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

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.