Abstract
Doxorubicin is a chemotherapeutic agent known to cause cardiotoxicity that is thought to be associated with oxidative stress. The aim of the current study is to investigate the role of grape polyphenols’ antioxidant property as cardioprotective against doxorubicin-induced cardiotoxicity. Adult Wistar rats weighing 200 ± 20 g were divided into 3 different groups: a doxorubicin group that received a single intraperitoneal administration of doxorubicin (8.0 mg/kg body weight), an experimental group that received doxorubicin and grape polyphenol concentrate (25 mg/kg) via intragastric route, and the third group was a negative control group that received water only. On day 8, blood samples and tissues were harvested for analyses. The results indicated that grape polyphenol concentrate was able to reduce the signs of cardiotoxicity of doxorubicin through the reduction of aspartate aminotransferase activation, increasing the plasma antioxidant levels and decreasing the level of free radicals. The results also showed that grape polyphenol concentrate was able to reverse doxorubicin-induced microscopic myocardial damage. The myocardial protective effect of grape polyphenol might likely be due to the increase in the level and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. In conclusion, grape polyphenol concentrate displayed cardioprotective effect and was able to reverse doxorubicin-induced-cardiomyopathy in experimental rats.
Highlights
Doxorubicin is a chemotherapeutic agent known to cause cardiotoxicity that is thought to be associated with oxidative stress
Rats treated with doxorubicin showed an increased level of free radicals and significantly reduced antioxidant capacity of blood plasma, which were reversed in rats treated with grape polyphenol concentrate (Table 1)
It is well known that doxorubicin induced reactive oxygen species (ROS) lead to mitochondria damage, cell necrosis, breakdown of mitochondria, and the release of AST into the blood, which are commonly used as indication of cell cytolysis[11]
Summary
Doxorubicin is a chemotherapeutic agent known to cause cardiotoxicity that is thought to be associated with oxidative stress. The aim of the current study is to investigate the role of grape polyphenols’ antioxidant property as cardioprotective against doxorubicin-induced cardiotoxicity. The results indicated that grape polyphenol concentrate was able to reduce the signs of cardiotoxicity of doxorubicin through the reduction of aspartate aminotransferase activation, increasing the plasma antioxidant levels and decreasing the level of free radicals. The results showed that grape polyphenol concentrate was able to reverse doxorubicin-induced microscopic myocardial damage. Grape polyphenol concentrate displayed cardioprotective effect and was able to reverse doxorubicin-inducedcardiomyopathy in experimental rats. An increase of free radicals and a decrease in the activity of endogenous antioxidants in the myocardium play important roles in the pathogenesis of doxorubicin-induced heart failure. We hypothesized that the antioxidant activity of polyphenolic concentrate may play a role in the prevention or reduction of doxorubicin-induced cardiotoxicity
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