Use of Tetrandrine to Differentiate Between Mechanisms Involved in Silica-Versus Bleomycin-Induced Fibrosis

Details

• Personal Author:
  Barger MW ; Castranova, Vincent ; Hubbs, Ann F. ; Ma JKH ; Ma JYC ; Weber SL
• Description:
  Animals exposed to silica or bleomycin (BLM) develop pulmonary fibrosis. Tetrandrine (TT) has been shown to inhibit stimulant-induced macrophage respiratory burst and effectively reduce silica-induced lung injury. The present study employed TT as a probe to assess the differences in mechanisms involved in silica- and BLM-induced pulmonary responses. Rats received a single intratracheal instillation of silica (40 mg/rat, sacrificed 4 wk postexposure) or BLM (1 mg/kg or approximately 0.25 mg/rat, sacrificed up to 2 wk postexposure). TT was administered orally at 18 mg/kg, 3 times/wk for desired time periods beginning 5 d before silica or BLM exposure. Both the silica and BLM exposures resulted in a significant increase in lung weight, total protein, lactate dehydrogenase LDH), and phospholipids (PL) content in the acellular fluid from the first lavage, and hydroxyproline content in the lung tissue. Alveolar macrophages (AM) isolated from rats exposed to silica or BLM exhibited significant increases in secretion of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta (TGF-beta). TT treatment significantly lowered the silica- or BLM-induced increase in lung weight, while marginally reducing the release of IL-1 and TNF-alpha by AM. TT, however, markedly inhibited the silica-induced increase in the acellular protein, LDH and PL, hydroxyproline content, and the production of TGF-beta by AM but had no marked effect on these same parameters in BLM-exposed rats. Histological examination of rats exposed to BLM for 14 d showed pulmonary inflammation and fibrosis. TT treatment had only a small effect on limiting the extent of these lesions and did not significantly affect their severity. In summary, data indicate that many inflammatory and fibrotic effects of in vivo silica exposure are substantially attenuated by TT, whereas the stimulation by BLM is only marginally affected by this drug. Since TT acts to attenuate AM-mediated reactions, these results suggest that AM may play a pivotal role in silica-induced fibrotic development and may be less involved in the pathogenesis of BLM-induced fibrosis. [Description provided by NIOSH]
• Subjects:
  Laboratories Lung Diseases Neoplasms Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Carcinomas In Vitro Studies In Vivo Studies Laboratory Animals Pulmonary Cancer Pulmonary System Disorders
• ISSN:
  1528-7394
• 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:
  247-266
• Volume:
  57
• Issue:
  4
• NIOSHTIC Number:
  nn:20001012
• Citation:
  J Toxicol Environ Health A 1999 Jun; 57(4):247-266
• Contact Point Address:
  Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia
• CAS Registry Number:
  Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  1999
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ab6e1d1957fa0233c1d9b3ed21b42a0d38406e8536abf7a88ea692bf83d2db95677ed6e85d501aeb960c2125f10b98e49b252bf93644f0be692c1c6e9f2458a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/198294/cdc_198294_DS1.pdf
• File Type:
  [PDF - 255.49 KB ]