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Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes

Authors
  • Deltombe, Olivier1
  • Glorieux, Griet1
  • Marzouki, Sami1
  • Masereeuw, Rosalinde2
  • Schneditz, Daniel3
  • Eloot, Sunny1
  • 1 Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium
  • 2 Department of Pharmaceutical Sciences, Pharmacology, Utrecht University, 3584 CG Utrecht, The Netherlands
  • 3 Otto Loewi Research Center, Physiology, Medical University of Graz, 8010 Graz, Austria
Type
Published Article
Journal
Toxins
Publisher
MDPI AG
Publication Date
Jul 01, 2019
Volume
11
Issue
7
Identifiers
DOI: 10.3390/toxins11070385
PMID: 31266243
PMCID: PMC6669440
Source
PubMed Central
Keywords
License
Green

Abstract

To better understand the kinetics of protein-bound uremic toxins (PBUTs) during hemodialysis (HD), we investigated the distribution of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p -cresyl sulfate ( p CS) in erythrocytes of HD patients. Their transport across the erythrocyte membrane was explored in the absence of plasma proteins in vitro in a series of loading and unloading experiments of erythrocytes from healthy subjects and HD patients, respectively. Furthermore, the impact of three inhibitors of active transport proteins in erythrocytes was studied. The four PBUTs accumulated in erythrocytes from HD patients. From loading and unloading experiments, it was found that (i) the rate of transport was dependent on the studied PBUT and increased in the following sequence: HA < IS < p CS < IAA and (ii) the solute partition of intra- to extra-cellular concentrations was uneven at equilibrium. Finally, inhibiting especially Band 3 proteins affected the transport of HA (both in loading and unloading), and of IS and p CS (loading). By exploring erythrocyte transmembrane transport of PBUTs, their kinetics can be better understood, and new strategies to improve their dialytic removal can be developed.

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