4.7 Article

Ziram, a dithiocarbamate fungicide, exhibits pseudo-cytoprotective actions against oxidative stress in rat thymocytes: Possible environmental risks

期刊

ENVIRONMENTAL RESEARCH
卷 160, 期 -, 页码 232-238

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.envres.2017.09.027

关键词

Ziram; Lymphocytes; Cytoprotective action; Oxidative stress; Flow cytometer

资金

  1. Japan Society for the Promotion of Science [C26340039]
  2. Grants-in-Aid for Scientific Research [16K13050, 26340039] Funding Source: KAKEN

向作者/读者索取更多资源

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 Zn2+ was a determinant of Ziram cytotoxicity. In addition, Zn2+ is linked to H2O2 cytotoxicity. Therefore, in this study, we aimed to test the hypothesis that Ziram could augment the cytotoxicity of H2O2 by examining the changes induced by Ziram in some cellular parameters in rat thymic lymphocytes subjected to H2O2-induced oxidative stress using flow-cytometric methods with fluorescent dyes. Ziram significantly attenuated H2O2-induced cell death at sublethal concentrations. However, in the cells under oxidative stress elicited by H2O2, 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 H2O2 actions, including reduction of cellular glutathione levels and elevation of intracellular Zn2+ concentrations. Conversely, it attenuated H2O2-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 H2O2. 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 pseudocytoprotective actions against H2O2-induced oxidative stress. Ziram at sublethal concentrations exerts promotive and suppressive actions on the process of cell death caused by oxidative stress.

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