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KMID : 0350519930460030957
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Journal of Catholic Medical College
1993 Volume.46 No. 3 p.957 ~ p.965
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Effects of Captopril on Bleomycin Induced Pulmonary Toxicity in Mice
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Abstract
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Bleomycin, commonly used effective anticancer agents for various forms of cancer, is limited in it´s clinical usefulness due to a dose related pulmonary toxicity including interstitial pneumonitrs and pulmonary fibrosis. The mechanism underlying
this
drug induced pulmonary fibrosis is not fully understood as yet, but there are numerous evidences suggesting that the immune and inflammatory system affect the metabolic function on the primary connective tissue cell-fibroblast. Also there are
some
reports of steroid affecting fibroblast function and the steroid has been the most effective in bleomycin induced fibrotic response. Recently captopril has been reported to have anti-fibrotic, antiinflammatory and anti-oxidant activity. This
study
was
performed to evaluate the effects of captopril in bleomycin induced pulmonary toxicity in mice. Ninety mice were diveded into three groups ; Bleomycin group(control group) received only bleomycin, Captopil group received bleomycin in combination
with
captopril. Solumdrol group received bleomycin in combination with solumedrol. Bleomycin was administered intraperitoneally 8 mg/kg twice a week for 5 weeks to each group respectively. Captopril was adminstered in the feed at a regimen of 50 mg/kg
a
day
fo 5 weeks. Solumedrol was administered rntramuscularly 18 mg/kg a day for 5 weeks. The animals were sacrificed at 6 weeks later. As a index of pulmonary toxicity, morphometric analysis with light microscope was performed in lung tissuc stained
with
hematoxylin-eosin and Masson´s trichrome stains. The number of total pulmonary cell count, the percentage of consolidation of lung parcnchyma and the degree of fibrosis of lung parenchyma were measured.
@ES The results were as follows ;
@EN 1. In bleomycin group)control group), total pulmonary cell count was 23.30±4.35/10E-6㎡ and percentage of consolidation was 13.89±7.09%
2. In captolril group, total pulmonary cell count was 18.39±3.48/10E-8㎡ and percentage of consolidation was 9.79±4.80%, which were decreased significantly compared with control group(P<0.05).
3. In solumdrol group, total pulmonary cell count was 14.33±2.52/10E-8㎡ and percentage of consolidation was 5.72±3.28%, which were decreased significantly compared with control and captopril group(P<0.05).
4. There were no typical findings of pulmonary fibrosis in Masson´s trichrome stain, but early fibrotic changes were recognized in the portion of severe consolidation and alveloar septal thickening in some oleomycin group.
In conclusion, these results suggest that solumedrol inhibits the bleomycin induced pulmonary toxicity in mice and captopril shows less effective than solumdrol in it´s protective effect on bleomycin induced pulmonary toxicity.
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