Prevention of bleomycin-induced fibrosing alveolitis with indomethacin: stereological studies on rat lungs.
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 less than 0.001). In contrast, after combination with INDO significant differences to the control group could not be detected except for a slight increase of intra-alveolar macrophages (+62%). Thus, INDO is a highly efficient agent in the prevention of BLM-induced pulmonary damage.
Mall
G
G
Department of Pathology, University of Heidelberg, Federal Republic of Germany.
Zimmermann
P
P
Siemens
I
I
Burkhardt
A
A
Otto
H F
HF
D000818:Animals; D001761:Bleomycin; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats
D001761:Bleomycin; D007213:Indomethacin