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.

双酚A（BPA）的类似物，包括双酚S（BPS）和双酚B（BPB），通常用于代替BPA在日常生活的容器和包装纸中的应用。但是，由于它们的化学结构和BPA相似，因此它们的安全性受到质疑。为了研究BPA，BPS和BPB的神经毒性及其潜在机制，将雄性的IMR-32细胞系和雌性的SK-N-SH细胞系分别暴露于浓度为1 nM的BPA，BPS和BPB ，10 nM，100 nM，1μM，10μM和100μM持续24小时。此外，进行了24小时的结合表没食子儿茶素没食子酸酯（EGCG）的BPA暴露（对于IMR-32和SK-N-SH分别为4μM和8μM）。结果表明，BPs暴露可以促进活性氧的产生，并提高丙二醛（MDA）的水平，同时降低超氧化物歧化酶（SOD）的水平。深入研究表明，暴露于BPA的线粒体膜电位（MMP）后下降，Bak-1，Bax，细胞色素c和Caspase-3的蛋白表达水平上调，而Bcl-2的表达明显下调。此外，在神经母细胞瘤细胞中，凋亡率增加并且细胞活性显着下降。通过添加EGCG可以减轻BPA诱导的所有作用，在BPS和BPB诱导的IMR-32和SK-N-SH细胞中也可以推断出类似的缓解作用。此外，与BPA和BPB相比，BPS表现出较低的神经毒性作用。有趣的是 BPA对IMR-32细胞的神经毒性明显高于对SK-N-SH细胞的神经毒性。总之，结果表明，BPA，BPS和BPB可以通过线粒体途径诱导神经母细胞瘤细胞中的氧化应激和凋亡，男性比女性更易受BP的影响。