Nickel nanoparticles exert cytotoxic effects on trophoblast HTR-8/SVneo cells possibly via Nrf2/MAPK/caspase 3 pathway

Nickel nanoparticles are widely used in the industry and may affect the reproductive system. The potential molecular mechanism of exposing the first-trimester trophoblast cell line (HTR-8/SVneo) to nickel nanoparticles remains unclear. Hence, the aim of this study was to investigate the in vitro cytotoxicity of Ni NPs on HTR-8/ SVneo cells. HTR-8/SVneo cells were subjected to various concentrations (0, 2.5, 5, 7.5, 10, and 12.5 mu g/cm2) of Ni NPs. The toxicity of the Ni NPs was evaluated in HTR-8/SVneo cells by measuring cell viability. The un-derlying mechanism of nickel nanoparticles toxicity to HTR-8/SVneo cells was determined by measuring the content of intracellular reactive oxygen species, mitochondrial membrane potential, and the rate of cell apoptosis and cell cycle, by measuring adenosine triphosphate levels, intracellular lipid peroxidation malondialdehyde, total superoxide dismutase, and CuZn/Mn-SOD activities, and by determining proteins related to Nrf2, MAPK, and Cytochrome c. Our results showed that the nickel nanoparticles treatment reduced the viability of HTR-8/ SVneo cells, while it increased their oxidative stress and lowered their mitochondrial respiratory capacity. Additionally, the nickel nanoparticles treatment induced cell S-phase arrest and apoptosis. These molecular events may be linked to the oxidative stress-Nrf2 pathway/MAPK/Caspase 3 cascade. Thus, nickel nanoparticles exert cytotoxic effects on HTR-8/SVneo cells, which could affect the function of the placenta in human.