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Pulmonary inflammatory and fibrotic responses in Fischer 344 rats after intratracheal instillation exposure to Libby amphibole
Citation:
Padilla-Carlin, D. J., M. SCHLADWEILER, J. Shannahan, U. P. KODAVANTI, A. Nyska, L. BURGOON, AND S. H. GAVETT. Pulmonary inflammatory and fibrotic responses in Fischer 344 rats after intratracheal instillation exposure to Libby amphibole. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 74(17):1111-32, (2011).
Impact/Purpose:
Pulmonary and histopathological changes examined up to 3 months after intratracheal instillation of rats with Libby amphibole and amosite asbestos showed significant inflammation and the beginning of fibrosis, especially after exposure to amosite
Description:
Increased incidences of asbestosis and mesothelioma have been reported in workers from Libby, Montana, associated with exposures to amphibole-contaminated vermiculite. In this study we investigated pulmonary and histopathological changes following Libby amphibole (LA) exposure in a rat model. Rat respirable fractions of LA and amosite (aerodynamic diameter < 2.5 um) were prepared by water elutriation. Male F344 rats were exposed to single doses of either saline (SAL), amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal instillation. At times from 1 d to 3 mo after exposure, bronchoalveolar lavage (BAL) was performed and right and left lungs were removed for RT-PCR and histopathological analysis, respectively. These data indicate that 0.65 mg amosite resulted in a higher degree of pulmonary injury, inflammation, and fibrotic events than LA at the same mass dose. Exposure to either amosite or high dose LA resulted in higher levels of cellular permeability and injury, inflammatory enzymes, and iron binding proteins in both BAL fluid and lung tissue at most time points when compared to SAL controls. However, mRNA expression for some growth factors (e.g., PDGF-A and TGF-1B), which contribute to fibrosis, were down-regulated at several time points. Furthermore, histopathological examination showed notable thickening of interstitial areas surrounding the alveolar ducts and terminal bronchioles. We conclude that a single pulmonary exposure to 0.65 mg of amosite or 6.5 mg LA in rats produced acute and persistent lung injury at least 3 mo after exposure.
