The Radioprotective Effect and Mechanism of Captopril on Radiation Induced Lung Damage in Rat / 대한방사선종양학회지

ABSTRACT

PURPOSE: It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We performed this study to investigate the radioprotective effect and mechanism of Captopril. METHODS AND MATERIALS The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains (TNFalpha and TGFbeta1) at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. RESULT: In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the TNFalpha expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the TGFbeta1 expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p< 0.02). At 8 weeks, the expression of TNFalpha and TGFbeta1 of most sites, except TGFbeta1 of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. CONCLUSION: This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of TNFalpha and TGFbeta1 at 2 weeks and TGFbeta1 at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine (TNFalpha) and fibrogenic cytokine (TGFbeta1) probably play the role of the radioprotective mechanism in Captopril.