4.7 Article

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

Journal

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 207, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2020.111299

Keywords

Bisphenol A; Oxidative stress; Apoptosis; Mitochondria; Neurotoxicity

Funding

  1. National Natural Science Foundation of China [21777048, 41731279, 21477041]

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The analogues of BPA, BPS and BPB, may induce oxidative stress and apoptosis in neuroblastoma cells, with males being more susceptible to BPs. Interestingly, BPS shows lower neurotoxic effects compared to BPA and BPB with BPA having a significantly higher impact on IMR-32 cells than on SK-N-SH cells.
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 mu M, 10 mu M, and 100 mu M for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 mu M and 8 mu M 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 alle-viated 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.

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