Wu Yuanzhao, Fan Fengjun, Zhou Lu, Shen Yihang, Wang Anli, Qin Yazhou, Wang Jiye, Yao Weixuan
Zhejiang Key Laboratory of Drug Prevention and Control Technology, The Department of Criminal Science and Technology, Zhejiang Police College, Hangzhou, 310051, Zhejiang, China.
National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Environ Res. 2025 Jul 1;276:121517. doi: 10.1016/j.envres.2025.121517. Epub 2025 Apr 1.
As an emerging pollutant, the synthetic cannabinoid N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is widely abused and frequently detected in metropolitan wastewater. However, its effect on aquatic organisms remains unexplored. In this study, embryonic and larval zebrafish were exposed to sublethal concentrations of ADB-FUBINACA to assess its toxic effects via behavioral, biochemical, and metabolomic analyses. The observed morphological defects included reduced heartbeat, shorter body length, spinal deformation, and pericardial edema. Transgenic zebrafish exhibited cardiac developmental defects and apoptosis, indicating that cardiotoxicity is associated with dysregulated gene expression. Impaired motor activity and disrupted neuronal development suggested neurotoxicity. Elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels indicate oxidative stress, whereas transcriptional changes in immune-related genes reflect a dysregulated inflammatory response. Metabolomic analyses revealed disruptions in pathways related to alanine, purine, and pyrimidine metabolism, and arginine biosynthesis, which correlated with oxidative damage, cardiotoxicity, and neurodevelopmental effects. In conclusion, ADB-FUBINACA induces developmental toxicity in zebrafish embryos via oxidative stress and metabolic disruption, highlighting the potential environmental risks posed by this emerging pollutant.
作为一种新兴污染物，合成大麻素N-(1-氨基-3,3-二甲基-1-氧代丁烷-2-基)-1-(4-氟苄基)-1H-吲唑-3-甲酰胺（ADB-FUBINACA）被广泛滥用，且在大城市废水中经常被检测到。然而，其对水生生物的影响仍未得到探索。在本研究中，将斑马鱼胚胎和幼体暴露于亚致死浓度的ADB-FUBINACA中，通过行为、生化和代谢组学分析来评估其毒性作用。观察到的形态缺陷包括心跳减缓、体长缩短、脊柱变形和心包水肿。转基因斑马鱼表现出心脏发育缺陷和细胞凋亡，表明心脏毒性与基因表达失调有关。运动活动受损和神经元发育紊乱提示神经毒性。活性氧（ROS）和丙二醛（MDA）水平升高表明存在氧化应激，而免疫相关基因的转录变化反映了炎症反应失调。代谢组学分析揭示了与丙氨酸、嘌呤和嘧啶代谢以及精氨酸生物合成相关的途径受到干扰，这与氧化损伤、心脏毒性和神经发育影响相关。总之，ADB-FUBINACA通过氧化应激和代谢紊乱在斑马鱼胚胎中诱导发育毒性，突出了这种新兴污染物所带来的潜在环境风险。
