TY - JOUR
T1 - Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease
T2 - A comprehensive review
AU - Pavitra, Eluri
AU - Acharya, Rakesh Kumar
AU - Gupta, Vivek Kumar
AU - Verma, Henu Kumar
AU - Kang, Haneul
AU - Lee, Jeong Hwan
AU - Sahu, Tarun
AU - Bhaskar, L. V.K.S.
AU - Raju, Ganji Seeta Rama
AU - Huh, Yun Suk
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Hemolysis
KW - Oxidative stress
KW - Reactive oxygen species
KW - Red blood cells
KW - Sickle cell disease
UR - http://www.scopus.com/inward/record.url?scp=85194915591&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2024.116849
DO - 10.1016/j.biopha.2024.116849
M3 - Review article
C2 - 38823275
AN - SCOPUS:85194915591
SN - 0753-3322
VL - 176
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 116849
ER -