Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test
Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test
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DOI：
10.1016/j.reprotox.2012.02.007
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发表时间：
2012-08-01
影响因子：
3.3
通讯作者：
Oskarsson, Agneta
中科院分区：
文献类型：
--
作者：
Mattsson, Anna;Ulleras, Erik;Oskarsson, Agneta
斑马鱼胚胎毒性试验此前已与外部代谢激活系统(MAS)相结合，以评估母体代谢产生的代谢物的发育毒性。由于MAS的毒性，暴露被限制在一个早期和短期内。我们已经修改了方法，并增加了更多的测试时间点，延长了暴露时间。以驱虫药阿苯达唑为模型物质，在斑马鱼胚胎发育的3个窗口期，即受精后2~3、12~14和24~28h，验证了毒性效应的阶段性，表明MAS通过代谢失活降低了各时间点的毒性。化学分析证实，阿苯达唑能被MAS有效地代谢成对斑马鱼胚胎无毒的亚硫醚和砜。综上所述，改良的斑马鱼胚胎毒性试验MAS可扩展用于不同发育阶段代谢物的检测。(C)2012 Elsevier Inc.保留所有权利。
The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28 h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages. (C) 2012 Elsevier Inc. All rights reserved.