The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia

Oxidative damage to red blood cells (RBCs) may contribute to pathogenesis of sickle cell anemia. 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 hypothesize that antioxidant...

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Main Authors: Halima Al Balushi, Anke Hannemann, David Rees, John Brewin, John Stanley Gibson
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2019.00976/full
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author Halima Al Balushi
Anke Hannemann
David Rees
John Brewin
John Stanley Gibson
author_facet Halima Al Balushi
Anke Hannemann
David Rees
John Brewin
John Stanley Gibson
author_sort Halima Al Balushi
collection DOAJ
description Oxidative damage to red blood cells (RBCs) may contribute to pathogenesis of sickle cell anemia. 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 hypothesize that antioxidants may also have beneficial effects on the abnormal membrane permeability of sickle cells. Increased cation permeability of these cells encourages HbS polymerization by causing RBC dehydration and also leads to externalization 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 hemolysis. 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.
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spelling doaj.art-4dbec1d684f04d5b9bcb2eb209b2b8e02022-12-21T23:20:08ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-08-011010.3389/fphys.2019.00976469675The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell AnemiaHalima Al Balushi0Anke Hannemann1David Rees2John Brewin3John Stanley Gibson4Department of Veterinary Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United KingdomDepartment of Paediatric Haematology, King’s College Hospital, King’s College London, London, United KingdomDepartment of Paediatric Haematology, King’s College Hospital, King’s College London, London, United KingdomDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United KingdomOxidative damage to red blood cells (RBCs) may contribute to pathogenesis of sickle cell anemia. 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 hypothesize that antioxidants may also have beneficial effects on the abnormal membrane permeability of sickle cells. Increased cation permeability of these cells encourages HbS polymerization by causing RBC dehydration and also leads to externalization 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 hemolysis. 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.https://www.frontiersin.org/article/10.3389/fphys.2019.00976/fullantioxidantsickle celldithiothreitolN-acetylcysteinequercetinK+ permeability
spellingShingle Halima Al Balushi
Anke Hannemann
David Rees
John Brewin
John Stanley Gibson
The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
Frontiers in Physiology
antioxidant
sickle cell
dithiothreitol
N-acetylcysteine
quercetin
K+ permeability
title The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
title_full The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
title_fullStr The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
title_full_unstemmed The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
title_short The Effect of Antioxidants on the Properties of Red Blood Cells From Patients With Sickle Cell Anemia
title_sort effect of antioxidants on the properties of red blood cells from patients with sickle cell anemia
topic antioxidant
sickle cell
dithiothreitol
N-acetylcysteine
quercetin
K+ permeability
url https://www.frontiersin.org/article/10.3389/fphys.2019.00976/full
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