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

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, the authors 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 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.

Authors:
;  [1]
  1. (New York Univ. Medical Center, New York (United States))
Publication Date:
OSTI Identifier:
6024379
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental Research; (United States); Journal Volume: 55:2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANTIOXIDANTS; BIOLOGICAL EFFECTS; ASBESTOS; HEALTH HAZARDS; IN VITRO; LAVAGE; LUNGS; MACROPHAGES; OCCUPATIONAL EXPOSURE; SUPEROXIDE RADICALS; ANIMAL CELLS; BODY; CONNECTIVE TISSUE CELLS; HAZARDS; ORGANS; PHAGOCYTES; RADICALS; RESPIRATORY SYSTEM; SOMATIC CELLS; 560300* - Chemicals Metabolism & Toxicology

Citation Formats

Rom, W.N., and Harkin, T.. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis. United States: N. p., 1991. Web. doi:10.1016/S0013-9351(05)80171-9.
Rom, W.N., & Harkin, T.. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis. United States. doi:10.1016/S0013-9351(05)80171-9.
Rom, W.N., and Harkin, T.. 1991. "Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis". United States. doi:10.1016/S0013-9351(05)80171-9.
@article{osti_6024379,
title = {Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis},
author = {Rom, W.N. and Harkin, T.},
abstractNote = {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, the authors 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 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.},
doi = {10.1016/S0013-9351(05)80171-9},
journal = {Environmental Research; (United States)},
number = ,
volume = 55:2,
place = {United States},
year = 1991,
month = 8
}
  • Inhaled asbestos induces accumulation of alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) in lung. Asbestos-enhanced production of superoxide anion (O-/sub 2/) by AM and/or PMN may be involved in the pathogenesis of asbestos-induced fibrosis, either through direct effects on collagen synthesis or via mediation of tissue injury and repair. In in vivo experiments, bronchoalveolar lavage (BAL) 3 to 8 weeks following intratracheal asbestos infections showed increases in both PMN and AM, with AM representing 78 to 82% of cells recovered. Inhalation models, generally regarded as more analogous to human exposures, have confirmed AM as the predominant component of the cellularmore » response to inhaled asbestos. In this study, the in vitro effects of asbestos fiber on O-/sub 2//sup -/ production by AM have been determined in cell populations derived from the Syrian golden hamster. AM for in vitro study were obtained by BAL. O-/sub 2//sup -/ production was monitored as superoxide dismutase (SOD) - inhibitable cytochrome c reduction. Significant rises in O-/sub 2//sup -/ release by AM were noted in the presence of 0.4 mg/ml crocidolite. Chrysotile induced levels of O-/sub 2//sup -/ release in AM which were similar to those evoked by crocidolite.« less
  • The potentiation of fatal bacterial pneumonia in mice by prior inhalation of ozone occurs at levels of this oxidant pollutant that are frequently present in ambient air. A likely mechanism for this effect is an ozone-induced inhibition in the ability of pulmonary alveolar macrophages (PAM) to produce superoxide anion radical (O2-) demonstrated in the present study. A 25% decrease in PAM O2- production, as measured by nitroblue tetrazolium reduction, occurred after exposure of Swiss-Webster mice to 0.11 ppm ozone for 3 h (p less than 0.05). After 1 ppm there was almost complete inhibition of O2- release. In contrast, themore » rat, which is highly resistant to the potentiation of bacterial infections by ozone, was less sensitive to inhibition of PAM O2- production, as measured by cytochrome c reduction (mouse IC50, 0.41 ppm; rat IC50, 3.0 ppm ozone for 3 h). The observed decrement in mouse PAM O2- production was not associated with any change in phagocytic ability, as measured by both latex bead ingestion and 51Cr-labeled sheep red blood cell ingestion. This decrease in O2- production in the presence of normal phagocytic activity is analogous to certain of the findings in the neutrophils of children with chronic granulomatous disease. A decrease in rat PAM membrane cytochrome b558 levels was observed after ozone exposure of 3 ppm for 3 h, preliminarily suggesting that the mechanism by which ozone interferes with PAM O2- production may be through interaction with this heme-containing electron carrier.« less
  • In vivo exposure of rats to ozone or nitrogen dioxide results in a dose-dependent increase in superoxide anion radical production (O/sub 2//sup -/.) by alveolar macrophages isolated from the exposed animals. When alveolar macrophages from ozone-exposed animals were stimulated with phorbol myristate acetate (PMA, a non-phagocytic stimulus of O/sub 2//sup -/. production) the decrease in O/sub 2//sup -/. production ranged from 85.9% of control at 3.2 ppm-hrs ozone to 7% of control at 10.5 ppm-hrs. In a similar fashion, O/sub 2//sup -/. production by PMA-stimulated macrophages from NO/sub 2/-exposed rats ranged from 78% of control at 18.3 ppm-hrs NO/sub 2/more » down to 14.5% of control at 51 ppm-hrs. Since the viability of the alveolar macrophages obtained from ozone or nitrogen dioxide exposed animals was 88% or better in all cases as judged by both Trypan blue exclusion and lactate dehydrogenase release, the decreased ability of these cells to produce superoxide anion radical cannot be attributed to a pollutant effect on cell viability. This diminution in superoxide anion radical production by alveolar macrophages from the pollutant-exposed animals might account, in part, for the ability of these 2 air pollutants to potentiate bacterial infections in laboratory animals.« less
  • Ethanol stimulates superoxide (O/sub 2//sup -/) production in rat alveolar macrophages. Increasing the ethanol concentration from 75 to 500 mM produces a linear dose response curve, generating between 10 and 30 pmol O/sub 2//sup -//min/10/sup 6/ cells. Thus, ethanol is a weak agonist of O/sub 2//sup -/ in these cells. Pretreatment with ethanol in the same concentration range results in a dose and time dependent inhibition of O/sub 2//sup -/ production by phorbol-12-myristate-13-acetate (PMA). 100 mM ethanol inhibits PMA (100 ng/ml)-induced O/sub 2//sup -/ production by 60% after 5 minutes and by 80% after 30 minutes of preincubation. At lowermore » concentrations (10-25 mM), however, ethanol causes a synergistic stimulation of PMA-induced O/sub 2//sup -/ production. Preincubation for 15 minutes with 10 mM ethanol results in a 20% increase in PMA-induced O/sub 2//sup -/ production. Synergism between PMA and ethanol is seen at ethanol concentrations which do not result in O/sub 2//sup -/ production by ethanol alone. This synergism is abolished by a 15 minute preincubation of the cells in EGTA. Thus, ethanol acts as a weak agonist for O/sub 2//sup -/ production and interacts significantly with PMA-induced stimulation of O/sub 2//sup -/ production.« less
  • Alveolar macrophages (AM) have been found to suffer significant functional deficits in response to nitrogen dioxide (NO[sub 2]) exposure. The present investigation examined changes in the activation of AM arachidonate metabolism and superoxide production in response to an environmentally relevant level of NO[sub 2]. Rats were exposed to 0.5 ppm NO[sub 2] for periods of 0.5-10 d and AM were obtained by bronchoalveolar lavage (BAL). NO[sub 2] exposure produced complex effects upon both unstimulated and stimulated AM arachidonate metabolism. Unstimulated AM synthesis of leukotriene B[sub 4] (LTB[sub 4]) was depressed rapidly within 1 d of exposure, and depressed again atmore » 5 d. Alveolar macrophage production of thromboxane B[sub 2] (TxB[sub 2]), LTB[sub 4], and 5-hydroxyeicosatetraenoate (5-HETE) in response to stimulation with the calcium ionophore, A23187, were acutely depressed within 1 d of exposure; however, generation of these compounds recovered to air-control levels with longer exposure, while 5-HETE was increased at 10 d. AM production of LTB[sub 4] in response to zymosan-activated rat serum (ZAS), was not depressed until following 5 d of exposure and remained slightly lower than air-control levels at 10 d. Levels of TxB[sub 2], LTB[sub 4], prostaglandin E[sub 2] (PGE[sub 2]), and prostaglandin F[sub 2[alpha]] (PGF[sub 2[alpha]]) measured in BAL fluid (BALF) were found to be depressed within 4 h of exposure, suggesting an acute decrease in the in vivo pulmonary arachidonate metabolism; however, production of these compounds generally recovered to air-control levels with longer exposure. The AM superoxide production stimulated by phorbol myristate acetate (PMA) was decreased rapidly and continuously throughout the study. Thus, exposure to a low concentration of NO[sub 2] acutely depresses activation of AM arachidonate metabolism and superoxide production in response to external stimuli, and may impede defense against pulmonary infection. 14 refs., 5 figs., 1 tab.« less