Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells
Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells
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DOI：
10.2131/jts.36.155
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发表时间：
2011-04-01
影响因子：
2
通讯作者：
Satoh, Masahiko
中科院分区：
文献类型：
--
作者：
Fujiwara, Yasuyuki;Banno, Hiroki;Satoh, Masahiko
西洛他唑是一种抗血小板药物，具有抗动脉粥样硬化作用。本研究的目的是确定西洛他唑对培养的血管内皮细胞中镉（Cd）和亚砷酸盐（iAs(III)）的细胞毒性的影响，镉（Cd）和亚砷酸盐（iAs(III)）参与动脉粥样硬化等血管疾病的发病机制。通过乳酸脱氢酶渗漏试验和形态学观察评价细胞毒性。西洛他唑（30和100 μ M）预处理和西洛他唑（100 μ M）同时处理可预防Cd （10 μ M）诱导的细胞毒性。另一方面，用西洛他唑（30 μ M和100 μ M）预处理可以阻断iAs（III）诱导的细胞毒性，但不能同时使用西洛他唑。西洛他唑显著提高了细胞中金属硫蛋白（MT） mRNA和蛋白水平。因此，这些结果表明，西洛他唑预处理可以有效地阻止培养血管内皮细胞中Cd和iAs（III）的细胞毒性，至少部分是通过诱导MT合成来实现的。
Cilostazol, an antiplatelet drug, exhibits antiatherogenic effects. The purpose of the present study was to determine the effect of cilostazol on the cytotoxicity of cadmium (Cd) and arsenite (iAs(III)), which involved in the pathogenesis of vascular disorders such as atherosclerosis, in cultured vascular endothelial cells. Cytotoxicity was evaluated by the lactate dehydrogenase leakage assay and morphological observation. Cd (10 mu M) -induced cytotoxicity was prevented by pretreatment with cilostazol (30 and 100 mu M) and simultaneous treatment with cilostazol (100 mu M). On the other hand, iAs(III)-induced cytotoxicity was blocked by pretreatment with cilostazol (30 and 100 mu M) but not simultaneous treatment with cilostazol. The mRNA level and the protein level of metallothionein (MT) were significantly increased by cilostazol in the cells. These results suggested, therefore, that pretreatment with cilostazol effectively prevents the cytotoxicity of Cd and iAs(III) in cultured vascular endothelial cells, at least in part through the induction of MT synthesis.