Clioquinol, a lipophilic Zn2+ chelator, augments and attenuates the cytotoxicity of H2O2: A bell-shaped response curve of the effects of the drug,
Clioquinol, a lipophilic Zn2+ chelator, augments and attenuates the cytotoxicity of H2O2: A bell-shaped response curve of the effects of the drug,
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Clioquinol 是一种亲脂性 Zn2 螯合剂，可增强和减弱 H2O2 的细胞毒性：药物作用的钟形响应曲线，
DOI：
10.1039/c3tx50097g
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发表时间：
2014
影响因子：
2.1
通讯作者：
Hitoshi Ishibashi and Yasuo Oyama
中科院分区：
文献类型：
--
作者：
Tomohiro Oyama;Keisuke Oyama;Eri Fukunaga;Hitoshi Ishibashi and Yasuo Oyama
氯碘羟喹是一种亲脂性锌离子螯合剂，已成为一种潜在的新型治疗药物，用于治疗癌症和阿尔茨海默病等多种疾病。氯碘羟喹对大鼠胸腺细胞内Zn ~（2+）浓度的影响因其浓度和细胞外Zn ~（2+）水平而异。在这项研究中，我们研究了氯碘羟喹对过氧化氢（H2 O2）诱导的氧化应激下的细胞的影响，通过使用传统的流式细胞术技术与适当的荧光探针。我们观察到氯碘喹浓度和H2 O2细胞毒性变化之间呈钟形关系;氯碘喹浓度为100 nM时，H2 O2诱导的细胞毒性最高。Zn 2+螯合剂显著降低了氯喹诺酮诱导的H2 O2细胞毒性增加。钟形曲线之间观察到的氯碘羟喹和细胞内的Zn 2+浓度的H2 O2诱导的细胞毒性的增加，虽然在Zn 2+水平的最大增加是由300 nM氯碘羟喹诱导。此外，浓度≥100 nM的氯碘羟喹通过降低细胞氧化剂水平发挥抗氧化活性。因此，氯碘羟喹可以发挥促氧化剂或抗氧化剂作用，这取决于其浓度和胞外Zn 2+浓度。由于氯碘羟喹独特的锌离子依赖性效应和毒理学特征，应考虑将氯碘羟喹用于临床。
Clioquinol, a lipophilic Zn2+chelator, has emerged as a potential novel therapeutic agent for several diseases such as cancer and Alzheimer's disease. Clioquinol has different effects on the intracellular Zn2+concentrations in rat thymocytes, depending on its concentration and extracellular Zn2+levels. In this study, we examined the effect of clioquinol on cells under oxidative stress induced by hydrogen peroxide (H2O2) by using a conventional flow cytometric technique with appropriate fluorescent probes. We observed a bell-shaped relationship between the clioquinol concentration and changes in H2O2cytotoxicity; H2O2-induced cytotoxicity was the highest at a clioquinol concentration of 100 nM. Zn2+chelators significantly decreased the clioquinol-induced increase in H2O2cytotoxicity. A bell-shaped curve was observed between the increase in H2O2-induced cytotoxicity by clioquinol and the intracellular Zn2+concentrations, although the maximal increases in Zn2+levels were induced by 300 nM clioquinol. In addition, clioquinol at concentrations ≥100 nM exerted antioxidant activity by decreasing the cellular oxidant levels. Thus, clioquinol can exert pro-oxidant or antioxidant effects, depending on its concentration and the extracellular concentration of Zn2+. Because of the unique Zn2+-dependent effects and toxicological profile of clioquinol, clioquinol should be considered for clinical use.