Romero-Alfano Irene, Prats Eva, Raldúa Demetrio, Blazquez Mercedes, Tauler Romà, Piña Benjamí, Gómez-Canela Cristian, Barata Carlos
Institute for Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona 18, Barcelona, 08034, Spain; Department of Analytical and Applied Chemistry, School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, Barcelona, 08017, Spain.
Research and Development Center (CID-CSIC), Jordi Girona, 18, Barcelona, 08034, Spain.
Chemosphere. 2025 Sep;385:144541. doi: 10.1016/j.chemosphere.2025.144541. Epub 2025 Jun 27.
Pharmaceutical residues in surface waters are an emerging environmental and public health issue, yet their biological impacts on aquatic life remain poorly understood. This study presents a cost-effective bioanalytical framework using Daphnia magna juveniles and zebrafish (Danio rerio) embryos to evaluate neurotoxic and cardiotoxic effects of pharmaceutical mixtures in rivers downstream of wastewater treatment plant (WWTP) effluents. Water samples from three rivers in north-eastern Spain (Besòs, Llobregat, and Onyar) were concentrated up to 5- and 20-fold using solid-phase extraction. Bioassays were conducted over 24 h for D. magna and five days for zebrafish embryos. Eighty pharmaceutical compounds were quantified via HPLC-MS and linked with phenotypic endpoints including locomotion, feeding, heart rate, neurotransmitter profiles, and metabolomic alterations. Of the 28 concentrated extracts, four were acutely toxic to zebrafish embryos. Altered behavioral and cardiovascular responses were observed in 22.2 % (D. magna) and 35.1 % (D. rerio) of extracts, primarily at higher enrichment. Concentrations of 31 pharmaceuticals were statistically associated with observed effects. Neuroactive drugs such as topiramate, rasagiline, citalopram, and fluvoxamine showed strong correlations with altered neurotransmitter levels in zebrafish, consistent with their known mechanisms. Seven additional compounds with secondary neuroactive properties were linked to similar neurological disruptions. Seventeen pharmaceuticals were associated with disturbances in amino acid metabolism and urea cycle pathways, indicating broader metabolic dysregulation. Overall, nearly 75 % of river extracts showed no observable effect, but several samples were acutely toxic or induced sublethal neurobehavioral and metabolic responses. These findings support the utility of D. magna and zebrafish (D. rerio) embryos as sensitive and complementary biosentinels for monitoring pharmaceutical pollution and highlight zebrafish as a relevant model for studying environmentally driven neurotoxicity with potential human health implications.
地表水中的药物残留是一个新出现的环境和公共卫生问题，然而它们对水生生物的生物学影响仍知之甚少。本研究提出了一个具有成本效益的生物分析框架，使用大型溞幼体和斑马鱼（Danio rerio）胚胎来评估污水处理厂（WWTP）废水排放下游河流中药物混合物的神经毒性和心脏毒性作用。西班牙东北部三条河流（贝索斯河、略夫雷加特河和奥尼亚尔河）的水样通过固相萃取浓缩了5倍和20倍。对大型溞进行了24小时的生物测定，对斑马鱼胚胎进行了五天的生物测定。通过HPLC-MS对80种药物化合物进行了定量，并将其与包括运动、摄食、心率、神经递质谱和代谢组学改变在内的表型终点联系起来。在28种浓缩提取物中，有4种对斑马鱼胚胎具有急性毒性。在22.2%（大型溞）和35.1%（斑马鱼）的提取物中观察到行为和心血管反应改变，主要是在富集程度较高时。31种药物的浓度与观察到的效应具有统计学相关性。托吡酯、雷沙吉兰、西酞普兰和氟伏沙明等神经活性药物与斑马鱼神经递质水平改变显示出强烈相关性，与其已知机制一致。另外七种具有次要神经活性特性的化合物与类似的神经功能障碍有关。17种药物与氨基酸代谢和尿素循环途径的紊乱有关，表明存在更广泛的代谢失调。总体而言，近75%的河流提取物没有观察到明显影响，但有几个样品具有急性毒性或诱导了亚致死性神经行为和代谢反应。这些发现支持了大型溞和斑马鱼（Danio rerio）胚胎作为监测药物污染的敏感和互补生物哨兵的实用性，并突出了斑马鱼作为研究具有潜在人类健康影响的环境驱动神经毒性的相关模型。
