| Tetrachlorobisphenol A（TCBPA）and tetrabromobisphenol S（TBBPS）have been widely used as substitutes for tetrabromobisphenol A in recent years,resulting in their high frequency detection in the environment.Some studies have shown that TCBPA and TBBPS have endocrine disrupting effects,cytotoxicity,hepatotoxicity and neurotoxicity.However,at present,there are still few studies on their toxic effects and mechanisms on fish.In this study,zebrafish was used as an aquatic model organism to study the effects of TCBPA and TBBPS on the early development of zebrafish and related neurotoxic mechanisms:Research has shown that zebrafish embryos are exposed to TCBPA at a half lethal concentration(LC50)of 0.628 mg/L for 120 hours,based on this.zebrafish embryos were exposed to TCBPA at different concentrations（0,2,20 and 200μg/L）for 120 hours post fertilization（hpf）and the developmental endpoints and locomotion behavior of larvae were measured.To explore the potential mechanisms of TCBPA,the acridine orange（OA）staining,the contents of malonic dialdehyde（MDA）,superoxide dismutase（SOD）,dopamine（DA）and express of genes related to the cell apoptosis and dopamine signaling pathway were analyses.The results showed that TCBPA significantly decreased the swimming speed at the maximum exposure concentration,accompanied by a decrease in zebrafish larvae dopamine content and significant cell apoptosis in brain.Furthermore,the expression of genes related to cell apoptosis（p53 and bax）and dopamine signaling pathway（bdnf,th,dat,drd1 and drd2）were significantly changed.Our results demonstrate TCBPA exposure can induce cell apoptosis and decrease the DA content,and subsequently affect the locomotion behavior of zebrafish larvae.Our study can provide direct scientific evidence for identifying TCBPA risk assessment.Research has shown that the half lethal concentration(LC50)of 96-hpf in zebrafish embryos exposed to TBBPS is 5.73mg/L,based on this.zebrafish embryos were exposed to TBBPS at different concentrations（0,5,50 and 500μg/L）for 120 hours post fertilization（hpf）.The effects of TBBPS on the development of zebrafish larvae were evaluated by measuring endpoint development indicators such as mortality,hatching rate,deformity rate,and body length;The effects of TCBPA on the neurodevelopment of larvae were evaluated by measuring motor behavior under light and dark cycle stimulation;The molecular mechanism of TBBPS neurotoxicity in zebrafish larvae was elucidated by detecting the content of neurotransmitters（dopamine and acetylcholine）,the expression of dopamine pathway related genes,and the activity of acetylcholinesterase;Detect the expression of genes related to the muscle system,visual system,and energy metabolism system to clarify the potential toxic mechanism of TBBPS causing low activity in young zebrafish larvae.This study suggests that changes in the content of acetylcholine may be the reason why TBBPS leads to decreased athletic activity in young zebrafish.In summary,exposure to TBBPA and TBBPS,substitutes for TBBPA,can affect the development of zebrafish larvae,and induce neurotoxicity.Relevant research results indicate that TCBPA and TBBPS need to be cautious as substitutes for TBBPA,which is of great significance for the environmental health and ecological risk assessment of TCBPA and TBBPS. |
