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).
Pavlica
Sanja
S
Institut für Biochemie, Medizinische Fakultät, Universität Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Gaunitz
Frank
F
Gebhardt
Rolf
R
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D020169:Caspases / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity; D005978:Glutathione / Q000032:analysis; D009474:Neurons / Q000187:drug effects*; D009963:Orotic Acid / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D019345:Zinc Acetate / Q000633:toxicity; D017967:Zinc Compounds / Q000633:toxicity*; D019287:Zinc Sulfate / Q000633:toxicity
D002712:Chlorides; D017967:Zinc Compounds; D009963:Orotic Acid; D019287:Zinc Sulfate; C016837:zinc chloride; D000255:Adenosine Triphosphate; D020169:Caspases; D019345:Zinc Acetate; D005978:Glutathione