Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds.

Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds.
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对斑马鱼幼虫的筛选揭示了十五种荧光化合物的组织特异性分布。

DOI:
10.1242/dmm.028811
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发表时间:
2017-09-01
影响因子:
4.3
通讯作者:
Wang X
Wang X
中科院分区:
医学2区
文献类型:
--
作者:
Yao Y;Sun S;Fei F;Wang J;Wang Y;Zhang R;Wu J;Liu L;Liu X;Cui Z;Li Q;Yu M;Dang Y;Wang X

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斑马鱼是用于低成本体内全生物体筛选的突出脊椎动物模型。在我们最近的荧光化合物在活斑马鱼幼虫的分布模式的筛选中,鉴定出具有组织特异性分布的15种化合物。观察到几种化合物在组织中蓄积,据报道它们会诱导副作用,具有相似结构的化合物往往富集在相同组织中,差异较小。特别是,我们发现了三种新的红色荧光骨染色染料:红紫素,lucidin和3-羟基-morindone;红紫素可以有效地标记骨骼在幼虫和成年斑马鱼,以及在出生后的小鼠,而不会显着影响骨量和密度。此外,观察到两种结构相似的化疗化合物,阿霉素和表阿霉素,在斑马鱼中具有不同的分布偏好。Epiraldehyde在肝脏中保持相对较高的浓度,并且在抑制由krasG 12 V过表达引起的肝脏增生方面表现更好。总之,我们的研究表明,透明的斑马鱼幼虫作为有价值的工具,用于识别组织特异性分布的荧光化合物。总结:15种荧光化合物在斑马鱼幼虫中具有组织特异性分布:三种蒽醌类被鉴定为活脊椎动物中的骨染料,两种化疗药物被证明对肝脏有明显的偏好。
The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds. Summary: Fifteen fluorescent compounds have tissue-specific distributions in zebrafish larvae: three anthraquinones were identified as bone dyes in live vertebrates, and two chemotherapeutic drugs were shown to have distinct preferences for the liver.
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