Comparison of uptake and neuroprotective potential of seven zinc-salts

Zinc plays an important role as an antioxidant in different cells treated with various kinds of oxidative stressors. Although intracellular Zn(2+) is important in many cellular events, little is known about the cellular uptake of this trace metal and the intracellular status that is required for its optimal function. Since previous reports usually employed only one type of zinc-salt, in this work was compared cellular uptake and antioxidative potential of seven zinc-salts in order to discriminate whether different counterions and ligands may influence its function. Oxidative stress was induced by peroxide or iron in neuronal PC12 cells. We compared uptake of zinc-salts into the labile Zn(2+) pool of PC12 cells as well as their effects on the prevention of cell death, glutathione depletion, lipid peroxidation and ROS production. Zinc-salts provided better protection against oxidative stress-induced in PC12 cultures by peroxide than by iron. Preincubations with zinc-salts displayed better neuroprotection in all cases than coincubations. Zinc-histidine complex was shown to be the most potent compound. Our results indicated that protective effect of zinc is not related to its uptake into PC12 cells, what is indicated by the rather low salt concentrations required for the cell protection and by the observation that despite a superior antioxidant effect of zinc-histidine, the uptake of this salt by PC12 cells was remarkably lower in comparison with other zinc-salts. Although zinc-sulfate exerted weak neuroprotective potential, accumulation of Zn(2+) from this salt within cells was significantly higher compared to other salts. The differences in accumulation of zinc-salts were not specific and unique to PC12 cells, since similar results were obtained in rat primary hepatocytes and endothelial HUVEC cells.