Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis

Our plain-English summary of Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis, by W.N. Rom, T. Harkin (Environmental Research, 1991).

The study

• Authors: W.N. Rom, T. Harkin
• Journal: Environmental Research
• Published: 1991;55(2):145-56
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, we hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA was measured in bronchoalveolar lavage and found to be similar to serum concentrations. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.

In plain English

This laboratory study tested whether dehydroepiandrosterone (DHEA), a hormone made by the adrenal glands, reduced the release of superoxide, an oxidant, by lung cells taken from people with asbestosis. The authors collected lung cells by bronchoalveolar lavage (lung washing) from 11 lifelong nonsmokers with asbestosis. These people had worked with asbestos for about 33 years as asbestos insulators, boilermakers and pipefitters. Fiber types were not named. In the dish, the cells released 32.4 nanomoles of superoxide (measured as cytochrome c reduced) per million cells per hour. The ethanol used to dissolve DHEA lowered this by itself to 23.5 (p less than 0.02). Adding DHEA at 10 to the power minus 4 molar lowered it further to 10.6 (p less than 0.02). Lower DHEA concentrations had smaller effects. DHEA measured in lavage fluid from eight other people ranged from 1 to 6 ng/dl. The authors noted that the effective concentrations were 530 to 5300 times natural lung levels. The authors concluded that DHEA may have a therapeutic role in reducing the oxidant burden in asbestosis, and they proposed testing it in an animal model. No patients were treated.

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 lung cells (mainly alveolar macrophages) recovered by bronchoalveolar lavage, with DHEA or ethanol vehicle added in the dish; plus measurement of natural DHEA levels in lavage fluid
• Who was studied: 11 lifelong nonsmoking asbestos workers with asbestosis. All had pleural changes on chest X-ray, all had shortness of breath on exertion, and 10 of 11 had rales. A separate group of eight people supplied lavage fluid for DHEA measurement: one normal, two with asbestosis, five with other lung disease. The authors were at Bellevue Hospital / New York University Medical Center. Recruitment place and dates are not stated.
• Exposure: Chronic occupational asbestos exposure, 33 plus or minus 2 years, as asbestos insulators, boilermakers and pipefitters; fiber types not specified. The laboratory exposure tested was DHEA dissolved in ethanol at 10 to the power minus 4, minus 5 and minus 6 molar.
• Main results:
  • Lavage cells from the 11 asbestosis subjects spontaneously released superoxide anion at 32.4 plus or minus 5.3 nmole cytochrome c reduced per million cells per hour, and hydrogen peroxide at 9.0 plus or minus 1.8 nmole per million cells per hour
  • The ethanol carrier alone reduced superoxide release from 32.4 plus or minus 5.3 to 23.5 plus or minus 4.8 nmole (p less than 0.02)
  • DHEA at 10 to the power minus 4 molar, in the same ethanol volume, reduced release further, from 23.5 plus or minus 4.8 to 10.6 plus or minus 1.6 nmole (p less than 0.02)
  • In dose-response tests, superoxide release was reduced by 63% at 10 to the power minus 4 molar DHEA, 43% at minus 5 and 37% at minus 6
  • Among the 11 subjects, the 7 with the highest superoxide release and the 4 with the lowest had similar years of asbestos exposure (34 versus 31). The high-release group included all 3 subjects with category 2/3 chest radiographs; the low-release four all had category 1.
  • DHEA in lavage fluid from the separate group of individuals ranged from 1 to 6 ng/dl
• The authors' conclusion: The authors concluded that DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis. They proposed testing it in an animal model.
• Limitations the authors state:
  • The authors observed that the ethanol solvent itself had a modest effect on oxidant release
  • The authors noted that the DHEA concentrations effective in the dish were far higher than those found naturally in lung lining fluid

Topics

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

Medical terms in this study, explained in our Lexicon: Superoxide, Alveolar Macrophage, Fibrosis, Bronchoalveolar Lavage (BAL).

Related studies

• Asbestos effects on superoxide production. An in vitro study of hamster alveolar macrophages — B.W. Case, M.P. Ip, et al. (1986)
• IgG specifically enhances chrysotile asbestos-stimulated superoxide anion production by the alveolar macrophage — R.K. Scheule, A. Holian (1989)
• Superoxide anion release by alveolar macrophages exposed to respirable industrial fibres: modifying effect of fibre opsonisation — K. Donaldson, I.M. Hill, et al. (1995)
• Brief inhalation of asbestos compromises superoxide production in cells from bronchoalveolar lavage — J.M. Petruska, J. Marsh, et al. (1990)
• Differential release of superoxide anions by macrophages treated with long and short fibre amosite asbestos is a consequence of differential affinity for opsonin — I.M. Hill, P.H. Beswick, et al. (1995)
• Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide — A. Cantin, F. Dubois, et al. (1988)

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