NIOSHTIC-2 Publications Search
Pulmonary oxidative stress, inflammation, and fibrosis induced by carbon nanotubes.
Kisin-E; Murray-AR; Johnson-V; Gorelik-O; Arepalli-S; Gandelsman-VZ; Hubbs-AF; Mercer-RR; Baron-P; Kagan-VE; Potapovich-AI; Castranova-V; Shvedova-AA
Shock 2005 Apr; 23(Suppl 2):65
Society is currently amidst a revolutionary development of remarkable new technologies based on novel applications of nanomaterials. From drug delivery tools and micro-circuitry elements to microcomputer networks and super-durable composite materials - this is just an illustration of the unprecendentedly broad range of applications and approaches using nanomaterials. One of the most interesting examples of nanoimaterials are carbon nanotubes (CNT), new members of carbon allotropes similar to fullerenes and graphite. Previously, we reported that exposure of human bronchial epithelial cells to CNT induced oxidative stress, depletion of antioxidants, morphological changes, cytotoxicity, and apoptosis. In the current study, we investigated pulmonary toxicity of CNT after pharyngeal aspiration by C57BLl6 mice. We found that CNT caused dose-dependent formation of granulomatous bronchointerstitial pneumonia, fibrosis (collagen accumulation), and changed pulmonary function. Administration of carbon nanotubes to C57BLl6 mice also resulted in a dose-dependent augmentation of biomarkers of inflammation quantified by bronchoalveolar lavage (BAL) cell counts, total protein, lactate dehydrogenase (LDH) and g-glutamyltranspeptidase (GGT) activities in BAL fluids and accumulation of pro-inflammatory and pro-fibrotic cytokines. CNT induced release of pro-inflammatory and pro-fibrotic cytokines from macrophages in vitro. Overall, our data suggest that exposure to CNT leads to pulmonary toxicity realized through synergized interactions of inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and fibrosis.
Respiratory-system-disorders; Pulmonary-system-disorders; Respirable-dust; Fibrosis; Nanotechnology
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