Oxidative Stress and Hematopoietic Stem Cell Dysfunction in Sickle Cell Anemia.

Abstract

Sickle Cell Anemia (SCA) is a genetic blood disorder characterized by the production of abnormal hemoglobin S, leading to red blood cell sickling and a range of severe health complications. Recent research highlights the significant role of oxidative stress in the pathophysiology of SCA, particularly its impact on hematopoietic stem cells (HSCs). Oxidative stress in SCA originates from both intrinsic factors, such as the sickling process, and extrinsic sources, including chronic inflammation and hypoxia. This review explores how reactive oxygen species (ROS) generated by these factors contribute to HSC dysfunction, impairing hematopoiesis and exacerbating disease progression. The review delves into the mechanisms by which oxidative stress affects HSCs, focusing on the generation of ROS and their effects on HSC viability, differentiation, and self-renewal. We examine how oxidative damage to DNA, lipids, and proteins disrupts HSC function and contributes to the progression of SCA. Additionally, the review highlights the impact of phospholipid oxidation on HSCs, discussing how oxidative damage leads to alterations in HSC function and contributes to disease severity. Emerging therapeutic strategies aimed at reducing oxidative stress offer hope for improving SCA management.