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Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes.
Toxins (Basel). 2019 07 01; 11(7)T

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 (pCS) 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 < pCS < 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 pCS (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.

Authors+Show Affiliations

Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium.Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium.Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium.Department of Pharmaceutical Sciences, Pharmacology, Utrecht University, 3584 CG Utrecht, The Netherlands.Otto Loewi Research Center, Physiology, Medical University of Graz, 8010 Graz, Austria.Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium. sunny.eloot@ugent.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31266243

Citation

Deltombe, Olivier, et al. "Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes." Toxins, vol. 11, no. 7, 2019.
Deltombe O, Glorieux G, Marzouki S, et al. Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins (Basel). 2019;11(7).
Deltombe, O., Glorieux, G., Marzouki, S., Masereeuw, R., Schneditz, D., & Eloot, S. (2019). Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins, 11(7). https://doi.org/10.3390/toxins11070385
Deltombe O, et al. Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins (Basel). 2019 07 1;11(7) PubMed PMID: 31266243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. AU - Deltombe,Olivier, AU - Glorieux,Griet, AU - Marzouki,Sami, AU - Masereeuw,Rosalinde, AU - Schneditz,Daniel, AU - Eloot,Sunny, Y1 - 2019/07/01/ PY - 2019/05/05/received PY - 2019/06/13/revised PY - 2019/06/27/accepted PY - 2019/7/4/entrez PY - 2019/7/4/pubmed PY - 2020/8/29/medline KW - DIDS KW - KO143 KW - MK571 KW - chronic kidney disease KW - erythrocyte KW - hemodialysis KW - hippuric acid KW - indole-3-acetic acid KW - indoxyl sulfate KW - p-cresyl sulfate KW - protein-bound uremic toxins JF - Toxins JO - Toxins (Basel) VL - 11 IS - 7 N2 - 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 (pCS) 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 < pCS < 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 pCS (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. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/31266243/Selective_Transport_of_Protein_Bound_Uremic_Toxins_in_Erythrocytes_ L2 - https://www.mdpi.com/resolver?pii=toxins11070385 DB - PRIME DP - Unbound Medicine ER -