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

Blood Cells Mol Dis. 2001 Sep-Oct;27(5):894-900. doi: 10.1006/bcmd.2001.0459.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Dose-Response Relationship, Drug
  • Erythrocytes / metabolism*
  • Fluoresceins / pharmacokinetics
  • Fluorescent Dyes
  • Hemolysis / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Isoflavones / pharmacology*
  • Isoflavones / toxicity
  • Kinetics

Substances

  • 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Fluoresceins
  • Fluorescent Dyes
  • Isoflavones
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid