Exposure of rat hippocampal astrocytes to zinc dimethyldithiocarbamate increases oxidative stress

Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used on a variety of plant diseases. Dithiocarbamates are a family of highly reactive compounds due to their metal combining capacity and their ability to interact with sulfhydryl-containing compounds. This investigation studied the effects of Ziram on rat hippocampal astrocytes. Astrocytes were exposed to 1.0μM of Ziram for one hour at 37° C and then re-fed with complete media for 24 hours. The TBARS assay showed a significant increase, p < 0.05, in malondialdehyde, a product of lipid peroxidation, in the Ziram treated cells when compared to controls. Biochemical analysis revealed a significant increase in the induction of Hsp70, p < 0.05, and HO-1, p < 0.05, in the treated cells as compared with control cells. Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) demonstrated, in all cases of treatment with Ziram, significant increases of the copper levels as compared with controls. However, the zinc levels in the Ziram treated astrocytes and the control astrocytes were not statistically different. Morphological observations, by phase contrast and scanning electron microscopy, in treated astrocytes showed blebbing, increased numbers of retraction fibers and distortion of cellular processes. Transmission electron microscopy of Ziram treated cells showed the presence of lipid droplets, disarrayed cristae of the mitochondria and electron deposits in organelles. These data suggest that the cytotoxic effects observed in the Ziram treatments may be related to an increase in oxidative stress.