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Acute Phase Response and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure
Citation:
KODAVANTI, U. P., O. Alzate, J. Shannahan, D. L. ANDREWS, M. SCHLADWEILER, S. H. GAVETT, AND W. Winniik. Acute Phase Response and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
This Abstract examined the biomarkers of Libby amphibole exposure in rats. The data show that Libby amphibole induces acute phase response and markers of inflammation but not markers of metabolic syn drome.
Description:
Identification of biomarkers assists in the disease diagnosis and environmental health risk assessment. Exposure to Libby amphibole (LA) has been associated with increased cardiovascular mortality. We hypothesized that rats exposed to LA would present a unique serum proteomic profile which could help elucidate biomarkers of LA-induced injury. In a series of experiments (various LA exposure scenarios and time points) healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control), or LA. Several markers of cancer, inflammation, metabolic syndrome (MetS) and acute phase response (APR) were analyzed in serum. All rat strains exhibited acute increases in alpha-2-macroglobulin and α1-acid glycoprotein. Markers of inflammation, lipocalin-2 and osteopontin were increased in WKY rats after LA exposure while no LA effects were noted in the MetS markers adiponectin, insulin, leptin, or mesothelin. Quantitative Intact Proteomics profiling of WKY serum 1-day or 4-weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. These included circulating serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, and serum amyloid P, and decreased levels of serotransferrin, serum albumin, and fetuin A 1-day after LA exposure. All changes were evident at 1-day and/or 15-days but were reversible thereafter during recovery. Thus, our comprehensive analysis indicated that pulmonary exposure to LA induces an APR and novel biomarkers of inflammation that could be useful in understanding systemic health effects of asbestos. (This abstract does not represent US EPA policy).