The possible hormetic effects of fluorene-9-bisphenol on regulating hypothalamic-pituitary-thyroid axis in zebrafish
The possible hormetic effects of fluorene-9-bisphenol on regulating hypothalamic-pituitary-thyroid axis in zebrafish
复制标题
9-芴双酚对调节斑马鱼下丘脑-垂体-甲状腺轴可能的激效作用
DOI：
10.1016/j.scitotenv.2021.145963
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发表时间：
2021
影响因子：
9.8
通讯作者：
Liu Kechun
中科院分区：
文献类型：
--
作者：
Jin Meng;Dang Jiao;Paudel Yam Nath;Wang Xixin;Wang Baokun;Wang Lizhen;Li Peihai;Sun Chen;Liu Kechun
芴-9-双酚（BHPF）是一种双酚a替代品，已被引入生产所谓的“无双酚a （BPA）”塑料。然而，据报道，BHPF可以通过使用商业塑料瓶进入生物体并造成不良影响。迄今为止，对BHPF的大多数毒理学研究都集中在调查其超过毒理学阈值的剂量。在此，我们研究了BHPF对斑马鱼发育、运动、中枢神经系统（CNS）神经元分化以及下丘脑-垂体-甲状腺（HPT）轴基因表达的影响，暴露于1/5 LD1至LD50（300、500、750、1500、3000和4500 nM）不同剂量的BHPF。结果表明，BHPF对HPT轴的调节可能具有激效作用，即低剂量BHPF对HPT轴有正向影响，而随着剂量的增加，这种调节作用被抑制。潜在机制研究表明BHPF通过影响HPT轴包括相关基因表达和TH水平破坏髓鞘形成，从而引起神经毒性特征。总的来说，这项研究提供了对BHPF的环境影响及其对生物体的毒性的充分理解，强调了大量和普遍的持续剂量-反应关系，对BHPF的使用和风险评估具有重要意义。
Fluorene-9-bisphenol (BHPF) is a bisphenol A substitute, which has been introduced for the production of so-called ‘bisphenol A (BPA)-free’ plastics. However, it has been reported that BHPF can enter living organisms through using commercial plastic bottles and cause adverse effects. To date, the majority of the toxicologic study of BHPF focused on investigating its doses above the toxicological threshold. Here, we studied the effects of BHPF on development, locomotion, neuron differentiation of the central nervous system (CNS), and the expression of genes in the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish exposed to different doses of BHPF ranging from 1/5 of LD1 to LD50 (300, 500, 750, 1500, 3000, and 4500 nM). As a result, the possible hormetic effects of BHPF on regulating the HPT axis were revealed, in which low-dose BHPF positively affected the HPT axis while this regulation was inhibited as the dose increased. Underlying mechanism investigation suggested that BHPF disrupted myelination through affecting HPT axis including related genes expression and TH levels, thus causing neurotoxic characteristics. Collectively, this study provides the full understanding of the environmental impact of BHPF and its toxicity on living organisms, highlighting a substantial and generalized ongoing dose-response relationship with great implications for the usage and risk assessment of BHPF.