Grape Seed and Skin Extract Protects Against Acute Chemotherapy Toxicity induced by Doxorubicin in Rat Heart
Grape Seed and Skin Extract Protects Against Acute Chemotherapy Toxicity induced by Doxorubicin in Rat Heart
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DOI:
10.1007/s12012-012-9155-1
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发表时间:
2012-06-01
影响因子:
3.2
通讯作者:
Aouani, Ezzedine
中科院分区:
文献类型:
--
作者:
Mokni, Meherzia;Hamlaoui-Guesmi, Sonia;Aouani, Ezzedine
Doxorubicin (Dox), an antitumor anthracycline antibiotic, plays a key role in the treatment of many neoplastic diseases. However, its chronic administration induces cardiomyopathy. Increased oxidative stress is a major factor implicated in Dox-induced cardiotoxicity. We hypothesized that a pre-treatment with grape seed and skin extract (GSE), commonly used as an antioxidant agent, may alleviate this cardiotoxicity. Rats were treated with GSE (500 mg/kg ) by intraperitoneal injection during 8 days. On the 4th day, rats were administered a single dose of Dox (20 mg/kg). At the end of the treatment, their hearts were Langendorff-perfused, subjected to ischemia/reperfusion (I/R) injury, and left ventricular functions as heart rate and developed pressure measured. Hearts were also used to determine free iron, H2O2, Ca2+, lipoperoxidation, carbonylation and antioxidant enzymes such as superoxide dismutase (SOD), catalase and peroxidase. Doxorubicin drastically affected heart activity as evidenced after I/R experiments. This effect was associated with an increase in heart free iron and a decrease in Ca2+ concentrations. This effect may have contributed to oxidative stress as assessed by high lipoperoxidation and carbonylation level. GSE counteracted Dox-induced disturbances of hemodynamic parameters, alleviated oxidative stress as assessed by normalized iron and Ca2+ levels and increased SOD activity especially the Mn isoform.