Novel psychoactive substances (NPS), such as Esketamine (Esket), often contaminate the aquatic ecosystems following human consumption, raising concerns about the residues and potential ecological hazards to non-target organisms. The study used zebrafish as a model organism to investigate the developmental toxicity and ecotoxicological effects of acute Esket exposure. Our findings demonstrate that exposure to Esket significantly affected the early development and angiogenesis of zebrafish embryos/larvae. The mandible length was significantly decreased, and the angles between the pharyngeal arch cartilages were narrowed compared to the control group (all P < 0.05). Additionally, Esket resulted in a decrease of 47.6–89.8 % in the number of neural crest cells (NCC). Transcriptome analysis indicated altered expression of genes associated with cartilage and osteoblast growth. Moreover, Esket significantly inhibited swimming ability in zebrafish larvae and was accompanied by behavioral abnormalities and molecular alterations in the brain. Potential mechanisms underlying Esket-induced behavioral disorders involve neurotransmitter system impairment, abnormal cartilage development and function, aberrant vascular development, as well as perturbations in oxidative stress and apoptosis signaling pathways. Notably, the dysregulation of skeleton development through the bone morphogenetic protein (BMP) signaling pathway is identified as the primary mechanistic behind Esket-induced behavioral disorder. This study enhances our understanding of Esket's ecotoxicology profile and provides a comprehensive assessment of the environmental risks associated with NPS.

中文翻译：

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新型精神活性物质艾氯胺酮的生态毒理学风险评估：强调鱼类骨骼、行为和血管发育


艾氯胺酮 （Esket） 等新型精神活性物质 （NPS） 在人类食用后通常会污染水生生态系统，引发人们对其残留物和对非目标生物的潜在生态危害的担忧。该研究使用斑马鱼作为模式生物来研究急性 Esket 暴露的发育毒性和生态毒理学影响。我们的研究结果表明，暴露于 Esket 显着影响斑马鱼胚胎/幼虫的早期发育和血管生成。与对照组相比，下颌骨长度明显减少，咽弓软骨之间的角度变窄 （P均 < 0.05）。此外，Esket 导致神经嵴细胞 （NCC） 的数量减少了 47.6-89.8%。转录组分析表明与软骨和成骨细胞生长相关的基因表达发生改变。此外，Esket 显着抑制斑马鱼幼虫的游泳能力，并伴有大脑行为异常和分子改变。Esket 诱导的行为障碍的潜在机制包括神经递质系统损伤、软骨发育和功能异常、血管发育异常以及氧化应激和细胞凋亡信号通路的扰动。值得注意的是，通过骨形态发生蛋白 （BMP） 信号通路对骨骼发育的失调被确定为 Esket 诱导的行为障碍背后的主要机制。这项研究增强了我们对 Esket 生态毒理学概况的理解，并提供了对与 NPS 相关的环境风险的全面评估。