Bisphenol A(BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines.

ABSTRACT

The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 µM, 10 µM, and 100 µM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 µM and 8 µM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.