Oxidative stress in sickle cell disease: An overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies

Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O₂ ⁻) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustainin...

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Bibliographic Details
Published in:Free radical biology & medicine 2013-12, Vol.65, p.1101-1109
Main Authors: Silva, Danilo Grunig Humberto, Belini Junior, Edis, de Almeida, Eduardo Alves, Bonini-Domingos, Claudia Regina
Format: Article
Language:English
Subjects:
Anemia, Sickle Cell - drug therapy
Anemia, Sickle Cell - physiopathology
antioxidants
Antioxidants - therapeutic use
beta-Globins - genetics
Cell Adhesion
erythrocytes
Erythrocytes - metabolism
hemoglobin
Hemoglobin, Sickle - metabolism
Hemolysis
Humans
metabolism
Oxidation-Reduction
Oxidative Stress
polymerization
Reactive Oxygen Species - blood
Reperfusion Injury - complications
sickle cell anemia
superoxide anion
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Summary:Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O₂ ⁻) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body. Sickle hemoglobin molecules suffer repeated polymerization/depolymerization generating greater amounts of reactive oxygen species, which can lead to a cyclic cascade characterized by blood cell adhesion, hemolysis, vaso-occlusion, and ischemia–reperfusion injury. In other words, sickle cell disease is intimately linked to a pathophysiologic condition of multiple sources of pro-oxidant processes with consequent chronic and systemic oxidative stress. For this reason, newer therapeutic agents that can target oxidative stress may constitute a valuable means for preventing or delaying the development of organ complications.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2013.08.181