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Early and Delayed Effects of Naturally Occurring Asbestos on Serum Biomarkers of Inflammation and Metabolism
Citation:
Kodavanti, U., D. Andrews, M. Schladweiler, S. Gavett, D. Dodd, AND J. Cyphert. Early and Delayed Effects of Naturally Occurring Asbestos on Serum Biomarkers of Inflammation and Metabolism. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 77(17):1024-39, (2014).
Impact/Purpose:
Changes in circulating proteins were analysed in serum samples from intratracheal instillation study involving physicohemically different naturally occuring asbestos materials, and Libby amhibole inhalation study. The results from this study suggests that the lung injury induced by various types of asbestos materials may be associated with systemic acute-phase response and predisposition to insulin resistance and metabolic syndrome.
Description:
Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; a-2 macroglobulin, A2M; and a-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 um) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance.