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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.00976

The effect of antioxidants on the properties of red blood cells from patients with sickle cell anaemia

Halima Al Balushi1, Anke Hannemann1,  David Rees2, John Brewin2 and  John S. Gibson1*
  • 1University of Cambridge, United Kingdom
  • 2King's College London, United Kingdom

Oxidative damage to red blood cells (RBCs) may contribute to pathogenesis of sickle cell anaemia. Reducing the deleterious effects of oxidants by exposing RBCs to a number of antioxidants has been shown to have protective effects against lipid and protein peroxidation. We hypothesise that antioxidants may also have beneficial effects on the abnormal membrane permeability of sickle cells. Increased cation permeability of these cells encourages HbS polymerisation by causing RBC dehydration and also leads to externalisation of the prothrombotic aminophospholipid phosphatidylserine (PS). Three antioxidants with different mechanisms of action were investigated – dithiothreitol, N-acetylcysteine and quercetin. All three were found to inhibit the main cation pathways responsible for dehydration – the deoxygenation-induced cation conductance (or Psickle), the Ca2+-activated K+ channel (or Gardos channel) and the K+-Cl- cotransporter. They also reduced Ca2+-induced PS exposure and haemolysis. Findings provide evidence for additional beneficial actions of antioxidants in maintenance of rheology and reducing vascular adhesion, and further inform the rationale for their clinical use.

Keywords: antioxidant, Permeability, Sickle cell anaemia, Quercetin, N-acetylcysteine, Dithiothreitol, Sickling, haemolysis

Received: 02 May 2019; Accepted: 11 Jul 2019.

Edited by:

Gregory Barshtein, Hebrew University of Jerusalem, Israel

Reviewed by:

Patrick G. Gallagher, Yale University, United States
Tamas Alexy, University of Minnesota Twin Cities, United States  

Copyright: © 2019 Al Balushi, Hannemann, Rees, Brewin and Gibson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. John S. Gibson, University of Cambridge, Cambridge, United Kingdom,