Cardioprotective effects of zofenopril, enalapril and valsartan against ischaemia/reperfusion injury as well as doxorubicin cardiotoxicity

Abstract

Objective The aim of this study is to compare possible protective effects of zofenopril, enalapril and valsartan against both ischaemia/reperfusion injury as well as acute doxorubicin cardiotoxicity. All three agents have never been compared in this setting before.

Methods and results Sixty-four male rats were divided into eight groups by computer-generated random numbers and each group included 8 rats. Groups 1, 2, 3 and 4, respectively, received 0.5 ml distilled water, 15 mg/kg/day zofenopril, 2 mg/kg/day enalapril, and 30 mg/kg/day valsartan intragastrically for 7 days. Groups 5, 6, 7, and 8 underwent the same procedures as groups 1, 2, 3 and 4. On the 7th day, groups 1-4 and groups 5-8, respectively, were injected with serum saline or 20 mg/kg doxorubicin intraperitoneally. On the 9th day, isolated rat hearts were perfused in the Langendorff perfusion system. At the end of each Langendorff experiment, the rat hearts were kept for histological analysis. Left ventricular systolic pressures were negatively affected by doxorubicin with ischaemia (group 5 initially: 61.4 +/- 13.6 mmHg post-ischaemic (PI): 20.7 +/- 17.5 mmHg (P=0.0002), group 6 initially: 63 +/- 18.2 mmHg - PI: 24.2 +/- 24.3 mmHg (P = 0.0135), group 7: 82 +/- 26 mmHg - PI: 14.3 +/- 12.1 mmHg (P < 0.0001), group 8:73.1 +/- 27.8 mmHg - PI: 20.4 +/- 27.3 mmHg (P<0.0001). The lowest troponin 1 levels (group 2: 0.3 +/- 0.2 ng/ml, group 6: 0.2 +/- 0.1 ng/ml (P = 0.003) versus the groups' baseline value) were recorded in the groups of zofenopril in the coronary perfusate during post-ischaemic period. Light microscopic evaluation revealed marked cardiac damage with doxorubicin, since zofenopril treatment prevented a doxorubicin induced increase in the histopathological scores.

Conclusions In respect of our results zofenopril could be considered more effective than enalapril and valsartan in protecting against both ischaemia/reperfusion injury as well as doxorubicin induced-cardiotoxicity.