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Examination of Susceptibility to Libby Amphibole Asbestos-Induced Injury in Rat Models of Cardiovascular Disease
Citation:
Shannahan, J., M. SCHLADWEILER, D. Carlin, J. E. RICHARDS, S. H. GAVETT, AND U. P. KODAVANTI. Examination of Susceptibility to Libby Amphibole Asbestos-Induced Injury in Rat Models of Cardiovascular Disease. Presented at Society of Toxicology 49th Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This Abstract compared susceptibility of 3 rat models of cardiovascular diseases to Libby amphibole asbestos and showed that baseline differences in gene expression pattern and underlymg pathology influence asbestos-indcued toxicity to the lung by showing reduced res onse in rats with preeistent disease.
Description:
Although cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects, no studies have been done assessing the influence of the disease on the development of lung injury induced by asbestos exposure. In this study we examined lung injury, oxidative stress and inflammation resulting from exposure to a ratrespirable fraction (PM2.5) of Libby amphibole (LA) asbestos. Healthy normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SH), and spontaneously hypertensive heart failure (SHHF) rats were exposed at 12 weeks of age to either saline (300 µ 1), or LA (0.25 or 1 mg/rat) by intratracheal instillation and analyzed at day-lor day-7 after exposure. Bronchoalveolar lavage fluid (BALF) was assessed for markers of pulmonary injury/inflammation. mRNA expression of inflammation and oxidative stress markers was analyzed in lung tissue by real-time RT-PCR. SH and SHHF rats had increased baseline vascular' leakage (protein) and neutrophils relative to WKY (SHHF>SH). Endpoints of both lung injury and inflammation demonstrated time and dose-dependent alterations; the response being greater at day-l post exposure. All strains responded to LA exposure at day-l by dose-dependent increases in γ-glutamyl transpeptidase, lactate dehydrogenase, and N-acetyl glucosaminidase in BALF. Interestingly, increased amounts of LA caused a decrease in the amount of protein present in the BALF of the SHHF at day-I. At day-7, protein levels for all treatment groups of SHHF were similar to control. LA induced a dose-dependent increase in gene expression of macrophage inflammatory protein-2 (MIP-2) day-l post-exposure in the WKY rat, but not in the other strains. Gene expression of heme-oxygenase-l (HO-l), a marker of oxidative stress, was slightly induced in WKY but reduced in SHHF rats at day-I. At day-7 post-exposure SH rats showed the greatest increase in HO-l while SHHF expression returned to baseline. We conclude that the underlying disease state of the SHHF rats paradoxically might impair their ability to mount a pulmonary inflammatory response to LA exposure that is comparable to the WKY and SH strains. Funding: EPAIUNC CR833237. This abstract does not reflect USEPA policy