文献类型： 外文期刊
作者： Jiao, Fang 1 ; Zhao, Yang 2 ; Yue, Qiang 3 ; Wang, Qi 4 ; Li, Zhongzhi 1 ; Lin, Wanjing 1 ; Han, Lingxi 3 ; Wei, Liangfu 1 ;
作者机构： 1.South China Agr Univ, Coll Marine Sci, Guangzhou 510640, Peoples R China
2.Zhejiang Acad Agr Sci, Hangzhou 310058, Peoples R China
3.Shaoguan Univ, Guangdong Prov Key Lab Utilizat & Conservat Food &, Shaoguan 512005, Peoples R China
4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China
5.Qingdao Agr Univ, Coll Hort, Qingdao 266109, Peoples R China
6.Guangdong Hong Kong Joint Lab Water Secur, Zhuhai 519087, Peoples R China
7.Xiamen Key Lab Intelligent Fishery, Xiamen 361100, Peoples R China
关键词： 6PPD; 6PPDQ; Hepatotoxicity; PPARg; zebrafish
期刊名称：ENVIRONMENTAL SCIENCE AND ECOTECHNOLOGY （ 影响因子：14.3； 五年影响因子：15.0 ）
ISSN： 2666-4984
年卷期： 2025 年 25 卷
页码：
收录情况： SCI
摘要： N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidation derivative, 6PPD-quinone (6PPDQ), have been extensively detected in environmental and biological samples, raising significant concerns regarding their chronic aquatic toxicity at environmentally relevant concentrations. However, the underlying mechanisms driving this chronic toxicity remain largely unexplored. Here we show that zebrafish exposed to 6PPD and 6PPDQ exhibit distinct toxicokinetic profiles, with 6PPD preferentially accumulating in the liver and 6PPDQ predominantly targeting the brain. Exposure to both compounds impaired zebrafish growth, induced hepatic damage, and disrupted locomotor behavior. Transcriptomic analysis of liver tissue revealed disturbances in lipid and carbohydrate metabolic pathways in both treatment groups, with distinct differences in gene expression patterns and biochemical responses between 6PPD and 6PPDQ. Specifically, both compounds downregulated peroxisome proliferator-activated receptor gamma (PPARg) and elevated the expression of pro-inflammatory cytokines (TNF-a and IL-6). Molecular dynamics simulations and surface plasmon resonance experiments further demonstrated that hepatotoxicity was associated with direct binding of these compounds to PPARg, a critical regulator of lipid metabolism and inflammation. Our findings highlight the hepatotoxic risks of 6PPD and 6PPDQ to aquatic life. Importantly, 6PPDQ exhibited greater toxicity compared to 6PPD, emphasizing an urgent need for targeted environmental controls and regulatory actions to mitigate ecological harm and potential public health consequences. (c) 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Society for Environmental Sciences, Harbin Institute of Technology, Chinese Research Academy of Environmental Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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