Comparative in vitro toxicity of seven zinc-salts towards neuronal PC12 cells

Currently much attention has been given to the neurotoxicity of zinc, yet little is known about the influence of the counterions present. Therefore, we investigated the influence of different Zn(2+)-salts (concentrations range 0.05-0.3 mM) on cell viability, ATP and glutathione concentration and caspase activation in differentiated PC12 cells as a model for neuronal cells. Generally, at concentrations of 0.05 mM most Zn(2+)-salts were not cytotoxic except for zinc-citrate. At concentrations between 0.1 and 0.3 mM Zn(2+) a significant decrease in GSH and ATP levels preceded cell death induced by all salts, except of zinc-histidinate. Zinc-citrate and zinc-sulphate turned out to be the most toxic salts particularly at low concentrations. Analyses of caspase 3/7 activity showed that dependent on the concentration and the type of the salt used cell death may show more or less signs of both, necrosis and apoptosis. Interestingly, the uptake of Zn(2+) from zinc-sulphate and zinc-citrate was significantly higher than that of other salts, implicating a correlation between uptake and toxicity. In conclusion, Zn(2+)-salts could be divided into three categories with high (zinc-citrate, zinc-sulphate), moderate (zinc-orotate, zinc-acetate, zinc-chloride(,) zinc-gluconate) and low cytotoxicity (zinc-histidinate).