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Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: Stereological studies on rat lungs

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Summary

The prevention of the pulmonary toxicity of bleomycin (BLM) has been investigated in experimental models where pulmonary damage was induced with one intra-tracheal dose of BLM. The present investigation was carried out as a pre-clinical study in which BLM was administered systemically. The non-steroid anti-inflammatory drug indomethacin (INDO) was chosen as a possible candidate for pulmonary protection. Twenty female Wistar rats were treated daily with 4 mg/kg (7.3 units) BLM intra-peritoneally for 50 days and 20 rats with BLM and with 1 mg/kg INDO subcutaneously for 62 days. There were 20 animals as controls. Histological examination revealed fibrosing alveolitis in the BLM-treated group which was markedly suppressed in the combination group. Quantitative morphological (stereological) parameters demonstrate that BLM induced alveolar wall thickening (+45%), pulmonary fibrosis (+110%), and an increase of alveolar wall nuclei and of intra-alveolar macrophages (volume densities +43% and +133%,P<0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intraalveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.

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Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    Gerhard Mall, Peter Zimmermann, Ingbert Siemens & Herwart F. Otto

  2. Department of Pathology, University of Bern, Bern, Switzerland

    Arne Burkhardt

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  1. Gerhard Mall
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  2. Peter Zimmermann
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  3. Ingbert Siemens
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  4. Arne Burkhardt
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  5. Herwart F. Otto
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Mall, G., Zimmermann, P., Siemens, I. et al. Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: Stereological studies on rat lungs. Vichows Archiv A Pathol Anat 419, 339–347 (1991). https://doi.org/10.1007/BF01606525

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  • DOI: https://doi.org/10.1007/BF01606525

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