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首页> 外文期刊>Pigment cell research >Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds
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Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds

机译：斑马鱼作为基于表型的黑色素调节化合物筛选的新模型

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摘要

Although many hypo-pigmenting agents are currently available, the demand for novel whitening agents is increasing, in part due to the weak effectiveness and unwanted side effects of currently available compounds. To screen for novel hypo-pigmenting agents, many methodologies such as cell culture and enzymatic assays are routinely used. However, these models have disadvantages in terms of physiological and economic relevance. In this study, we validated zebrafish as a whole-animal model for phenotype-based screening of melanogenic inhibitors or stimulators. We used both the wellknown melanogenic inhibitors (1-phenyl-2-thiourea, arbutin, kojic acid, 2-mercaptobenzothiazole) and newly developed small molecule compounds (haginin, YT16i). All the tested compounds produced inhibitory effects on the pigmentation of zebrafish, most likely due to their inhibitory potential on tyrosinase activity. In simultaneous in vivo toxicity tests, a newly developed melanogenic inhibitor YT16i showed massive abnormalities in terms of deformed morphologies and cardiac function. Together, these results provide a rationale in screening and evaluating the putative melanogenic regulatory compounds. We suggest that the zebrafish system is a novel alternative to mammalian models, with several advantages including the rapidity, cost-effectiveness, and physiological relevance.
机译：尽管当前可获得许多色素减退剂，但是对新型增白剂的需求正在增加，部分原因是目前可获得的化合物的功效弱和不希望的副作用。为了筛选新的色素减退剂，通常使用许多方法，例如细胞培养和酶促测定。但是，这些模型在生理和经济相关性方面都有缺点。在这项研究中，我们验证了斑马鱼作为一种基于动物表型的黑色素生成抑制剂或刺激物筛选的全动物模型。我们同时使用了著名的黑色素抑制剂（1-苯基-2-硫脲，熊果苷，曲酸，2-巯基苯并噻唑）和新开发的小分子化合物（haginin，YT16i）。所有测试的化合物都对斑马鱼的色素沉着产生抑制作用，这很可能是由于它们对酪氨酸酶活性的抑制作用。在同时进行的体内毒性测试中，新开发的黑色素生成抑制剂YT16i在形貌和心脏功能方面表现出巨大异常。总之，这些结果为筛选和评估假定的黑色素调节化合物提供了理论依据。我们建议斑马鱼系统是哺乳动物模型的新型替代品，具有快速，成本效益和生理相关性等多个优点。

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