Morphological and behavioral responses of zebrafish after 24 h of ketamine embryonic exposure
Morphological and behavioral responses of zebrafish after 24 h of ketamine embryonic exposure
复制标题
DOI：
10.1016/j.taap.2017.02.013
复制
发表时间：
2017-04-15
影响因子：
3.8
通讯作者：
Coimbra, Ana M.
中科院分区：
文献类型：
--
作者：
Felix, Luis M.;Serafim, Cindy;Coimbra, Ana M.
在淡水和海洋生态系统中都发现了氯胺酮，这是一种用作非法药物的麻醉剂。然而，关于其对水生生物的影响的知识仍然有限。本研究旨在通过分析其时间和剂量依赖性发育毒性和长期行为变化来测试其在斑马鱼胚胎中的作用。使用概率单位分析，根据存活百分比计算24 h-LC 50。根据24 h-LC 50（94.4 mg L-1），将胚胎（受精后2小时-hpf）分为4组，包括对照组，并暴露于50、70或90 mg L-1氯胺酮浓度24 h。在实验期的过程中评价发育参数，并在144 hpf下分析解剖异常和运动缺陷。尽管在最低暴露组中转移到胚胎中的氯胺酮比例较高（每个胚胎约为0.056 +/- 0.020 pmol），但结果表明，死亡率增加、水肿、心率改变、畸形和异常生长率等终点受到显著影响。在144 hpf时，发育异常包括暴露于70和90 mg L-1的组中的胸部和躯干异常。软骨（阿辛蓝）和骨（钙黄绿素）元素的缺陷也证实了所观察到的颅面异常。qRT-PCR检测到8 hpf时发育相关基因nog 3显著上调。早期暴露于氯胺酮也会导致长期的行为变化，例如在144 hpf时趋触性增加和回避行为中断。总之，本研究提供了关于氯胺酮致畸潜力的新证据，表明氯胺酮在水生环境中可能具有药理学影响。(C)2017爱思唯尔公司All rights reserved.
Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24 h-LC50 was calculated from percent survival using probit analysis. Based on the 24 h-LC50 (94.4 mg L-1), embryos (2 hour post-fertilization -hpf) were divided into four groups, including control, and exposed for 24 h to ketamine concentrations of 50, 70 or 90 mg L-1. Developmental parameters were evaluated on the course of the experimental period, and anatomical abnormalities and locomotor deficits were analyzed at 144 hpf. Although the portion of ketamine transferred into the embryo was higher in the lowest exposed group (about 0.056 +/- 0.020 pmol per embryo), the results showed that endpoints such as increased mortality, edema, heart rate alterations, malformation and abnormal growth rates were significantly affected. At 144 hpf, the developmental abnormalities included thoracic and trunk abnormalities in the groups exposed to 70 and 90 mg L-1. Defects in cartilage (alcian blue) and bone (calcein) elements also corroborated the craniofacial anomalies observed. A significant up-regulation of the development-related gene nog3 was detected by qRT-PCR at 8 hpf. Early exposure to ketamine also resulted in long-term behavioral changes, such as an increase in thigmotaxis and disruption of avoidance behavior at 144 hpf. Altogether, this study provides new evidence on the ketamine teratogenic potential, indicating a possible pharmacological impact of ketamine in aquatic environments. (C) 2017 Elsevier Inc. All rights reserved.