Toxicity of copper salts is dependent on solubility profile and cell type tested

Copper (Cu) is considered an essential metal for living organisms. However, disruption of Cu homeostasis is toxic and can lead to disorders such as Menkes and Wilson's diseases. The brain appears to be a vulnerable target organ. This study investigated the toxicity of Cu based on its solubility profile and cell type tested. Human A-172 (glioblastoma), SK-N-SH (neuroblastoma) and CCF-STTG1 (astrocytoma) cells were assessed after exposure to different concentrations (0.5-500μM) of copper sulfate (CuSO4) or copper (II) oxide (CuO). Since Cu is a redox active transition metal, we hypothesized that oxidative stress would be the main mechanism underlying cell toxicity. Therefore, cell viability was correlated with the extent of reactive oxygen species (ROS) formation. Cell viability decreased at the higher concentrations of the Cu salts and CuO was more toxic compared to CuSO4. The astrocytoma and glioblastoma cells were more vulnerable compared to the neuronal cells. Furthermore, it appears that oxidative stress only partially accounts for Cu-induced cell toxicity. Further studies are needed to better understand the unique susceptibility of glial cells and determine the physicochemical properties of insoluble Cu which accounts for its enhanced toxicity.