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Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica.

Authors
Porter-DW; Millecchia-L; Robinson-VA; Hubbs-A; Willard-P; Pack-D; Ramsey-D; McLaurin-J; Khan-A; Landsittel-D; Teass-A; Castranova-V
Source
Am J Physiol, Lung Cell Mol Physiol 2002 Aug; 283(2):L485-L493
NIOSHTIC No.
20022831
Abstract
In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-B activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m3 silica, 6 h/day, 5 days/wk) for 116 days. We report time-dependent changes in 1) activation of alveolar macrophages and concomitant production of NO and ROS, 2) immunohistochemical localization of inducible NO synthase and the NO-induced damage product nitrotyrosine, 3) bronchoalveolar lavage fluid NOx and superoxide dismutase concentrations, and 4) lung lipid peroxidation levels. The major observations made in this study are as follows: 1) NO and ROS production and resultant damage increased during silica exposure, and 2) the sites of inducible NO synthase activation and NO-mediated damage are associated anatomically with pathological lesions in the lungs.
Keywords
Laboratory-animals; Animals; Animal-studies; Silica-dusts; Silicates; Inhalation-studies; Fibrosis; Pulmonary-system-disorders; Exposure-levels; Exposure-assessment; Lung-burden; Respiratory-system-disorders; Silicosis; Oxidation; Pulmonary-function; Pulmonary-system; Cytotoxicity; Cytotoxins; Aerosols; Author Keywords: silicosis; fibrosis; oxidant injury; nitrotyrosine
Contact
D.W. Porter, Pathology and Physiology Research Branch, Health Effects Laboratory Div., National Institute for Occupational Safety and Health, 1095 Willowdale Rd., M/S 2015, Morgantown, WV 26505
CODEN
APLPE7
CAS No.
14808-60-7; 10102-43-9
Publication Date
20020801
Document Type
Journal Article
Email Address
DPorter@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1040-0605
NIOSH Division
HELD; DART
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
OH; WV
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