Synergistic effects of lead and copper co-exposure on promoting oxidative stress and apoptosis in the neuronal cells

Exposure to lead (Pb) or copper (Cu) is common and has been associated with increased risk of neurodegenerative disease. However, combined neurotoxic effects of co-exposure to these elements remain unclear. This study aimed to determine the toxic effects of Pb and Cu co-exposure on HT22 cells. In this study, Pb and Cu co-exposure exhibited enhanced toxicity, including increased reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, Superoxide Dismutase 1 (SOD1) activity, lower cell viability and higher apoptotic rates, compared to single-element exposure. Pb and Cu co-exposure also resulted in significantly increased cellular labile Cu level by altering the protein levels of Cu transporters, including Copper Transporter-1 (CTR1), ATPase Copper Transporting-α(ATP7A) and ATPase Copper Transporting-β (ATP7B). Treating with antioxidants or Cu chelator to the co-exposed cells blocked the reduction cell viability and elevation of apoptotic rates. This study suggests that Pb and Cu co-exposure can result in a synergistic toxicity in neuronal cells by inducing oxidative stress and apoptosis. The cellular Cu accumulation may play an important role in inducing these synergistic effects, and both antioxidation and Cu chelation may be promising control measures to alleviate the neurotoxicity of Pb and Cu co-exposure.