Department of Neurology, The Ninth People's Hospital of Chongqing , Chongqing , China .
Toxicol Mech Methods. 2013 Nov;23(9):665-71. doi: 10.3109/15376516.2013.837130. Epub 2013 Sep 19.
Vinorebine (VNR), a second-generation vinca alkaloid antitumor drug, caused serious local venous toxicities, such as venous irritation, phlebitis and necrotizing vasculitis. This study investigated whether resveratrol (RES), a naturally occurring polyphenol compound, could reduce the vascular injury induced by VNR. Human vascular endothelial cell line ECV-304 cells were exposed to VNR for 10 min and then cells were cultured with serum-free medium with or without RES for 24 h. MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphe-nyl-2-tetrazolium bromide) assay was used to detect the cell viability. Reactive oxygen species (ROS) was measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The activity of superoxide dismutase (SOD) was assessed by SOD detection kit. VNR decreased the viability of ECV-304 cells in a dose-dependent manner. Moreover, VNR caused cell apoptosis, the generation of intracellular ROS and the reduction of intracellular SOD. Interestingly, pretreatment with RES for 2 h increased the cell viability in a dose-dependent manner. Cell apoptosis, the intracellular ROS generation and the reduction of intracellular SOD induced by VNR were also attenuated when cells were pretreated with RES for 2 h. These results demonstrated that RES would protect against vascular endothelial cell injury induced by VNR. So the use of RES together with VNR may be a possible therapeutic approach to avoid the vascular injury induced by VNR.
长春碱（VNR）是第二代长春花生物碱抗肿瘤药物，会引起严重的局部静脉毒性，如静脉刺激、静脉炎和坏死性血管炎。本研究探讨了白藜芦醇（RES），一种天然存在的多酚化合物，是否可以减轻 VNR 引起的血管损伤。将人血管内皮细胞系 ECV-304 细胞暴露于 VNR 10 分钟，然后用无血清培养基培养细胞，同时加入或不加入 RES 24 小时。用 MTT（3-[4,5-二甲基-2-噻唑基]-2,5-二苯基-2-四唑溴盐）测定法检测细胞活力。用 2',7'-二氯荧光素二乙酸酯（DCFH-DA）测定活性氧（ROS）。用 SOD 检测试剂盒评估超氧化物歧化酶（SOD）的活性。VNR 以剂量依赖性方式降低 ECV-304 细胞的活力。此外，VNR 引起细胞凋亡、细胞内 ROS 的产生和细胞内 SOD 的减少。有趣的是，用 RES 预处理 2 小时以剂量依赖性方式增加细胞活力。当细胞用 RES 预处理 2 小时时，VNR 诱导的细胞凋亡、细胞内 ROS 的产生和细胞内 SOD 的减少也得到了减弱。这些结果表明，RES 可防止 VNR 引起的血管内皮细胞损伤。因此，将 RES 与 VNR 一起使用可能是避免 VNR 引起的血管损伤的一种可行的治疗方法。
