Transwell-Grown HepG2 Cell Monolayers as In Vitro Permeability Model to Study Drug-Drug or Drug-Food Interactions
Transwell-Grown HepG2 Cell Monolayers as In Vitro Permeability Model to Study Drug-Drug or Drug-Food Interactions
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DOI：
10.1089/jmf.2010.0041
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发表时间：
2011-01-01
影响因子：
2.4
通讯作者：
Kristl, Albin
中科院分区：
文献类型：
--
作者：
Berginc, Katja;Kristl, Albin
HepG 2细胞单层，在胶原包被的Transwell（康宁公司，Corning，NY，USA）插入物，可用于评价食品补充剂与作为P-糖蛋白（Pgp）和/或多药耐药相关蛋白2（MRP-2）的底物的药物之间的相互作用。与通常使用HepG 2细胞进行的摄取实验相比，在此类渗透性研究期间获得的样品相对不含细胞内蛋白质或细胞碎片;因此，在分析之前不需要特殊的制备方案。在老化大蒜提取物的存在下，肝外排转运蛋白（Pgp，MRP-2）的活性发生变化，这是观察到的测试的人类免疫缺陷病毒（HIV）蛋白酶抑制剂的显著渗透性变化。达芦那韦的外排显著增加，而沙奎那韦的外排显著减少。由于观察到老化大蒜提取物和HIV蛋白酶抑制剂（地瑞那韦，沙奎那韦）之间的体外相互作用，在大蒜植物化学物质存在下，体内肝脏转运的任何改变也可能显著影响地瑞那韦/沙奎那韦肝细胞内浓度，从而影响其生物利用度。因此，这方面需要进一步的体内动物评价。
HepG2 cell monolayers, formed during cell growth on collagen-coated Transwell (R) (Corning (R) Inc., Corning, NY, USA) inserts, can be used for the evaluation of interactions between food supplements and drugs that are substrates for P-glycoprotein (Pgp) and/or multidrug resistance-associated protein 2 (MRP-2). Samples obtained during such permeability studies were relatively free of intracellular proteins or cell debris compared to usually performed uptake experiments with HepG2 cells; therefore no special preparation protocol prior to the analysis was needed. In the presence of aged garlic extract the activities of hepatic efflux transporters (Pgp, MRP-2) changed, which was observed as significant permeability changes of tested human immunodeficiency virus (HIV) protease inhibitors. Darunavir efflux significantly increased, whereas that of saquinavir significantly decreased. Because of the observed in vitro interactions between aged garlic extract and HIV protease inhibitors (darunavir, saquinavir), any alterations of in vivo liver transport in the presence of garlic phytochemicals could also significantly influence darunavir/saquinavir hepatocyte intracellular concentrations and hence their bioavailabilities. Therefore this aspect needs further in vivo animal evaluation.