SICKLE CELL OXIDATIVE STRESS LASUTH CLINICAL STUDIES 2022
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SCD is a multifactorial disease in which the sickle RBC is the root cause of the disease pathogenesis. Oxidative stress in sickle RBCs due to NOX enzyme activation, along with hemoglobin autoxidation, plays an essential role in SCD pathophysiology. The production of ROS in sickle cells promotes cell adhesion, vaso-occlusion, endothelial dysfunction, hemolysis, vascular inflammation, activation of the coagulation cascade and the complement system, and organ injury. These pathological changes lead to the production of more ROS, further exacerbating the disease. Using antioxidant reagents that specifically target oxidant production in sickle RBCs could reduce the detrimental effects of oxidative stress in SCD. The recent discoveries in developing novel drugs have led to improved survival and decreased morbidity in patients with SCD, but an improved understanding of oxidative stress and its regulation, especially in sickle RBCs, could lead to targeted therapies that should improve outcomes for this patient population. Mn porphyrins, for instance, which can reduce oxidative stress in sickle RBCs as well as in leukocytes and in the endothelium, have shown, in general, remarkable therapeutic effects in the SCD mouse model. The potential therapeutic effect of Mn porphyrins to prevent the development of organ complications deserves future investigation.
