School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Japan; Graduate School of Integrated Arts and Sciences, Tokushima University, Tokushima 770-8513, Japan.
School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Japan; Graduate School of Integrated Arts and Sciences, Tokushima University, Tokushima 770-8513, Japan.
Environ Res. 2018 Jan;160:232-238. doi: 10.1016/j.envres.2017.09.027. Epub 2017 Oct 10.
Ziram, a dithiocarbamate fungicide, protects various vegetables and fruits against infections by fungus. Recently, there have been increasing anxieties about the risks in the use of dithiocarbamate fungicides. Our previous studies showed that Zn was a determinant of Ziram cytotoxicity. In addition, Zn is linked to HO cytotoxicity. Therefore, in this study, we aimed to test the hypothesis that Ziram could augment the cytotoxicity of HO by examining the changes induced by Ziram in some cellular parameters in rat thymic lymphocytes subjected to HO-induced oxidative stress using flow-cytometric methods with fluorescent dyes. Ziram significantly attenuated HO-induced cell death at sublethal concentrations. However, in the cells under oxidative stress elicited by HO, Ziram promoted the changing over from intact cells to living cells with exposed phosphatidylserine (PS) on plasma membranes, whereas it inhibited the transition from PS-exposed living cells to dead cells. Ziram significantly augmented HO actions, including reduction of cellular glutathione levels and elevation of intracellular Zn concentrations. Conversely, it attenuated HO-induced depolarization of mitochondrial membrane potential. Ziram at sublethal concentrations seems to exhibit promotive and suppressive actions on the process of cell death caused by HO. Ziram increased the number of living cells with exposed PS, a phenomenon characteristic of early stages of apoptosis. Thus, it is concluded that Ziram exhibits pseudo-cytoprotective actions against HO-induced oxidative stress. Ziram at sublethal concentrations exerts promotive and suppressive actions on the process of cell death caused by oxidative stress.
福美锌，一种二硫代氨基甲酸盐类杀菌剂，可保护各种蔬菜和水果免受真菌感染。最近，人们对使用二硫代氨基甲酸盐类杀菌剂的风险越来越担忧。我们之前的研究表明，锌是福美锌细胞毒性的决定因素。此外，锌与 HO 的细胞毒性有关。因此，在这项研究中，我们旨在通过使用荧光染料流式细胞术方法检测福美锌在 HO 诱导的氧化应激下对大鼠胸腺淋巴细胞某些细胞参数的变化，来检验福美锌可以增强 HO 细胞毒性的假设。福美锌在亚致死浓度下显著减弱了 HO 诱导的细胞死亡。然而，在 HO 诱导的氧化应激下的细胞中，福美锌促进了从完整细胞向质膜上暴露磷脂酰丝氨酸（PS）的活细胞的转变，而抑制了从 PS 暴露的活细胞向死细胞的转变。福美锌显著增强了 HO 的作用，包括降低细胞内谷胱甘肽水平和增加细胞内锌浓度。相反，它减弱了 HO 诱导的线粒体膜电位去极化。福美锌在亚致死浓度下似乎对 HO 诱导的细胞死亡过程表现出促进和抑制作用。福美锌增加了暴露 PS 的活细胞数量，这是细胞凋亡早期的特征性现象。因此，可以得出结论，福美锌对 HO 诱导的氧化应激表现出假性细胞保护作用。福美锌在亚致死浓度下对氧化应激诱导的细胞死亡过程表现出促进和抑制作用。
