title: Monitoring of MRP-like activity in human erythrocytes: inhibitory effect of isoflavones.
abstract: 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.
authors.affiliation: Department of Biology, Abo Akademi University, Abo/Turku, FIN-20520, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Bobrowska-Hägerstrand
authors.forename: A
authors.initials: A
authors.lastname: Wróbel
authors.forename: B
authors.initials: B
authors.lastname: Rychlik
authors.forename: G
authors.initials: G
authors.lastname: Bartosz
authors.forename: T
authors.initials: T
authors.lastname: Söderström
authors.forename: Y
authors.initials: Y
authors.lastname: Shirataki
authors.forename: N
authors.initials: N
authors.lastname: Motohashi
authors.forename: J
authors.initials: J
authors.lastname: Molnár
authors.forename: K
authors.initials: K
authors.lastname: Michalak
authors.forename: H
authors.initials: H
authors.lastname: Hägerstrand
mesh_terms: 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
chemical_list: 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