Neurotoxicity of BPA, BPS, and BPB for the hippocampal cell line (HT-22): An implication for the replacement of BPA in plastics

Abstract

Bisphenol A (BPA), a plastic additive, is ubiquitous in the environment and has endocrine disrupting effects. As many countries have prohibited the manufacture and sale of plastic products with BPA, BPA analogs have been used to replace BPA during production, including bisphenol S (BPS) and bisphenol B (BPB). To investigate the toxicities of BPA and its analogs on neurons, reactive oxygen species (ROS) assay, Annexin V-FITC (fluorescein) apoptosis detection assay, lactate dehydrogenase (LDH) cytotoxicity assay, and Cell Counting Kit-8 assay were conducted to comprehensively assess the influence of different concentrations of BPA, BPB, and BPS on ROS, apoptosis, damage, and proliferation for hippocampal HT-22 cells, respectively. Results showed that 6 h of exposure to bisphenols (BPs) could increase the ROS levels, 24 h and 48 h of exposure could induce higher apoptosis and LDH leakage rates for HT-22 cells, and 7 d of exposure could inhibit the cell proliferations. In addition, non-monotonic dose-response relationships were observed between the concentrations of bisphenols and the toxic effects mentioned above. The neurotoxic effects of BPA, BPB and BPS on HT-22 cells were in the increasing order of BPS, BPA, and BPB. In conclusion, these results showed that exposure to BPA and its analogs may result in adverse effects on hippocampal neuronal cell lines. BPS is a surrogate with lower neurotoxicity to replace BPA in production of plastic utensils.