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Enhanced nitric oxide production associated with silica-induced disease in rats.

Authors
Castranova-V; Millecchia-L; Porter-DW; Robinson-VA; Willard-P; Hubbs-AF; Ramsey-D; McLaurin-J; Khan-A; Teass-A
Source
FASEB J 2002 Mar 16(5):A962
NIOSHTIC No.
20023062
Abstract
This study investigated the relationship between silica-induced lung damage, inflammation and fibrosis and nitric oxide (NO) production in rats exposed by inhalation to silica (15 mgim3 silica, 6 hr/day, 5 days/week, for 116 exposure days). Markers of pulmonary inflammation and damage rise rapidly (5-16 days of exposure) and are maintained at a relatively stable new set point through 40 days, before rising explosively at 79 and 116 days of exposure. Fibrosis is evident only during this explosive period of inflammation and damage. Silica inhalation results in a rapid (5 days) rise in NO-dependent chemiluminescence from alveolar macrophages (AM) NO products in bronchoalveolar lavage fluid increase significantly, exhibiting a time course similar to that for parameters of inflammation and damage. Immunohistochemical analysis of pulmonary inducible NO synthase (iNOS) and nitrotyrosine identified elevated iNOS and NO- induced damage in AM and type II cells after 79 days of exposure. This NO production is associated with glaucomatous regions of the lung These data indicate that NO production is associated temporally and anatomically with silica-induced lung disease in a rat inhalation model
Keywords
Silicates; Lung-disorders; Lung-function; Lung-irritants; Fibrosis; Animal-studies; Pulmonary-function; Pulmonary-system; Inhalation-studies; Laboratory-animals; Pulmonary-system-disorders; Respiratory-system-disorders
CODEN
FAJOEC
CAS No.
14808-60-7; 10102-43-9
Publication Date
20020322
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
5
ISSN
0892-6638
NIOSH Division
HELD; DART
Source Name
The FASEB Journal, Experimental Biology 2002, New Orleans, Louisiana, April 20-24, 2002
State
WV; OH
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