Basnet Ram Manohar, Guarienti Michela, Memo Maurizio
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa, 11, 25123 Brescia, Italy.
Int J Mol Sci. 2017 Mar 9;18(3):596. doi: 10.3390/ijms18030596.
Zebrafish embryo is emerging as an important tool for behavior analysis as well as toxicity testing. In this study, we compared the effect of nine different methylxanthine drugs using zebrafish embryo as a model. We performed behavioral analysis, biochemical assay and Fish Embryo Toxicity (FET) test in zebrafish embryos after treatment with methylxanthines. Each drug appeared to behave in different ways and showed a distinct pattern of results. Embryos treated with seven out of nine methylxanthines exhibited epileptic-like pattern of movements, the severity of which varied with drugs and doses used. Cyclic AMP measurement showed that, despite of a significant increase in cAMP with some compounds, it was unrelated to the observed movement behavior changes. FET test showed a different pattern of toxicity with different methylxanthines. Each drug could be distinguished from the other based on its effect on mortality, morphological defects and teratogenic effects. In addition, there was a strong positive correlation between the toxic doses (TC) calculated in zebrafish embryos and lethal doses (LD) in rodents obtained from TOXNET database. Taken together, all these findings elucidate the potentiality of zebrafish embryos as an in vivo model for behavioral and toxicity testing of methylxanthines and other related compounds.
斑马鱼胚胎正成为行为分析以及毒性测试的一种重要工具。在本研究中，我们以斑马鱼胚胎为模型，比较了九种不同甲基黄嘌呤药物的效果。在用甲基黄嘌呤处理斑马鱼胚胎后，我们对其进行了行为分析、生化测定和鱼类胚胎毒性（FET）测试。每种药物的表现似乎都不同，且呈现出独特的结果模式。九种甲基黄嘌呤中的七种处理后的胚胎表现出癫痫样的运动模式，其严重程度因药物和使用剂量而异。环磷酸腺苷（cAMP）测量显示，尽管某些化合物使cAMP显著增加，但这与观察到的运动行为变化无关。FET测试显示不同甲基黄嘌呤具有不同的毒性模式。每种药物可根据其对死亡率、形态缺陷和致畸作用的影响与其他药物区分开来。此外，在斑马鱼胚胎中计算出的毒性剂量（TC）与从TOXNET数据库获得的啮齿动物致死剂量（LD）之间存在很强的正相关。综上所述，所有这些发现阐明了斑马鱼胚胎作为甲基黄嘌呤和其他相关化合物行为和毒性测试体内模型的潜力。
