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Neurodevelopmental toxicity of organophosphate flame retardant triphenyl phosphate (TPhP) on zebrafish (Danio rerio) at different life stages

斑马鱼 磷酸三苯酯 有机磷 达尼奥 发育毒性 生物 多溴联苯醚 毒性 内科学 细胞生物学 内分泌学 化学 阻燃剂 生物化学 遗传学 医学 基因 生态学 杀虫剂 有机化学 污染物 怀孕 妊娠期
作者
Qiong Zhang,Shukai Zheng,Xiaoling Shi,Congying Luo,Wenlong Huang,Henghui Lin,Jiajun Peng,Wei Tan,Kusheng Wu
出处
期刊:Environment International [Elsevier BV]
卷期号:172: 107745-107745 被引量:54
标识
DOI:10.1016/j.envint.2023.107745
摘要

As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms. TPhP concentration gradient exposure reduced the survival rate, hatchability, heart rate, body length and eye distance of zebrafish embryos/larvae, and caused malformations of zebrafish larvae. TPhP also leads to abnormal locomotor behaviors, such as reduced swimming distance and swimming speed, and impaired panic avoidance reflex to high light stimulation. TPhP caused ROS accumulation in 96 hpf larvae and induced Nrf2-antioxidant response in zebrafish. In addition, TPhP further activated mitochondrial signaling pathways, which affected apoptosis in the zebrafish eye region, resulting in visual impairment. Neurodevelopmental (mbpa, syn2a, foxo3a and pax6a), Retinoid acid metabolism (cyp26a1, raraa, rbp5, rdh1, crabp1a and rbp2a) and apoptosis-related genes (bcl2a, baxa and casp9) revealed the molecular mechanism of abnormal behavior and phenotypic symptoms, and also indicated that 96 hpf larvae are more sensitive than 7 dpf larvae. Thus, in the present study, we revealed the neurotoxic effects of TPhP at different early life stages in zebrafish, and zebrafish locomotor behavior impairments induced by TPhP exposure are attributed to co-regulation of visuomotor dysfunction and neuro-related genes. These results suggest that the safety of TPhP in organisms and even in humans needs to be further studied.
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