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HERO ID
759099
Reference Type
Journal Article
Title
The role of cardiovascular disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation
Author(s)
Shannahan, J; Schladweiler, M; Padilla-Carlin, D; Nyska, A; Richards, J; Ghio, A; Gavett, S; Kodavanti, U
Year
2011
Is Peer Reviewed?
Yes
Journal
Inhalation Toxicology
ISSN:
0895-8378
EISSN:
1091-7691
Volume
23
Issue
3
Page Numbers
129-141
Language
English
PMID
21391781
DOI
10.3109/08958378.2011.551850
Web of Science Id
WOS:000288216600002
URL
http:///www.tandfonline.com
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Abstract
Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-overload and oxidative stress. Healthy male Wistar Kyoto (WKY), spontaneously hypertensive (SH) and SH heart failure (SHHF) rats were intratracheally instilled with 0.0, 0.25 or 1.0 mg/rat LA and examined at 1 day, 1 week or 1 month. Although histologically it was not possible to distinguish severity differences between strains in LA-induced initial inflammation and later fibrosis, quantitative assessment of biomarkers showed strain-related differences. LA-induced neutrophilic inflammation was reversible in WKY but persisted more in SH and SHHF. Lung MIP-2 mRNA increased only in WKY at 1 day in response to LA but not in SH and SHHF. Bronchoalveolar lavage fluid (BALF) protein increased in SH but not WKY at 1 week and 1 month, while γ-glutamyltransferase and N-acetyl-β-D-glucosaminidase activities increased in all strains (WKY>SH=SHHF). BALF ferritin levels were high at baseline and increased following LA exposure only in SH and SHHF. Ferritin heavy chain mRNA increased only in SHHF at 1 day. At 1 month ferritin light chain mRNA declined from already high baseline levels in SHHF but increased in WKY and SH suggesting its differential involvement in LA-induced injury in Fe-overload. Unlike WKY, both SHHF and SH failed to increase the lung lining antioxidant, ascorbate, in response to LA. We conclude that underlying CVD-associated Fe-overload is likely linked to persistent lung injury, inflammation and antioxidant decompensation following LA exposure in rats.
Keywords
Libby Amphibole; Iron; Inflammation
Tags
IRIS
•
Asbestos
•
Libby Amphibole Asbestos (Draft, 2011)
OPPT REs
•
OPPT_Asbestos, Part I: Chrysotile_A. Summary
Suggested Literature: Public Comments
•
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)
PubMed
Toxline
WoS
Legacy Uses
Health Outcomes
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