Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity
Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity
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DOI：
10.3109/0886022x.2012.656563
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发表时间：
2012-01-01
期刊：
影响因子：
3
通讯作者：
Al, Sait
中科院分区：
文献类型：
--
作者：
Ozkan, Gulsum;Ulusoy, Sukru;Al, Sait
目的：环孢素A(CsA)是一种免疫抑制药，但心脏毒性是其副作用之一。自由基损伤和细胞凋亡被认为是环孢素A所致心脏毒性的原因。葡萄籽原花青素提取物(GSPE)具有抗氧化和抗细胞凋亡活性。因此，我们旨在评价GSPE对CsA心脏毒性的影响。材料和方法：24只大鼠随机分为4组，每组6只。用25 mg/kg CsA诱导大鼠CsA肾病模型。实验于第21天结束，测定总氧化剂系统(TOS)、总抗氧化系统(TAS)、氧化应激指数(OSI)和丙二醛(MDA)，以评价心肌组织的氧化损伤。除心脏组织病理学检查外，还采用转移酶介导的脱氧尿嘧啶核苷缺口末端标记法(TUNEL)检测细胞凋亡。结果：CsA组TOS、OSI、MDA、心脏组织病理学评分和细胞凋亡指数(AI)显著升高，CsA+GSPE组OSI、MDA、心脏组织病理学评分和AI显著降低，TAS水平显著升高。结论：在这项研究中，我们首次在文献中证明了GSPE可以预防CsA的心脏毒性，并且这种作用可以通过抗细胞凋亡和抗氧化作用来实现。
Objectives: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. Materials and methods: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. Conclusion: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities