Effect of Inhaled Crystalline Silica in a Rat Model: Time Course of Pulmonary Reactions

Details

• Personal Author:
  Castranova, Vincent ; Hubbs, Ann F. ; Ma JYC ; Millecchia L ; Porter, Dale ; Teass A
• Description:
  Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e. intratracheal instillation or a short duration inhalation exposure to a high dose of silica. Therefore, the question of pulmonary overload has been an issue in these studies. The objective of the current investigation was to monitor the time course of pulmonary reactions of rats exposed by inhalation to a non-overload level of crystalline silica. To accomplish this, rats were exposed to 15 mg/m3 silica, 6 h/day, 5 days/week for up to 116 days of exposure. At various times (5-116 days exposure), animals were sacrificed and silica lung burden, lung damage, inflammation, NF-KB activation, reactive oxygen species and nitric oxide production, cytokine production, alveolar type II epithelial cell activity, and fibrosis were monitored. Activation of NF-KB/DNA binding in BAL cells was evident after 5 days of silica inhalation and increased linearly with continued exposure. Parameters of pulmonary damage, inflammation and alveolar type II epithelial cell activity rapidly increased to a significantly elevated but stable new level through the first 41 days of exposure and increased at a steep rate thereafter. Pulmonary fibrosis was measurable only after this explosive rise in lung damage and inflammation, as was the steep increase in TNF-alpha and IL-1 production from BAL cells and the dramatic rise in lavageable alveolar macrophages. Indicators of oxidant stress and pulmonary production of nitric oxide exhibited a time course which was similar to that for lung damage and inflammation with the steep rise correlating with initiation of pulmonary fibrosis. Staining for iNOS and nitrotyrosine was localized in granulomatous regions of the lung and bronchial associated lymphoid tissue. Therefore, these data demonstrate that the generation of oxidants and nitric oxide, in particular, is temporally and anatomically associated with the development of lung damage, inflammation, granulomas and fibrosis. This suggests an important role for nitric oxide in the initiation of silicosis. [Description provided by NIOSH]
• Subjects:
  Animals Cytotoxins Fibrosis Laboratories Lung Lung Diseases Nitrogen Compounds Nitrogen Oxides Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Silicosis

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• Keywords:
  Animal-studies Animal Model Author Keywords: Silicosis Cytotoxicity Exposure-methods In-vitro-studies Laboratory-animals Lung-disease Lung-fibrosis Lung-function Nitric Oxide Nitrogen-compounds Nitrogen-oxides Pulmonary-disorders Pulmonary-function Pulmonary-system-disorders Reactive Oxygen Species Respiratory-system-disorders Silica-dusts

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• ISSN:
  0300-8177
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  177-184
• Volume:
  234
• Issue:
  1
• NIOSHTIC Number:
  nn:20022384
• Citation:
  Mol Cell Biochem 2002 May-Jun; 234-235(1-2):177-184
• Contact Point Address:
  National Institute for Occupational Safety and Health, Heath Effects Laboratory Division, MS L-2015, 1095 Willowdale Road, Morgantown, WV 26505, USA
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Molecular and Cellular Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f2700112e082671699b0f91539f32694811825d7e79d509d68a122898b85a9f4e31ece2bdf1e78a5e1d08123848fa1d7dbfedf7b2d46268cbda1316b2b2dca2b
• Download URL:
  https://stacks.cdc.gov/view/cdc/199181/cdc_199181_DS1.pdf
• File Type:
  [PDF - 156.67 KB ]