title: Modulation of multidrug resistance-associated proteins function in erythrocytes in glycerol-induced acute renal failure rats.
abstract: OBJECTIVE
  Evaluation of the function of multidrug resistance-associated proteins (MRPs) expressed in erythrocytes and screening of endogenous MRPs modulator(s) in glycerol-induced acute renal failure (ARF) rats.
  
  
  METHODS
  Concentrations of 2,4-dinitrophenyl-S-glutathione (DNP-SG), a substrate for MRPs, in erythrocytes after administration of 1-chloro-2,4-dintrobenzene (CDNB), a precursor of DNP-SG, were determined in control and ARF rats. The screening of endogenous MRPs modulator(s) was performed using washed erythrocytes and inside-out erythrocyte membrane vesicles (IOVs) in vitro.
  
  
  RESULTS
  Accumulation of DNP-SG in erythrocytes was observed in ARF rats. Uraemic plasma components exhibited a greater inhibitory effect on DNP-SG uptake by IOVs than control plasma components and increased the DNP-SG accumulation significantly in washed erythrocytes. Several protein-bound uraemic toxins at clinically observed concentrations and bilirubin significantly inhibited DNP-SG uptake by IOVs. In washed erythrocytes, bilirubin (10 μm) and l-kynurenine (100 μm), a precursor of kynurenic acid being MRPs inhibitor, increased DNP-SG accumulation significantly.
  
  
  CONCLUSIONS
  Glycerol-induced ARF rats contain various MRPs inhibitors in plasma, and membrane-permeable MRP substrates/inhibitors including their precursors inhibit the MRPs function in erythrocytes cooperatively.
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Matsushima
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oda
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Mori
authors.affiliation: Laboratory of Biopharmaceutics and Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Murakami
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects*; D004137:Dinitrochlorobenzene / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood; D005990:Glycerol; D007737:Kynurenine / Q000494:pharmacology; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D001663:Bilirubin; D004137:Dinitrochlorobenzene; D005978:Glutathione; D005990:Glycerol; D007737:Kynurenine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C030190:S-(2,4-dinitrophenyl)glutathione
keywords: acute renal failure; erythrocytes; inside-out erythrocyte membrane vesicles; multidrug resistance-associated proteins; uraemic toxin