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Potency ranking of valproic acid analogues as to inhibition of cardiac differentiation of embryonic stem cells in comparison to their in vivo embryotoxicity.

机译:丙戊酸类似物相对于其体内胚胎毒性的抑制胚胎干细胞心脏分化的能力排名。

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摘要

The embryonic stem cell test (EST) is one of the more promising and extensively studied tests in the field of developmental toxicology. We evaluated the effect of a series of structurally related valproic acid analogues on cardiomyocyte differentiation in the EST. The goal of the present study was to determine the applicability of the EST by potency ranking within this chemical class. Cardiomyocyte differentiation was evaluated by morphological scoring as well as by gene expression analysis of cardiac markers using RT-PCR. All VPA analogues tested inhibited cardiomyocyte differentiation, with the exception of (+/-)-2-ethyl-4-methyl pentanoic acid, which correlates to their known in vivo developmental toxicity. Effects were also evident on gene expression of cardiomyocyte differentiation-regulated genes, such as MHC and Nkx2.5. Overall, the present results indicate that the assay can be a valuable screening tool in potency ranking of structurally related compounds.
机译:胚胎干细胞测试(EST)是发育毒理学领域中最有前途且经过广泛研究的测试之一。我们评估了EST中一系列结构相关的丙戊酸类似物对心肌细胞分化的影响。本研究的目的是通过在该化学类别内的效能排名来确定EST的适用性。通过形态学评分以及通过使用RT-PCR的心脏标志物的基因表达分析来评估心肌细胞的分化。除(+/-)-2-乙基-4-甲基戊酸外,所有测试的VPA类似物均抑制心肌细胞分化,这与其已知的体内发育毒性有关。对心肌细胞分化调节基因如MHC和Nkx2.5的基因表达也有明显影响。总体而言,目前的结果表明该测定法可以作为结构相关化合物效能分级的有价值的筛选工具。

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