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Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease: A comprehensive review.
BIOMED. PHARMACOTHER. 176:116849 (2024)
Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.
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Publication type
Article: Journal article
Document type
Review
Keywords
Antioxidants ; Hemolysis ; Oxidative Stress ; Reactive Oxygen Species ; Red Blood Cells ; Sickle Cell Disease; Nitric-oxide; Clinical-manifestations; Genetic Polymorphisms; Reperfusion Injury; Controlled-trial; Hemoglobin; Hemolysis; Pathophysiology; Anemia; Dysfunction
ISSN (print) / ISBN
1950-6007
e-ISSN
0753-3322
Journal
Biomedicine & pharmacotherapy
Quellenangaben
Volume: 176,
Article Number: 116849
Publisher
Elsevier
Publishing Place
Paris
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
Grants
Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education