Abstract
Purpose: The aim of the present study was to determine the ability of grape seed extract (GSE) as a powerful antioxidant in preventing adverse effect of doxorubicin (DOX) on heart function. Methods: Male rats were divided into three groups: control, DOX (2 mg/kg/48h, for 12 days) and GSE (100 mg/kg/24h, for 16 days) plus DOX. Left ventricular (LV) function and hemodynamic parameters were assessed using echocardiography, electrocardiography and a Millar pressure catheter. Histopathological analysis and in vitro antitumor activity were also evaluated. Results: DOX induced heart damage in rats through decreasing the left ventricular systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening and contractility index as demonstrated by echocardiography, electrocardiography and hemodynamic parameters relative to control group. Our data demonstrated that GSE treatment markedly attenuated DOX-induced toxicity, structural changes in myocardium and improved ventricular function. Additionally, GSE did not intervene with the antitumor effect of DOX. Conclusion: Collectively, the results suggest that GSE is potentially protective against DOX-induced toxicity in rat heart and maybe increase therapeutic index of DOX in human cancer treatment.
Highlights
Doxorubicin (DOX), an anthracycline antibiotic, is wellknown as one of the most widely-used chemotherapeutic drugs which has been shown to be highly effective in the treatment of a broad spectrum of human cancers.[1]
Grape seeds (Vitis vinifera) were washed with water and crushed, the crude extract was partitioned between H2O and n-hexane for separating lipoid compounds, grape seed extract (GSE) was prepared by using ethanol 95% and water as solvents with mechanical agitation for 2 to 3 h, this process was repeated twice
Echocardiographic analysis To evaluate the influence of the GSE and DOX on Left ventricular (LV) remodeling and function, a series of echocardiography studies were conducted
Summary
Doxorubicin (DOX), an anthracycline antibiotic, is wellknown as one of the most widely-used chemotherapeutic drugs which has been shown to be highly effective in the treatment of a broad spectrum of human cancers.[1]. One of the phytochemicals extensively investigated in recent years is grape seed extract (GSE). This extract, an excellent source of natural antioxidants, is used in the pharmaceutical, cosmetic and food industries.[5,6] Effects of GSE on improvement of liver function,[7] reducing infarct size and cardiac arrhythmias,[8] lipid profile[9] and lipid peroxidation[10] in patients with type II diabetes have been reported previously. Some studies have unequivocally demonstrated that GSE has substantial potential for scavenging free radicals in both in vitro and in vivo experimental models.[5,6,11] An excellent example comes from recent investigations where grape seed proanthocyanidins extract has been shown to be a superior scavenger against superoxide anion and hydroxyl radicals in comparison with vitamins C, E and β-carotene.[12]
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