Monitoring of MRP-like activity in human erythrocytes:: Inhibitory effect of isoflavones

被引:35
作者
Bobrowska-Hagerstrand, M
Wróbel, A
Rychlik, B
Bartosz, G
Söderström, T
Shirataki, Y
Motohashi, N
Molnár, J
Michalak, K
Hägerstrand, H [1 ]
机构
[1] Abo Akad Univ, Dept Biol, FIN-20520 Turku, Finland
[2] Wroclaw Univ Technol, Inst Phys, PL-50370 Wroclaw, Poland
[3] Univ Lodz, Dept Mol Biophys, PL-90237 Lodz, Poland
[4] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku, Finland
[5] Abo Akad Univ, Turku Ctr Biotechnol, FIN-20520 Turku, Finland
[6] Josai Univ, Fac Pharmaceut Sci, Sakado, Saitama 3500295, Japan
[7] Meiji Pharmaceut Univ, Tokyo 2048588, Japan
[8] Albert Szent Gyorgyi Med Univ, Dept Microbiol, H-6720 Szeged, Hungary
[9] Wroclaw Med Univ, PL-50368 Wroclaw, Poland
关键词
multidrug resistance; erythrocyte; BCPCF; isoflavonoid; indomethacin; probenecid; DIDS;
D O I
10.1006/bcmd.2001.0459
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A method to fluorometrically monitor efflux of 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was developed. Genistein, daidzein, sophoraisoflavone A, and licoisoflavone A induced 50% inhibition (IC50) of BCPCF efflux at 15-70 muM. The IC50 value of the most efficient isoflavone, licoisoflavone A (15-25 muM), was comparable to that of indomethacin (similar to 10 muM) and markedly lower than for probenecid (100-200 muM), both known MRP1 inhibitors. Our results indicate that the human erythrocyte is a useful cell model in screening potential MRP inhibitors, that BCPCF is a good substrate for MRP, and that some isoflavones at low concentrations inhibit MRP-mediated efflux. (C) 2001 Academic Press.
引用
收藏
页码:894 / 900
页数:7
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