利用幼体斑马鱼的神经行为测定法测定麻醉效力。
Determination of narcotic potency using a neurobehavioral assay with larval zebrafish.
机构信息
The Procter & Gamble Company, Cincinnati, OH, USA.
Department of Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory, and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, USA.
出版信息
Neurotoxicology. 2019 Sep;74:67-73. doi: 10.1016/j.neuro.2019.05.005. Epub 2019 May 11.
BACKGROUND
Identifying chemicals with narcotic potency is an important aspect of assessing the safety of consumer products that may be accidentally ingested. A rapid and efficient assay of narcotic potency is desired for assessing chemicals with such suspected activity.
OBJECTIVES
This purpose of this research was to develop a non-mammalian vertebrate, high throughput, neurobehavioral method to assess the narcotic potency of chemicals using larval zebrafish.
METHODS
Larval zebrafish were acutely exposed to chemicals beginning at 5 days post fertilization (5 dpf). Locomotor activity, elicited by regular, periodic photostimulation, was quantified using a video tracking apparatus. Narcotic potency was determined as the molar concentration at which photostimulated locomotor activity was reduced by 50% (IC). Toxicity was assessed based on observations of morbidity or mortality. Recovery was assessed following removal of test material by serial dilution and reassessment of photostimulated behavior 24 hr later (6 dpf).
RESULTS
A total of 21 chemicals were assessed. Etomidate, a human narcotic analgesic agent, was used as a reference material. Investigating a series of eleven linear, primary alcohols (C6 to C16), a relationship between narcotic potency and carbon number was observed; narcotic potency increased with carbon number up to C12, consistent with historical studies. For a set of technical grade surfactants, nonionic surfactants (i.e., alcohol ethoxylates) were observed to be narcotic agents while anionic surfactants produced evidence of reduced locomotor activity only in combination with toxicity. Of the solvents evaluated, only ethanol exhibited narcotic activity with an IC of 261 mM and was the least potent of the chemicals investigated. Etomidate was the most potent material evaluated with an IC of 0.39 μM.
CONCLUSIONS
The larval zebrafish neurobehavioral assay provides a method capable of estimating the narcotic potency of chemicals and can identify if toxicity contributes to observed neurobehavioral effects in the test organism.
背景
识别具有麻醉效力的化学物质是评估可能意外摄入的消费品安全性的一个重要方面。对于评估具有这种可疑活性的化学物质，需要一种快速有效的麻醉效力测定方法。
目的
本研究的目的是开发一种非哺乳动物脊椎动物、高通量的神经行为方法，使用幼鱼斑马鱼来评估化学物质的麻醉效力。
方法
幼鱼斑马鱼从受精后 5 天（5 dpf）开始急性暴露于化学物质。使用视频跟踪装置定量测定由定期、周期性光刺激引发的运动活性。麻醉效力以光刺激运动活性降低 50%（IC）时的摩尔浓度来确定。根据发病率或死亡率观察评估毒性。通过连续稀释去除测试材料，并在 24 小时后（6 dpf）重新评估光刺激行为，评估恢复情况。
结果
共评估了 21 种化学物质。依托咪酯，一种人类麻醉镇痛药，被用作参考物质。研究了一系列 11 种线性、伯醇（C6 至 C16），观察到麻醉效力与碳数之间存在关系；麻醉效力随碳数增加至 C12 而增加，与历史研究一致。对于一系列技术级表面活性剂，观察到非离子表面活性剂（即醇乙氧基化物）是麻醉剂，而阴离子表面活性剂仅在与毒性结合时才表现出运动活性降低的证据。在所评估的溶剂中，只有乙醇表现出麻醉活性，IC 为 261mM，是所研究的化学物质中最不活跃的。依托咪酯是评估的最有效物质，IC 为 0.39 μM。
结论
幼鱼斑马鱼神经行为测定法提供了一种能够估计化学物质麻醉效力的方法，并可以确定毒性是否导致测试生物中观察到的神经行为效应。
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