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集中的神经活性药物混合物和改变的神经递质水平在暴露于废水的鱼的大脑中。

Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent.

机构信息

School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.

Biosciences, College of Life & Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK.

出版信息

Sci Total Environ. 2018 Apr 15;621:782-790. doi: 10.1016/j.scitotenv.2017.11.265. Epub 2017 Dec 1.

DOI:10.1016/j.scitotenv.2017.11.265
PMID:29202289
Abstract

Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were between 3-40 fold higher in brain compared with blood plasma, showing these neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for the potential for any adverse ecotoxicological effects, the effect ratio was calculated from human therapeutic plasma concentrations (HtPCs) and the measured or predicted fish plasma concentrations of pharmaceuticals. After accounting for a safety factor of 1000, the effect ratios indicated that fluoxetine, norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk assessment studies. Furthermore, although plasma concentrations of all the pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in serotonin, glutamate, acetylcholine and tryptophan concentrations were observed in different brain regions of effluent-exposed fish. This study highlights the importance of determining the potential health effects arising from the concentration of complex environmental mixtures in risk assessment studies.

摘要

鱼类可能通过污水处理厂的污水排放接触到各种神经活性药物,并对鱼类的行为和生态产生潜在影响,这引起了人们的关注。在这项研究中,我们研究了 14 种神经活性药物在经过 15 天暴露后,从处理后的污水废水中进入罗非鱼(Rutilus rutilus)血浆和大脑区域的情况。我们表明,包括 6 种选择性 5-羟色胺再摄取抑制剂、1 种 5-羟色胺-去甲肾上腺素再摄取抑制剂、3 种非典型抗精神病药、2 种三环抗抑郁药和 1 种苯二氮䓬类药物在内的复杂药物混合物集中在大脑的不同区域,包括脑的端脑、下丘脑、视顶盖和后脑。除了去甲西泮外,暴露于污水的鱼类大脑中的药物浓度是血浆中的 3-40 倍,这表明这些神经活性药物很容易被鱼类吸收到脑组织中。为了评估潜在的不利生态毒理学影响,我们根据人类治疗血浆浓度(HtPC)和测量或预测的鱼类血浆药物浓度计算了效应比。在考虑了 1000 的安全系数后,效应比表明氟西汀、去甲氟西汀、舍曲林和阿米替林需要优先进行风险评估研究。此外,尽管所有药物的血浆浓度均低于 HtPC 的 33-5714 倍,但在暴露于污水的鱼类的不同大脑区域观察到了 5-羟色胺、谷氨酸、乙酰胆碱和色氨酸浓度的变化。这项研究强调了在风险评估研究中确定复杂环境混合物浓度引起的潜在健康影响的重要性。

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