Oxidative Stress and Apoptosis in Bisphenol AF–Induced Neurotoxicity in Zebrafish Embryos
Eric Gyimah, Xian Zhu, Ziqi Zhang, Mengyuan Guo, Hai Xu, John Kenneth Mensah, Xing Dong, Zhen Zhang, Godfred Nana Wireko Gyimah
Abstract
Bisphenol AF (BPAF) is a structural counterpart of bisphenol A that is utilized in the food and beverage industry. The present study investigated the potential mechanisms in BPAF-induced neurotoxicity in zebrafish embryos. The BPAF concentrations (0.03, 0.1, 0.3, and 1.0 µM) had no obvious effect on hatching, mortality, and body length of zebrafish larvae, while curved tail and pericardial edema were observed in the 1.0 μM group at 72 and 96 h postfertilization (hpf). Locomotor activity of the larvae (at 120 hpf) significantly decreased from dark to light but increased from light to dark transitions in BPAF groups (0.1, 0.3, and 1.0 μM). Acridine orange showed that BPAF significantly increased green fluorescence protein intensity (22.6%) in the 1.0 μM group. Consistently, the induced apoptosis significantly up-regulated caspase 3 at 0.3 μM (1.95-fold) and 1.0 μM (2.26-fold) and bax at 0.3 μM (1.60-fold) and 1.0 μM (1.78-fold), whereas bcl-2 expression was significantly decreased at 0.3 μM (0.72-fold) and 1.0 μM (0.53-fold). In addition, increased reactive oxygen species concentrations at 0.3 μM (27%) and 1.0 μM (61.4%) resulted in suppressed superoxide dismutase and catalase activities. Moreover, quantitative polymerase chain reaction results showed that BPAF (0.3 and 1.0 μM) significantly altered normal dopaminergic signaling where dat was up-regulated, while drd2a and th1 were down-regulated, in a concentration-dependent manner. Aberrations in dopamine-related genes were congruous with the dysregulations in neurodevelopment genes (sox11b, pax6a, syn2a, and rob2). Our findings suggest that BPAF-evoked oxidative stress and apoptosis could translate into phenotypical behavioral and neurodevelopmental abnormalities. These highlights could provide theoretical reference for risk assessment and act as an early indicator to BPAF exposure. Environ Toxicol Chem 2022;41:2273-2284. © 2022 SETAC.