Experimental Study of the Pulmonary Toxicity of Combined Bleomycin and Captopril Administration in Mice

Kwon, Hack Doug; Shon, Tae Ik; Min, Kyung Shin

Abstract

Bleomycin is well recognized as an antineoplastic agent. Pulmonary toxicity is the most significant complication of bleomycin administration. The purpose of this study was to determine whether Captopril(an angiotensin converting enzyme inhibitor) can ameliorate pulmonary toxicity induced by bleomycin. Eighty mice were divided into two groups. The control group(n=40) received only bleomycin, and the other experimental group(n=40) received bleomycin in combination with captopril. Bleomycin was administered intraperitoneally to the mice, 8 mg/kg twice a week for 5 weeks. Captopril was administered in the feed at a regimen of 50 mg/kg everyday for 5 weeks. The animals were sacrified at 6 weeks later. Morphometric analysis with light microscopy was performed to the following parameters: the number of total pulmonary: cell count, percentage of consolidation of lung parenchyma and degree of fibrosis of lung parenchyma. The results were as follows; 1) In the control group, the number of total pulmonary cell count were 23.30+/-4.35/10(-8) m2 and the percentage of consolidation was 13.9+/-7.l%(P<0.01). 2) In the experimental group, the number of total pulmonary cell count were 18.39+/-3.48/10(-5) m2 and the percentage of consolidation was 9.8+/-4.8%(P<0.01). 3) There were no typical findings of pulmonary fibrosis in Massons trichrome stain, but early fibrotic change in the portion of severe consolidation and alveolar septal thickening in some control group. In conclusion, this study demonstrated that captopril ameliorates the pulmonary toxicity by bleomycin in the mice.