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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Format: | Article |
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Frontiers Media S.A.
2019-08-01
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Series: | Frontiers in Physiology |
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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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issn | 1664-042X |
language | English |
last_indexed | 2024-12-14T02:36:13Z |
publishDate | 2019-08-01 |
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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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