Lee Dong Woo, Lee Moo-Yeal, Koh Sukkil, Yang Mihi
Department of Biomedical Engineering, Konyang University, Daejeon 35365, Korea.
Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH 44115-2214, USA.
Micromachines (Basel). 2020 Oct 3;11(10):922. doi: 10.3390/mi11100922.
A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear () extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC values. The IC value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (s < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells.
一种带有三维培养肝细胞的微柱/微孔芯片平台已被用于对双酚A（BPA）——一种内分泌干扰化学物质——的肝毒性进行高通量筛选。我们之前发现，酒精脱氢酶（ADH）和乙醛脱氢酶2（ALDH2）可减轻双酚A的肝毒性。在本研究中，我们在带有人类肝细胞的微柱/微孔芯片平台上，测试了用韩国梨（）提取物、ADH和ALDH的刺激剂以及梨中的参考化合物熊果苷对双酚A进行潜在解毒的效果。令人惊讶的是，在韩国梨提取物存在的情况下，双酚A的毒性降低，这表现为半数抑制浓度（IC）值显著增加。用韩国梨提取物测试时，针对HepG2细胞的双酚A的IC值从151 μM变为451 μM，而针对Hep3B细胞测试时，IC值从110 μM变为204 μM。在测试的不同浓度中，1.25、2.5和5 mg/mL的提取物显著降低了双酚A的毒性（P < 0.05）。然而，熊果苷没有这种解毒作用。肝细胞中ADH蛋白水平的变化支持了这一结果。
