Monitoring of MRP-like activity in human erythrocytes: inhibitory effect of isoflavones.
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 (IC(50)) of BCPCF efflux at 15-70 microM. The IC(50) value of the most efficient isoflavone, licoisoflavone A (15-25 microM), was comparable to that of indomethacin (approximately 10 microM) and markedly lower than for probenecid (100-200 microM), 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.
Bobrowska-Hägerstrand
M
M
Department of Biology, Abo Akademi University, Abo/Turku, FIN-20520, Finland.
Wróbel
A
A
Rychlik
B
B
Bartosz
G
G
Söderström
T
T
Shirataki
Y
Y
Motohashi
N
N
Molnár
J
J
Michalak
K
K
Hägerstrand
H
H
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D005452:Fluoresceins / Q000493:pharmacokinetics; D005456:Fluorescent Dyes; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000494:pharmacology* / Q000633:toxicity; D007700:Kinetics
C473073:2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007529:Isoflavones; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid