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• W2082726660 endingPage "1220" @default.
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• W2082726660 abstract "Clioquinol is emerging as a potential therapy for some diseases, such as Alzheimer disease and cancer. This agent is a lipophilic chelator of Zn2 +. In this study, the effect of clioquinol on the intracellular Zn2 + level was examined in order to gain insights into the toxicological profile of clioquinol. The effect of clioquinol was estimated using a flow cytometer and FluoZin-3, a fluorescent indicator for Zn2 +, in rat thymocytes. Clioquinol, at concentrations ranging from 10 to 300 nM, augmented FluoZin-3 fluorescence in a concentration-dependent manner. However, the effect induced by 1 μM clioquinol was less than that by 300 nM clioquinol. Removal of extracellular Zn2 +, using the membrane impermeable Zn2 +-chelator diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (DTPA), abolished the clioquinol-induced augmentation of FluoZin-3 fluorescence. Clioquinol did not augment Fluo-3 fluorescence, an indicator of intracellular Ca2 +, in the presence of DTPA. The results suggested that clioquinol caused an extracellular Zn2 +-dependent increase in the intracellular Zn2 + concentration. However, in the presence of DTPA, clioquinol at micromolar concentrations (1–10 μM) attenuated FluoZin-3 fluorescence in a concentration-dependent manner. Clioquinol even at 10 μM did not affect FluoZin-3 fluorescence under cell-free condition. The concentration–response relationship for the clioquinol induced change in Zn2 + level appeared to be bell-shaped. These results indicate that micromolar concentrations of clioquinol, without chelated Zn2 +, decrease intracellular Zn2 + concentration. The effect of clioquinol on the intracellular Zn2 + level varies, depending on the extracellular Zn2 + concentration and the clioquinol concentration. Clioquinol may therefore exert various types of Zn2 +-dependent cytotoxicity." @default.
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• W2082726660 date "2012-12-01" @default.
• W2082726660 modified "2023-09-25" @default.
• W2082726660 title "Clioquinol-induced increase and decrease in the intracellular Zn2+ level in rat thymocytes" @default.
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• W2082726660 doi "https://doi.org/10.1016/j.lfs.2012.09.014" @default.
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