Suominen Laura, Stenberg Emilia, Sjöstedt Noora, Kidron Heidi
Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki FI-00014, Finland.
Mol Pharm. 2025 Sep 1;22(9):5627-5637. doi: 10.1021/acs.molpharmaceut.5c00705. Epub 2025 Aug 7.
Food additives are chemical substances that are added to processed food to improve its flavor, texture, or appearance. Food additives can inhibit intestinal transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), organic anion transporting polypeptide 2B1 (OATP2B1), and P-glycoprotein (P-gp). This inhibition could potentially affect the absorption of their substrate drugs and cause unwanted food-drug interactions. In this study, 22 food additives were evaluated for their impact on BCRP, MRP2, OATP2B1, and P-gp transport. The inhibition potency toward intestinal transporters was first studied using membrane vesicles and HEK293 cells. In these assays, four food additives (beta-carotene, butylated hydroxytoluene, dodecyl gallate, and octyl gallate) were identified as inhibitors. Seven food additives (allura red AC, beta-carotene, brilliant blue FCF, carmoisine, neohesperidin DC, sunset yellow FCF, and tartrazine), which were identified as inhibitors either in the current study or in our previous studies, were selected for Caco-2 permeability studies to further evaluate their possible effect on drug absorption. None of the selected food additives showed any effect on sulfasalazine permeability. These results suggest that the selected food additives are inhibitors of the studied transporters but are unlikely to cause clinically significant intestinal transporter-mediated drug interactions.
食品添加剂是添加到加工食品中以改善其风味、质地或外观的化学物质。食品添加剂可抑制肠道转运蛋白，如乳腺癌耐药蛋白（BCRP）、多药耐药相关蛋白2（MRP2）、有机阴离子转运多肽2B1（OATP2B1）和P-糖蛋白（P-gp）。这种抑制作用可能会影响其底物药物的吸收，并导致不良的食物-药物相互作用。在本研究中，评估了22种食品添加剂对BCRP、MRP2、OATP2B1和P-gp转运的影响。首先使用膜囊泡和HEK293细胞研究了对肠道转运蛋白的抑制效力。在这些试验中，四种食品添加剂（β-胡萝卜素、丁基羟基甲苯、十二烷基没食子酸酯和辛基没食子酸酯）被鉴定为抑制剂。七种食品添加剂（诱惑红AC、β-胡萝卜素、亮蓝FCF、胭脂红、新橙皮苷二氢查耳酮、日落黄FCF和柠檬黄），在本研究或我们之前的研究中被鉴定为抑制剂，被选用于Caco-2通透性研究，以进一步评估它们对药物吸收的可能影响。所选食品添加剂均未对柳氮磺胺吡啶的通透性产生任何影响。这些结果表明，所选食品添加剂是所研究转运蛋白的抑制剂，但不太可能引起临床上显著的肠道转运蛋白介导的药物相互作用。
