Home LiteratureArticle Details
PMID: 86304 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin.

The American journal of pathology ·Vol. 95 ·No. 1 ·1979-04-00 ·Pages 117-30

Thrall RS, McCormick JR, Jack RM, McReynolds RA, Ward PA

Abstract

A model for pulmonary fibrosis in the rat has been developed using intratracheal administration of bleomycin. The histopathologic features of the reaction are similar to those reported in the hamster model. Increases in vascular permeability are seen in the lung within 24 hours and persist over a 2-month period. Extractable collagen, as measured by hydroxyproline, increases during this time by a factor greater than 1.5 times the reference control values of normal lung. During this same period, a prominent eosinophilia develops. The continued treatment of bleomycin-injected rats with indomethacin markedly diminishes the amount of extractable lung collagen at 60 days and the histopathologic evidence of pulmonary fibrosis. The eosinophilia over the first 3 weeks is also markedly suppressed. Less dramatic effects were seen with the permeability changes. These findings indicate that the rat is a reliable and useful model for the study of blemoycin-induced pulmonary fibrosis and that treatment with indomethacin ameliorates the lung changes.

MeSH Terms
Animals Bleomycin/pharmacology Capillary Permeability Collagen Cricetinae Eosinophils Indomethacin/pharmacology Leukocyte Count Lung/pathology Male Pulmonary Fibrosis/chemically induced Rats Rats, Inbred F344
Chemicals
Bleomycin Collagen Indomethacin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Thrall R S
McCormick J R
Jack R M
McReynolds R A
Ward P A
References (20)
20 references, click to expand
  1. Interstitial pulmonary fibrosis following busulfan therapy.
    Am J Med. 1961 Jul;31:134-9 PMID: 13730733
  2. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid.
    Arch Biochem Biophys. 1961 May;93:440-7 PMID: 13786180
  3. The principles of eosinophil diluents.
    Blood. 1952 May;7(5):550-4 PMID: 14925149
  4. Prostaglandin regulation of macrophage collagenase production.
    Proc Natl Acad Sci U S A. 1977 Nov;74(11):4955-8 PMID: 200941
  5. Fibroblast heterogeneity and prostaglandin regulation of subpopulations.
    Proc Natl Acad Sci U S A. 1977 Aug;74(8):3429-32 PMID: 269402
  6. Cyclic AMP and immune responses. II. Phosphodiesterase inhibitors as potentiators of polynucleotide effects on antibody formation.
    J Immunol. 1971 Oct;107(4):1036-42 PMID: 4106088
  7. The effects of a series of prostaglandins on in vitro models of the allergic response and cellular immunity.
    Prostaglandins. 1972 Dec;2(6):519-28 PMID: 4125844
  8. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice.
    Am J Pathol. 1974 Nov;77(2):185-97 PMID: 4141224
  9. Drugs which inhibit prostaglandin biosynthesis.
    Pharmacol Rev. 1974 Mar;26(1):33-67 PMID: 4208101
  10. Acute immunologic pulmonary alveolitis.
    J Clin Invest. 1974 Aug;54(2):349-57 PMID: 4277008
  11. Effects of serotonin, indomethacin and other antirheumatic drugs on the synthesis of collagen and other proteins in granulation tissue slices.
    Biochem Pharmacol. 1972 Nov 1;21(21):2835-40 PMID: 4539594
  12. Mechanism of eosinophilia. I. Factors affecting the eosinophil response of rats to Trichinella spiralis.
    J Exp Med. 1970 Jun 1;131(6):1271-87 PMID: 5419271
  13. Mechanism of eosinophilia. II. Role of the lymphocyte.
    J Exp Med. 1970 Jun 1;131(6):1288-305 PMID: 5419272
  14. Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung.
    J Pathol. 1971 Feb;103(2):123-9 PMID: 5567917
  15. Pathogenic mechanisms in pulmonary fibrosis: collagen-induced migration inhibition factor production and cytotoxicity mediated by lymphocytes.
    J Clin Invest. 1976 Nov;58(5):1223-32 PMID: 62760
  16. Bleomycin hypersensitivity pneumonitis.
    Ann Intern Med. 1978 Jan;88(1):47-9 PMID: 74226
  17. Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Lung volumes, volume-pressure relations, carbon monoxide uptake, and arterial blood gas studied.
    Am Rev Respir Dis. 1978 Feb;117(2):289-97 PMID: 76453
  18. Increased elastin and collagen content in the lungs of hamsters receiving an intratracheal injection of bleomycin.
    Am Rev Respir Dis. 1978 Feb;117(2):299-305 PMID: 76454
  19. Growth inhibition and morphological changes caused by indomethacin in fibroblasts in vitro.
    Exp Pathol (Jena). 1975;11(1-2):1-9 PMID: 786711
  20. Lymphokine stimulation of collagen accumulation.
    J Clin Invest. 1976 Jul;58(1):240-52 PMID: 932208
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1979-04-00
Pages
117-30
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC2042298
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]