Sex-specific oxidative damage effects induced by BPA and its analogs on primary hippocampal neurons attenuated by EGCG

Abstract

BPA analogs, including bisphenol S (BPS) and bisphenol B (BPB), have been used to replace BPA since it was banned to be added. To investigate whether BPA and its analogs cause oxidative damage effects on primary hippocampal neurons of rats, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), mitochondrial membrane potential (MMP), apoptosis and cell viability assays were conducted after hippocampal neurons exposure to different concentrations of BPA, BPS, and BPB (1, 10, 100 nM and 1, 10, 100 μM). Moreover, the effects of EGCG (5 and 6 μM for male and female, respectively) added on neurons exposed to BPA were assessed. Results showed that 24 h exposure to these bisphenols (BPs) could increase the levels of ROS and contents of MDA, but reduce the activity of SOD significantly. A decline of cell viabilities accompanied with the increasing of apoptosis rates was observed after 7 d exposure to BPs and the reduction of MMP was also observed after 7 d exposure to BPA. Interestingly, BPS has the lower toxicity to hippocampal neurons compared with BPA and BPB. Non-monotonic dose-effect relationships between the concentrations of BPs and the cytotoxic effects were observed, and the effects of BPs on male hippocampal neurons are greater than those of female ones in general. While EGCG can protect neurons free of oxidative damages. In conclusion, the results suggest that BPs may induce sex-specific neurotoxic effects involving oxidative stress, which can be attenuated by EGCG, and males are more sensitive to BPs than females.