The Radioprotective Effect and Mechanism of Captopril on Radiation Induced-Heart Damage in Rats

Chang, Seung Hee; Lee, Kyung Ja; Koo, Heasoo

Abstract

PURPOSE: Captopril (angiotension converting enzyme inhibitor) is known to have a radioprotective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotective effect and mechanism of captopril in the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats.
MATERIALS AND METHODS
The histopathological changes and immunohistochemical stains (TNF alpha, TGFbeta1, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment.
RESULTS
In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of TNF-alpha, TGF-beta1, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial TNF-alpha and TGF-beta1 in the radiation alone group continuously increased. The expressions of TNF-alpha, TGF-beta1 and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of TNF-alpha in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009).
CONCLUSIONS
This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of TNF-alpha, TGF-beta1 and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.