Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat

Bleomycin‐induced pulmonary fibrosis is known to be associated with the increased activity of two gelatinases, matrix metalloproteinase (MMP)‐2 and MMP‐9, in bronchoalveolar lavage (BAL). This study has investigated the effect of a synthetic inhibitor of MMP, batimastat, on the development of pulmon...

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Bibliographic Details
Published in:The Journal of pathology 2001-04, Vol.193 (4), p.538-545
Main Authors: Corbel, Marianne, Caulet-Maugendre, Sylvie, Germain, Noëlla, Molet, Sophie, Lagente, Vincent, Boichot, Elisabeth
Format: Article
Language:English
Subjects:
Animals
batimastat
Biological and medical sciences
Bleomycin
Body Weight - drug effects
Bronchoalveolar Lavage Fluid - cytology
Cell Count
collagen
fibrosis
Hydroxyproline - metabolism
lung
Male
matrix metalloproteinase
Matrix Metalloproteinase Inhibitors
Medical sciences
Metalloendopeptidases - metabolism
Mice
Mice, Inbred Strains
Pharmacology. Drug treatments
Phenylalanine - analogs & derivatives
Phenylalanine - therapeutic use
Protease Inhibitors - therapeutic use
Pulmonary Fibrosis - chemically induced
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - pathology
Pulmonary Fibrosis - prevention & control
Respiratory system
Survival Rate
Thiophenes - therapeutic use
TIMP
Tissue Inhibitor of Metalloproteinases - metabolism
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Summary:Bleomycin‐induced pulmonary fibrosis is known to be associated with the increased activity of two gelatinases, matrix metalloproteinase (MMP)‐2 and MMP‐9, in bronchoalveolar lavage (BAL). This study has investigated the effect of a synthetic inhibitor of MMP, batimastat, on the development of pulmonary fibrosis induced by bleomycin administration in mice. Animals wereintranasally instilled with saline or bleomycin (0.5 mg in 100 µl per mouse). Batimastat (30 mg/kg) or vehicle alone was administered by intraperitoneal injection 24 h and 1 h before saline or bleomycin instillation, and then daily at the same dosage until the end of the study. Fifteen days after bleomycin administration, BAL was performed and the lung was removed. Treatment of mice with batimastat significantly reduced bleomycin‐induced lung fibrosis, as shown in the lung by histopathological examination and by a decrease in hydroxyproline levels. Batimastat also prevented the increase in BAL macrophage and lymphocyte numbers, whereas it did not show any effect on the increased expression of active transforming growth factor‐beta (TGF‐β) in BAL. Batimastat treatment was effective in reducing MMP‐2 and MMP‐9 activity as well as the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) level in BAL. These results suggest that administration of the MMP inhibitor batimastat is useful in preventing experimental pulmonary fibrosis induced by bleomycin and raises the possibility of a therapeutic approach to human pulmonary fibrotic disease. Copyright © 2001 John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.826