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Inhalation of carbon nanotubes induces oxidative stress and cytokine response causing respiratory impairment and pulmonary fibrosis in mice.
Shvedova-AA; Kisin-E; Murray-AR; Johnson-V; Gorelik-O; Arepalli-S; Hubbs-AF; Mercer-RR; Stone-S; Frazer-D; Chen-T; Deye-G; Maynard-A; Baron-P; Mason-R; Kadiiska-M; Stadler-K; Mouithys-Mickalad-A; Castranova-V; Kagan-VE
Toxicologist 2008 Mar; 102(1):307
Due to their unique physico-chemical, electrical, mechanical and thermal properties, single walled carbon nanotubes (SWCNT) have numerous applications in electronics, aerospace devices, and computers, chemical, polymer and pharmaceutical industries. Previously, we have reported that pharyngeal exposure of C57BL/6 mice to SWCNT caused dose-dependent formation of granulomatous bronchial interstitial pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses and decrease in pulmonary function. In this study, we investigated whether whole-body inhalation exposure to aerosolized SWCNT (using generation system developed at NIOSH, Baron et al., 2007) caused pulmonary toxicity and early onset of fibrogenic response similar to adverse pulmonary toxicity reported previously. Here, we report that both inhalation and aspiration exposures to unrefined SWCNT (HiPco, CNI, Inc, TX) resulted in an augmentation of biomarkers of inflammation and oxidative stress as evidenced by ESR detection of POBN-spin trapped carbon centered radicals and significant depletion of antioxidants in mouse lungs, recruitment of inflammatory cells and increase in pro-inflammatory cytokines assessed in the bronchoalveolar lavage (BAL) fluid, and early onset of granulomatous lesions and interstitial pulmonary fibrosis. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and robust interstitial fibrosis.
Particulates; Particulate-dust; Cell-biology; Biological-factors; Biological-monitoring; Biological-effects; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Breathing; Inhalation-studies; Air-quality-measurement; Aerosol-sampling; Aerosol-particles; Fibrogenicity; Nanotechnology
Issue of Publication
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
WV; PA; OH; WA
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division