Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica.
In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-kappa 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/m(3) 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 NO(x) 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.
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505, USA. DPorter@cdc.gov
Dale W
DW
Porter
Lyndell
L
Millecchia
Victor A
VA
Robinson
Ann
A
Hubbs
Patsy
P
Willard
Donna
D
Pack
Dawn
D
Ramsey
Jeff
J
McLaurin
Amir
A
Khan
Douglas
D
Landsittel
Alexander
A
Teass
Vincent
V
Castranova
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007150:Immunohistochemistry; D008054:Lipid Peroxides / Q000378:metabolism; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000032:analysis; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D008054:Lipid Peroxides; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D012822:Silicon Dioxide; D015054:Zymosan; D013482:Superoxide Dismutase