Procyanidins produce significant attenuation of doxorubicin-induced cardiotoxicity via suppression of oxidative stress

Abstract

Doxorubicin is widely prescribed in the chemotherapy of haematological malignancies and solid tumours. The major side effect of doxorubicin is oxidative injury-related cardiotoxicity, which has dramatically hindered its usage. Procyanidins from grape seeds are potent free radical scavengers that have been shown to protect against anthracycline-induced cardiotoxicity. In the present study, we tested whether procyanidins would prevent the doxorubicin-induced cardiotoxicity in rats. Rats were intraperitoneally treated with doxorubicin at a cumulative dose of 15 mg/kg with and without pre-administration of procyanidins. Our data showed that doxorubicin led to cardiac function deterioration, myocardial injury and increased oxidative stress in cardiac tissues. The cardiac function deterioration by doxorubicin included increased QT-interval and ST-interval in electrocardiograph (ECG) and decreased left ventricular developed pressure. Doxorubicin-induced myocardial injury was shown by the increased creatine kinase, alanine aminotransferase and aspartate aminotransferase in serum as well as in myocardial lesions. Pretreatment with procyanidin (150 mg/kg daily) effectively hindered the adverse effects of doxorubicin, such as myocardial injury and impaired heart function. Procyanidin pretreatment attenuated cytoplasmic vacuolization, increased left ventricular developed pressure and improved the ECG. The cardioprotective effect of procyanidin corresponded to the decrease of lipid peroxidation and the increase of cardiac antioxidant potency in doxorubicin-treated rats that were also given procyanidin. An in vitro cytotoxic study showed that procyanidins did not attenuate the antineoplastic activity of doxorubicin to A549 adenocarcinoma cells. All the above lines of evidence suggest that procyanidins protect cardiomyocytes from doxorubicin-induced cardiotoxicity via suppression of oxidative stress.