Nitric Oxide and Reactive Oxygen Species Production Causes Progressive Damage in Rats After Cessation of Silica Inhalation

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• Personal Author:
  Beighley CM ; Brumbaugh K ; Castranova, Vincent ; Khan A ; McLaurin J ; Millecchia LL ; Porter DW ; Ramsey D ; Robinson VA ; Teass A ; Willard P
• Description:
  Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the relationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were exposed to silica (15 mg/m(3), 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were sacrificed at 0 days postexposure, while another portion was maintained without further exposure for 36 days to examine recovery or progression. The major findings of this study are: (1) silica-exposed rat lungs were in a state of oxidative stress, the severity of which increased during the postexposure period, (2) silica-exposed rats had significant increase in lung NO production which increased in magnitude during the postexposure period, and (3) the presence of silica particle(s) in an alveolar macrophage (AM) was highly associated with inducible nitric oxide synthase (iNOS) protein. These data indicate that, even after silica exposure has ended, and despite declining silica lung burden, silica-induced pulmonary NO and ROS production increases, thus producing a more severe oxidative stress. A quantitative association between silica and expression of iNOS protein in AMs was also determined, which adds to our previous observation that iNOS and NO-mediated damage are associated anatomically with silica-induced pathological lesions. Future studies will be needed to determine whether the progressive oxidative stress, and iNOS activation and NO production, is a direct result of silica lung burden or a consequence of silica-induced biochemical mediators. [Description provided by NIOSH]
• Subjects:
  Aerosols Aluminum Silicates Animals Cytotoxins Environmental Monitoring Fibrosis Laboratories Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal-studies Cytotoxicity Exposure-assessment Exposure-levels Inhalation-studies Laboratory-animals Lung-burden Oxidation Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-system-disorders Silica-dusts Silicates Silicosis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  188-197
• Volume:
  90
• Issue:
  1
• NIOSHTIC Number:
  nn:20029683
• Citation:
  Toxicol Sci 2006 Mar; 90(1):188-197
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2006
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dc24b177c814043ee4c7db9612496db7096ba6bf88216476205395c377cb4867e65128e7922c75cea04cb1d1b6ac464266ecb53ee5d94931648801ed2eae88b5
• Download URL:
  https://stacks.cdc.gov/view/cdc/190612/cdc_190612_DS1.pdf
• File Type:
  [PDF - 393.72 KB ]