Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
Food Chem Toxicol. 2011 Oct;49(10):2564-74. doi: 10.1016/j.fct.2011.06.072. Epub 2011 Jul 1.
Tellurium tetrachloride (TeCl(4)) and diphenyl ditelluride (DPDT) cytotoxicity, was investigated in rat astrocytes. Concentrations of 0.24-250μM (24h) were tested for viability using MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and trypan blue exclusion. MTT showed significant decreases at all concentrations tested for both compounds. Significant decreases in viability were seen in 1.95-250μM of DPDT and 0.97-250μM of TeCl(4) with trypan blue exclusion. The LC(50) for both compounds was 62.5μM. Light and scanning microscopy confirm toxicity observed at higher concentrations. Thiobarbituric acid reactive substances (TBARs) assay, TUNEL, cytochrome c and caspase release were carried out. No significant increase in TBARS with either agent was observed (15.625-62.5μM). TUNEL and cytochrome c assays demonstrated apoptosis in TeCl(4) treated cells (31.25-125μM). Non-apoptotic cells were observed in DPDT treated cells. Studies of caspase 3/7 and caspase 9 indicated increased activity in TeCl(4) but not in DPDT treated cells. Optical Emission Spectroscopy of DPDT and TeCl(4) treated cells demonstrated significant accumulation of elemental tellurium in all treatment groups (31.25-125μM). We conclude that DPDT and TeCl(4) are cytotoxic to astrocytes. TeCl(4) treated cells die via the intrinsic apoptotic pathway. Accumulation of tellurium occurs with both compounds, but results in different mechanisms of cell death.
四氯化碲(TeCl(4))和二苯二碲(DPDT)对大鼠星形胶质细胞的细胞毒性进行了研究。使用 MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐)和台盼蓝排除法检测了 0.24-250μM(24 小时)的浓度对活力的影响。MTT 显示两种化合物在所有测试浓度下均显著降低。用台盼蓝排除法观察到 1.95-250μM 的 DPDT 和 0.97-250μM 的 TeCl(4) 可显著降低细胞活力。两种化合物的 LC(50)均为 62.5μM。光镜和扫描电镜证实了在较高浓度下观察到的毒性。进行了硫代巴比妥酸反应性物质(TBARs)测定、TUNEL、细胞色素 c 和半胱天冬酶释放。两种试剂均未观察到 TBARs 显著增加(15.625-62.5μM)。TUNEL 和细胞色素 c 测定表明 TeCl(4)处理的细胞发生了细胞凋亡(31.25-125μM)。DPDT 处理的细胞中观察到非凋亡细胞。半胱天冬酶 3/7 和半胱天冬酶 9 的研究表明,TeCl(4)处理的细胞中活性增加,但 DPDT 处理的细胞中没有。DPDT 和 TeCl(4)处理细胞的光学发射光谱显示,所有处理组(31.25-125μM)均有大量碲元素积累。我们得出结论,DPDT 和 TeCl(4)对星形胶质细胞均具有细胞毒性。TeCl(4)处理的细胞通过内在凋亡途径死亡。两种化合物均会发生碲的积累,但导致不同的细胞死亡机制。