Chanlin Fang, Shanshan Di, Caihong Wang, Qinglian Hu, Yuanxiang Jin
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jan;287:110062. doi: 10.1016/j.cbpc.2024.110062. Epub 2024 Oct 25.
The increasing release of tire-derived particles, particularly those containing N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), into the environment has raised concerns regarding their ecological impact. This study aims to elucidate the toxicological effects of 6PPD on the metabolism in early developmental stage of zebrafish. Larval zebrafish were exposed to 10 and 100 μg/L 6PPD, and some endpoints in biochemical parameters, gene expression, and metabolism were analyzed. The results showed that 6PPD exposure disrupted glucolipid metabolism in zebrafish larvae, evidenced by increased triglyceride (TG) levels and decreased glucose content. Nile red staining indicated significant lipid accumulation in the liver and intestines. Additionally, RT-qPCR analysis revealed the upregulation of genes involved in lipid synthesis and metabolism, such as ppar-γ and fas, and downregulation of glycolysis-related genes like pk and gk. Furthermore, the untargeted metabolomics technique was used to identify a total of 220 differentially expressed metabolites (DEMs) with changes in amino acid metabolism, lipid metabolism, and the TCA cycle. KEGG pathway enrichment analysis highlighted disruptions mainly in Taurine and hypotaurine metabolism, Arginine and proline metabolism, and Histidine metabolism, which played very important roles on energy metabolism in zebrafish. The results provided some critical insights into the ecological risks associated with 6PPD.
轮胎衍生颗粒，尤其是含有N-（1,3-二甲基丁基）-N'-苯基-对苯二胺（6PPD）的颗粒，向环境中的释放量不断增加，引发了人们对其生态影响的担忧。本研究旨在阐明6PPD对斑马鱼早期发育阶段新陈代谢的毒理学效应。将斑马鱼幼体暴露于10和100μg/L的6PPD中，并分析了生化参数、基因表达和新陈代谢方面的一些指标。结果表明，暴露于6PPD会扰乱斑马鱼幼体的糖脂代谢，甘油三酯（TG）水平升高和葡萄糖含量降低证明了这一点。尼罗红染色表明肝脏和肠道中有明显的脂质积累。此外，RT-qPCR分析显示参与脂质合成和代谢的基因如ppar-γ和fas上调，而糖酵解相关基因如pk和gk下调。此外，采用非靶向代谢组学技术共鉴定出220种差异表达代谢物（DEM），其在氨基酸代谢、脂质代谢和三羧酸循环方面发生了变化。KEGG通路富集分析突出显示主要在牛磺酸和亚牛磺酸代谢、精氨酸和脯氨酸代谢以及组氨酸代谢方面存在紊乱，这些代谢在斑马鱼的能量代谢中起着非常重要的作用。这些结果为与6PPD相关的生态风险提供了一些关键见解。
