Center for Water and Ecology, State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.
Center for Water and Ecology, State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.
Sci Total Environ. 2024 Jan 15;908:168043. doi: 10.1016/j.scitotenv.2023.168043. Epub 2023 Oct 26.
Pharmaceutical transformation products (TPs) generated during wastewater treatment have become an environmental concern. However, there is limited understanding regarding the TPs produced from pharmaceuticals during wastewater treatment. In this study, chloroquine (CQ), which was extensively used for treating coronavirus disease-19 (COVID-19) infections during the pandemic, was selected for research. We identified and fractionated the main TP produced from CQ during chlorine disinfection and investigated the neurotoxic effects of CQ and its main TP on zebrafish (Danio rerio) embryos. Halogenated TP353 was observed as one of the main TPs produced from CQ during chlorine disinfection. Zebrafish embryos test revealed that TP353 caused higher neurotoxicity in zebrafish larvae, as compared to the CQ, and that was accompanied by significantly decreased expression levels of the genes related to central nervous system development (e.g., gfap, syn2a, and elavl3), inhibited activity of acetylcholinesterase (AChE), reduced GFP fluorescence intensity of motor neuron axons in transgenic larvae (hb9-GFP), and reduced total swimming distance and swimming velocity of larvae during light-dark transition stimulation. The results of this study can potentially be utilized as a theoretical reference for future evaluations of environmental risks associated with CQ and its related TPs. This work presents a methodology for assessing the environmental hazards linked to the discharge of pharmaceutical TPs after wastewater treatment.
制药转化产物（TPs）在废水处理过程中产生，已成为环境关注的焦点。然而，对于在废水处理过程中由药物产生的 TPs，人们的了解有限。在这项研究中，选择了氯喹（CQ）进行研究，氯喹在大流行期间被广泛用于治疗冠状病毒病-19（COVID-19）感染。我们鉴定并分馏了 CQ 在氯消毒过程中产生的主要 TP，并研究了 CQ 及其主要 TP 对斑马鱼（Danio rerio）胚胎的神经毒性作用。在氯消毒过程中，观察到卤代 TP353 是 CQ 产生的主要 TP 之一。斑马鱼胚胎试验表明，与 CQ 相比，TP353 对斑马鱼幼虫的神经毒性更高，并且伴随着与中枢神经系统发育相关的基因表达水平显著降低（例如，gfap、syn2a 和 elavl3），乙酰胆碱酯酶（AChE）活性受到抑制，转基因幼虫（hb9-GFP）运动神经元轴突的 GFP 荧光强度降低，以及幼虫在明暗转换刺激期间的总游泳距离和游泳速度降低。本研究的结果可作为未来评估 CQ 及其相关 TPs 相关环境风险的理论参考。这项工作提出了一种评估与废水处理后药物 TPs 排放相关的环境危害的方法。
