Chang Jing, Zhang Leisen, Zhao Juan, Zhang Zhaoguang, Wang Zijian, Wang Huili, Wan Bin
Laboratory for Chemical Environmental Risk Assessment, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing RD 18, Beijing 100085, China.
University of Chinese Academy of Sciences, Yuquan RD 19 a, Beijing 100049, China.
Environ Sci Technol. 2024 Dec 17;58(50):22076-22088. doi: 10.1021/acs.est.4c11264. Epub 2024 Dec 4.
N-(1,3-Dimethylbutyl)-'-phenyl-1,4-phenylenediamine (6PPD) and its oxidation product 6PPD-quinone (6PPDQ) showed different acute toxicities and bioaccumulation potencies in fish. In this study, we compared the thyroid disrupting effects of 6PPD and 6PPDQ through , , and assays. Interestingly, although 6PPD and 6PPDQ showed similar docking affinities with thyroid hormone receptor (TR) isoforms and GH3 cell inhibition effects, the thyroid signaling pathway, eye development, phototactic behaviors, and cell density in the retinal layer in the larval zebrafish were significantly affected only following 6PPD exposure. Further investigation demonstrates that 6PPD can act as a TR antagonist to reduce the opsin protein abundance and inhibit the cone photoreceptor cell proliferation, which finally alters the retinal layer structure and causes microphthalmus in zebrafish. Especially, under environmental relevant concentration exposure, 6PPD induced alterations of , , , , gene expressions although no significant eye histopathological change was observed. This study illustrates for the first time the more serious visual system impairment of 6PPD compared to 6PPDQ, with thyroid signaling disruption being a contributing factor, while other important toxic targets still require further research.
N-(1,3-二甲基丁基)-对苯基-1,4-苯二胺（6PPD）及其氧化产物6PPD-醌（6PPDQ）在鱼类中表现出不同的急性毒性和生物累积潜力。在本研究中，我们通过[此处原文缺失具体实验名称]、[此处原文缺失具体实验名称]和[此处原文缺失具体实验名称]实验比较了6PPD和6PPDQ对甲状腺的干扰作用。有趣的是，尽管6PPD和6PPDQ与甲状腺激素受体（TR）亚型的对接亲和力相似且对GH3细胞有抑制作用，但仅在暴露于6PPD后，幼体斑马鱼的甲状腺信号通路、眼睛发育、趋光行为和视网膜层细胞密度受到显著影响。进一步研究表明，6PPD可作为TR拮抗剂，降低视蛋白丰度并抑制视锥光感受器细胞增殖，最终改变视网膜层结构并导致斑马鱼小眼症。特别是，在环境相关浓度暴露下，尽管未观察到明显的眼部组织病理学变化，但6PPD诱导了[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]基因表达的改变。本研究首次表明，与6PPDQ相比，6PPD对视觉系统的损害更严重，甲状腺信号通路紊乱是一个促成因素，而其他重要的毒性靶点仍需进一步研究。
