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Single wall carbon nanotubes induce oxidative stress, acute inflammation, and progressive pulmonary fibrosis.

Kisin-E; Murray-AR; Castranova-V; Kagan-VE; Shvedova-AA
Toxicologist 2006 Mar; 90(1):318
Among different types of nano-particles, single-walled carbon nanotubes (SWCNT) with their unique electronic and mechanical properties may also exhibit unique biological interactions, thus necessitating studies of their health effects. Previously, we reported that exposure of human bronchial epithelial cells to SWCNT induced oxidative stress, depletion of antioxidants, morphological changes, and cytotoxicity. In the current study, we investigated pulmonary toxicity of SWCNT after pharyngeal aspiration by C57BL/6 mice. Administration of SWCNT to C57BL/6 mice resulted in a dose-dependent augmentation of biomarkers of cell injury and oxidative stress quantified by cell counts, total protein, lactate dehydrogenase and -glutamyltranspeptidase activities, as well as reduced levels of GSH and total antioxidant reserves along with the accumulation of lipid peroxidation products found in bronchoalveolar lavage (BAL) fluid and in the lung. Markers of pulmonary cytotoxicity were associated with early development of acute inflammation, collagen accumulation, and progressive fibrosis. Maximal increase of TGF-B in BAL fluid occurred on day 7 after the exposure of mice to SWCNT and corresponded to a peak of macrophage content as well as robust collagen formation and impaired pulmonary functions. Exposure to SWCNT in mice maintained on a vitamin E deficient diet significantly enhanced collagen deposition as compared to the vitamin E sufficient group. Overall, our data suggest that pharyngeal aspiration of SWCNT elicited a robust acute inflammatory response with early onset of progressive pulmonary fibrosis whose expression and severity was associated with the intensity of oxidative stress in the lung of the exposed C57BL/6 mice.
Laboratory-animals; Animals; Animal-studies; Fibrosis; Pulmonary-system-disorders; Cytotoxicity; Cytotoxins; Cytotoxic-effects; Biomarkers; Pulmonary-function; Exposure-levels; Exposure-assessment; Nanotechnology
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Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California