prostaglandin E2 fell from 83% in controls (83.0 plus or minus 3.02%, 18 experiments) to 63% in asbestos-exposed lungs (63.6 plus or minus 5.2%, 20 experiments). The difference was statistically significant (p less than 0.005).
  • According to the authors, about twice as much prostaglandin E2 escaped the lungs in exposed animals: 37% of the injected dose, versus 17% in controls.
• The authors' conclusion: The authors concluded that asbestos exposure may produce early biochemical changes that alter how the lungs process vasoactive substances, and that these changes could contribute to the development of asbestosis. They suggested the drop in prostaglandin E2 removal could be due to inhibition of an enzyme (15-hydroxyprostaglandin dehydrogenase) or of the transport of prostaglandin E2 into cells.
• Limitations the authors state:
  • Injection into the windpipe spread the fibers unevenly, so the lung damage differed somewhat from one animal to another.
  • The authors stated that the physiological significance of the findings remained speculative.
  • The authors stated that how the lung injury interferes with prostaglandin E2 processing remained an open question requiring further study.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Interstitial Fibrosis, Collagen, Asbestos Exposure.

Related studies

• Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins — P. Sirois, G. Drapeau, et al. (1983)
• An adherent cell perifusion technique to study the overall and sequential response of rat alveolar macrophages to toxic substances — G. Forget, M.J. Lacroix, et al. (1983)
• Distribution of 6-6(n)-3[H]sucrose and its radiolabeled degradation products from isolated, perfused rat small intestine loops following prolonged ingestion of chrysotile asbestos — R. Jacobs, R.J. Richards (1980)
• Rapid short-term clearance of chrysotile compared with amosite asbestos in the guinea pig — A. Churg, J.L. Wright, et al. (1989)
• The ultrastructure of asbestos bodies from guinea-pig lungs — J.M. Davis (1964)
• Development of asbestos bodies on amosite, chrysotile and crocidolite fibres in guinea-pig lungs — S.K. Botham, P.F. Holt (1971)

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