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Single-Walled Carbon Nanotubes Induce Pulmonary and Vascular Response Following Intratracheal Instillation
Citation:
SCHLADWEILER, M., J. H. SHANNAHAN, R. F. THOMAS, R. SAXENA, M. I. GILMOUR, AND U. P. KODAVANTI. Single-Walled Carbon Nanotubes Induce Pulmonary and Vascular Response Following Intratracheal Instillation. Presented at Annual Society of Toxicology meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This abstract characterizes the relationship between lung and vascular injury following intratracheal instillation of carbon nanotubes in rats. It demonstrates that single-walled carbon nanotubes caused mild pulmonary inflammation, oxidative stress and thrombosis gene expression in the lung but not in the aorta.
Description:
Carbon-based nanotubes have been shown to induce varying degrees of pulmonary response in rodents influenced by the dose, the extent of agglomeration, the chemistry of the suspension solution, and the functional properties. We hypothesized that low concentrations of non-modified or acid-functionalized (AF) single walled carbon nanotubes (SWCNT) will cause distinct pulmonary and aortic effects on markers of inflammation, coagulation, vasoconstriction and cell structural components following pulmonary exposure. Male Wistar Kyoto rats (12 week old) were intratracheally instilled with pre characterized freshly sonicated suspensions of SWCNT or AF-SWCNT at 0, 100 or 500 µg/kg in saline. Pulmonary injury and inflammatory effects were small as determined by bronchoalveolar lavage fluid (BALF) analysis and were generally concentration-dependent. Small increases in BALF protein were noted with high dose of both types of tubes (1-d>4-d) while small increases in albumin were noted with only AF-SWCNT at high concentration. Surprisingly, small but significant increases in BALF γ-glutamyl transferase activity (marker of cell membrane damage) were noted only with high concentrations of SWCNT but not AF-SWCNT. LDH activity was increased at high concentrations of both types of SWCNT at 4-d time point. Both types of nanotubes moderately increased BALF neutrophils at high concentration while no increase in macrophages occurred (1-d>4-d). Real-time PCR for mRNA markers of oxidative stress, inflammation, vasoconstriction, thrombosis and cell filamentous components in rats exposed to AF-SWCNT revealed pulmonary induction of HO-1, MIP-2, endothelin-1, PAI-1 and β-catenin at both time points (1-d>4-d). However, mRNA expression for any of the biomarkers was not altered in the aorta at either time points. Pulmonary instillation of SWCNT produces acute pulmonary inflammatory, vasoconstrictive and prothrombotic effects in rats, whereas these effects are not evident within 4 days in the aorta. (Does not reflect US EPA policy). Supported in part by EPA SEE Program, and EPA/UNC CR833237).