The effect of zaleplon on metabolic changes in neurotransmitters and toxic effects in Danio fish

A. A. Volkova, Roman A. Kalekin, Alevtina Mikhailovna Orlova, A. Pavlova, Olga Genrikhovna Astashkina, Andrey L. Pavlov
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Abstract

Introduction. Z-drugs are a group of “non-benzodiazepine” drugs with the main mode of action regulating sleep behavior in humans through exposure to GABA receptors. There are reports indicating the toxic effects of overdose and abuse of zaleplon. However, information on the effect of Z-drugs on neurotransmitter levels is scarce. The aim of this study was to study the effect of zaleplon exposure on neurotransmitter levels in the larvae of Danio fish using targeted metabolomics. Material and methods. 4-hour exposure to zaleplon in concentrations of 0.1, 1.0, 10, 100 and 1000 μg/l was carried out on the larvae of Danio fish. Intervention groups were compared with control groups. Each group consisted of 20 larvae of Danio fish. Neurotransmitters and their metabolites were measured using high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). Results. Twenty-two metabolites associated with neurotransmission were quantified. Significantly increased metabolites were tryptophan, serotonin, 5-hydroxyindolacetic acid, acetylserotonin, epinephrine and choline. Significantly reduced metabolites were 5-hydroxytryptophan, 5-methoxytryptamine, dopamine, normetanephrine, metanephrine, kynurenine, 3-hydroxykinurenine, anthranilic acid and gamma-aminobutyric acid. Limitation. When studying metabolic changes in neurotransmitters and toxic effects in Danio fish, the results of a group of 20 larvae were analyzed, which is a sufficient sample to state the results obtained. Conclusion. Exposure to zaleplon caused metabolic changes in the concentrations of neurotransmitters associated with most major neurotransmitter systems.
扎来普隆对达尼欧鱼神经递质代谢变化及毒性作用的影响
介绍。z -drug是一类“非苯二氮卓类”药物,其主要作用方式是通过暴露于GABA受体来调节人类的睡眠行为。有报告指出,过量使用和滥用扎来普隆会产生毒性作用。然而,关于z -药物对神经递质水平的影响的信息很少。本研究的目的是利用靶向代谢组学方法研究扎来普隆暴露对达尼欧鱼幼鱼神经递质水平的影响。材料和方法。采用浓度分别为0.1、1.0、10、100和1000 μg/l的扎来普隆对达里奥鱼仔鱼进行4 h的暴露试验。将干预组与对照组进行比较。每组20尾达尼欧鱼幼鱼。采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定神经递质及其代谢物。结果。对22种与神经传递相关的代谢物进行了量化。代谢产物色氨酸、血清素、5-羟基吲哚乙酸、乙酰血清素、肾上腺素和胆碱显著增加。显著减少的代谢物有5-羟色氨酸、5-甲氧基色胺、多巴胺、去甲肾上腺素、去甲肾上腺素、犬尿氨酸、3-羟肌尿氨酸、邻氨基苯甲酸和γ -氨基丁酸。限制。在研究达尼欧鱼的神经递质代谢变化和毒性作用时,分析了一组20只幼虫的结果,这是一个足够的样本来说明所获得的结果。结论。暴露于扎来普隆引起与大多数主要神经递质系统相关的神经递质浓度的代谢变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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