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HERO ID
3089544
Reference Type
Journal Article
Subtype
Abstract
Title
Pulmonary toxicity and modifications in iron homeostasis following Libby amphibole asbestos exposure in rat models of cardiovascular disease
Author(s)
Shannahan, JH; Schladweiler, MCJ; Padilla-Carlin, DJ; Richards, JH; Gavett, SH; Kodavanti, UP
Year
2010
Is Peer Reviewed?
Yes
Journal
American Journal of Respiratory and Critical Care Medicine
ISSN:
1073-449X
EISSN:
1535-4970
Volume
181
Page Numbers
A1748
Language
English
DOI
10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A1748
Web of Science Id
WOS:000208771000748
Relationship(s)
is part of a larger document
3452678
Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Abstract
Rationale: Individuals suffering from cardiovascular disease (CVD) develop iron dysregulation which may influence pulmonary toxicity and injury upon exposure to asbestos. We hypothesized spontaneously hypertensive (SH) and spontaneously hypertensive heart failure (SHHF) rats would exhibit increased pulmonary injury and alterations in iron-homeostasis upon exposure to Libby amphibole (LA) asbestos compared to normotensive Wistar Kyoto (WKY) rats.
Methods: WKY (n=12/group), SH (n=6/group), and SHHF (n=6/group) were exposed at 12wks of age to either saline (300μl), or a rat-respirable fraction of LA (0.25 or 1 mg/rat) by intratracheal instillation and analyzed at day-1, day-7, or 1-month post-exposure. Bronchoalveolar lavage fluid (BALF) and lung mRNA expression for markers of iron homeostasis, oxidative stress and inflammation were analyzed.
Results: Total lavageable cells were higher in unexposed SH and SHHF relative to WKY (SHHF>SH). Total cell counts did not change in WKY but did increase in SH and HF at day-1, and 7. BALF protein increased in WKY and SH at day-1 and day-7 but decreased in SHHF at day-1, and remained elevated at 1-month in SH and SHHF exposed to 1 mg LA. All strains responded to LA with increased γ-glutamyl transferase, lactate dehydrogenase, and N-acetyl glucosaminidase in BALF at day-1 through 1-month. BALF ferritin was high at base line, and progressively increased at all times in SH and SHHF but not in WKY. Baseline BALF transferrin concentrations were high in SH and SHHF relative to WKY and further increased at day-7, in WKY and SH. Transferrin remained elevated in SH exposed to 1 mg at 1-month. mRNA expressions for oxidative stress and inflammatory proteins were higher at baseline in SH and SHHF compared to WKY. LA induced an increase in macrophage inflammatory protein-2 (MIP-2) at day-1 in WKY, but not in other strains. Gene expression of heme-oxygenase-1 (HO-1), an oxidative stress marker, was induced in WKY day-1 and SH at day-7 with no effect on SHHF. Growth factors PDGFA and B mRNA levels were similar in all strains at baseline and reduced in WKY and SHHF following exposure.
Conclusion: These results suggest that the underlying disease state of the SHHF might impair its ability to mount a pulmonary compensatory response to LA exposure that is comparable to the WKY and SH. Underlying pulmonary complications secondary to CVD and the ability to sequester iron by ferritin might play a role in modulating LA injury.
Funding: EPA/UNC CR833237. This abstract does not reflect USEPA policy.
Conference Name
American Thoracic Society 2010 International Conference
Conference Location
New Orleans, LA
Conference Dates
May 14-19, 2010
Tags
OPPT REs
•
OPPT_Asbestos, Part I: Chrysotile_F. Human Health
Total – title/abstract screening
On topic
Peer review
Primary source
Other forms of asbestos
•
OPPT_Asbestos, Part I: Chrysotile_Supplemental Search
LitSearch: Sept 2020 (Undated)
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