Copper is essential for several important cellular processes, but an excess of copper can also lead to
oxidative damage. In brain, astrocytes are considered to play a pivotal role in the copper homeostasis
and antioxidative defence. To investigate whether antioxidants and copper chelators can modulate the
uptake and the toxicity of copper ions in brain astrocytes, we used primary astrocytes as cell culture
model. These cells accumulated substantial amounts of copper during exposure to copper chloride. Copper
accumulation was accompanied by a time- and concentration-dependent loss in cell viability, as
demonstrated by a lowering in cellular MTT reduction capacity and by an increase in membrane permeability
for propidium iodide. During incubations in the presence of the antioxidants ascorbate, trolox or
ebselen, the specific cellular copper content and the toxicity in copper chloride-treated astrocyte cultures
were strongly increased. In contrast, the presence of the copper chelators bathocuproine disulfonate or
tetrathiomolybdate lowered the cellular copper accumulation and the copper-induced as well as the
ascorbate-accelerated copper toxicity was fully prevented. These data suggest that predominantly the
cellular content of copper determines copper-induced toxicity in brain astrocytes.