D-Penicillamine Prevents Collagen Accumulation in Lungs of Rats Given Bleomycin

Details

• Personal Author:
  Geismar LS ; Hennessey S ; Last JA ; Reiser KM
• Description:
  Pulmonary fibrosis is an end-stage response to various injuries. The clinical picture is one of diminished lung volumes, decreased lung compliance, and abnormal gas exchange, resulting ultimately in severe disability. There are many difficulties inherent in studying pulmonary fibrosis in humans. The initiating events may be unknown (as in some of the interstitial fibroses of unknown etiology), Even if a specific etiologic agent has been identified, it may be difficult to obtain accurate exposure data. The use of oxygen therapy and drugs early in the course of the disease, smoking, intercurrent disease, and genetic variability all serve to complicate evaluation of fibrogenesis. Study of the effects of pharmacologic intervention is equally difficult for the same reasons. In addition, it may not be possible to attempt intervention at the earliest stages of the disease. For these reasons we chose to use bleomycin-induced fibrosis in rats to investigate potential approaches to pharmacologic intervention. This animal model has been well-characterized histopathologically, and alterations in lung collagen content and types have been documented. In addition, several groups have used this model to evaluate agents for the treatment of pulmonary fibrosis. Such studies have generally focused on use of steroidal and nonsteroidal anti-inflammatory agents that presumably suppress the alveolitis that is believed to precede fibrosis. However, from a clinically pragmatic standpoint, one would like to be able to intervene after the fibrotic collagen is present in the lung. The obvious target for such an approach is the biosynthesis and extracellular metabolism of the collagen being produced by the injured lung. For example, Riley et al have prevented fibrosis in animal models by administering either proline analogues, which interfere with proper folding of collagen, or beta-aminopropionitrile, which interferes with collagen crosslinking. We also focused on intervention after the initiation of fibrosis by administering D-penicillamine to rats given bleomycin. Penicillamine has been shown to interfere with collagen crosslinking, presumably by reaction with the aldehyde crosslink precursors. High doses of penicillamine have been used to prevent the accumulation of collagen in hamster and rat models of pulmonary fibrosis. We decided to investigate the possibility of intervening in bleomycin-induced fibrosis with a dose of penicillamine similar to that used clinically in humans. In addition to measuring collagen accumulation in the lungs, we investigated the effects on collagen crosslinking, a potentially more sensitive index of clinical efficacy. [Description provided by NIOSH]
• Subjects:
  Animals Fibrosis Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Collagen Fibrils Lung Disorders Pulmonary Disorders Respiratory Diseases
• ISSN:
  0012-3692
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  89
• Issue:
  3
• NIOSHTIC Number:
  nn:20060325
• Citation:
  Chest 1986 Mar; 89(3)(Suppl):153S-154S
• CAS Registry Number:
  Bleomycin (CAS RN 11056-06-7)
• Federal Fiscal Year:
  1986
• Performing Organization:
  University of California Davis, Davis, California
• Peer Reviewed:
  True
• Start Date:
  19840928
• Source Full Name:
  Chest
• Supplement:
  Supplement
• End Date:
  19870831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:57c95c3b2e489c027fff5c9045c41f2675d677c6fac33e6e0e468fa465e4d65f1a6a6972016b4edf85ebe19172fda4c1bb82e5da9b03e30cbdf708c9d8e5ec55
• Download URL:
  https://stacks.cdc.gov/view/cdc/224267/cdc_224267_DS1.pdf
• File Type:
  [PDF - 370.34 KB ]