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Inhalation of carbon nanotubes induces oxidative stress and cytokine response causing respiratory impairment and pulmonary fibrosis in mice.

Authors
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
Source
Toxicologist 2008 Mar; 102(1):307
NIOSHTIC No.
20033629
Abstract
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.
Keywords
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
CAS No.
7440-44-0
Publication Date
20080301
Document Type
Abstract
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD; DART
Priority Area
Manufacturing
Source Name
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
State
WV; PA; OH; WA
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