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首页> 外文期刊>Journal of biomolecular screening: The official journal of the Society for Biomolecular Screening >High-content imaging technology for the evaluation of drug-induced steatosis using a multiparametric cell-based assay
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High-content imaging technology for the evaluation of drug-induced steatosis using a multiparametric cell-based assay

机译：高内涵成像技术，用于基于多参数细胞的评估药物诱导的脂肪变性

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In the present study, we developed a cell-based protocol for the identification of drugs able to induce steatosis. The assay measures multiple markers of toxicity in a 96-well plate format using high-content screening (HCS) technology. After treating HepG2 cells with increasing concentrations of the tested compounds, toxicity parameters were analyzed using fluorescent probes: BODIPY493/503 (lipid content), 2′,7′-dihydrodichlorofluorescein diacetate (reactive oxygen species [ROS] generation), tetramethyl rhodamine methyl ester (mitochondrial membrane potential), propidium iodide (cell viability), and Hoechst 33342 (nuclei staining). A total of 16 drugs previously reported to induce liver steatosis through different mechanisms (positive controls) and six nonsteatotic compounds (negative controls) were included in the study. All the steatosis-positive compounds significantly increased BODIPY493/503 fluorescence in HepG2 cells, whereas none of the negative controls induced lipid accumulation. In addition to effects on fat levels, increased ROS generation was produced by certain compounds, which could be indicative of increased risk of liver damage. Our results suggest that this in vitro approach is a simple, rapid, and sensitive screening tool for steatosis-inducing drugs. This conclusion should be confirmed by testing a larger number of steatosis-positive and -negative inducers.
机译：在本研究中，我们开发了一种基于细胞的方案，用于鉴定能够诱导脂肪变性的药物。该测定法使用高含量筛选（HCS）技术以96孔板的形式测量多种毒性标记物。用递增浓度的测试化合物处理HepG2细胞后，使用荧光探针分析了毒性参数：BODIPY493 / 503（脂质含量），2'，7'-二氢二氯荧光素二乙酸盐（反应性氧[ROS]生成），四甲基若丹明甲酯（线粒体膜电位），碘化丙锭（细胞活力）和Hoechst 33342（核染色）。总共报道了以前报道的通过不同机制诱导肝脂肪变性的16种药物（阳性对照）和6种非脂肪变性化合物（阴性对照）。所有脂肪变性阳性化合物均显着增加HepG2细胞的BODIPY493 / 503荧光，而阴性对照均未诱导脂质蓄积。除了对脂肪水平的影响外，某些化合物还增加了ROS的产生，这可能表明肝损害的风险增加。我们的结果表明，这种体外方法是诱导脂肪变性的药物的简单，快速和敏感的筛选工具。该结论应通过测试大量脂肪变性阳性和阴性诱导剂来证实。

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