Division of Electronics Engineering and Research Center for Intelligent Robots, Chonbuk National University, Jeonju 54896, Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828, Korea.
Int J Mol Sci. 2019 Apr 8;20(7):1725. doi: 10.3390/ijms20071725.
Cell cytotoxicity assays, such as cell viability and lactate dehydrogenase (LDH) activity assays, play an important role in toxicological studies of pharmaceutical compounds. However, precise modeling for cytotoxicity studies is essential for successful drug discovery. The aim of our study was to develop a computational modeling that is capable of performing precise prediction, processing, and data representation of cell cytotoxicity. For this, we investigated protective effect of quercetin against various mycotoxins (MTXs), including citrinin (CTN), patulin (PAT), and zearalenol (ZEAR) in four different human cancer cell lines (HeLa, PC-3, Hep G2, and SK-N-MC) in vitro. In addition, the protective effect of quercetin (QCT) against various MTXs was verified via modeling of their nonlinear protective functions using artificial neural networks. The protective model of QCT is built precisely via learning of sparsely measured experimental data by the artificial neural networks (ANNs). The neuromodel revealed that QCT pretreatment at doses of 7.5 to 20 μg/mL significantly attenuated MTX-induced alteration of the cell viability and the LDH activity on HeLa, PC-3, Hep G2, and SK-N-MC cell lines. It has shown that the neuromodel can be used to predict the protective effect of QCT against MTX-induced cytotoxicity for the measurement of percentage (%) of inhibition, cell viability, and LDH activity of MTXs.
细胞毒性检测,如细胞活力和乳酸脱氢酶(LDH)活性检测,在药物化合物的毒理学研究中起着重要作用。然而,对于细胞毒性研究来说,精确的建模是成功发现药物的关键。我们的研究旨在开发一种能够精确预测、处理和数据表示细胞毒性的计算模型。为此,我们研究了槲皮素对各种霉菌毒素(MTXs)的保护作用,包括桔青霉素(CTN)、棒曲霉素(PAT)和玉米赤霉烯酮(ZEAR),在四种不同的人癌细胞系(HeLa、PC-3、Hep G2 和 SK-N-MC)体外。此外,还通过使用人工神经网络对各种 MTXs 的非线性保护功能进行建模,验证了槲皮素(QCT)的保护作用。通过人工神经网络(ANNs)对稀疏测量的实验数据进行学习,精确地构建了 QCT 的保护模型。神经模型表明,QCT 预处理剂量为 7.5 至 20 μg/mL 时,可显著减弱 MTX 诱导的 HeLa、PC-3、Hep G2 和 SK-N-MC 细胞系的细胞活力和 LDH 活性变化。该神经模型可用于预测 QCT 对 MTX 诱导的细胞毒性的保护作用,用于测量 MTXs 的抑制百分比(%)、细胞活力和 LDH 活性。