Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management

Abstract

the CURAMA Study GroupSickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management. Am. J. Hematol. 86:484-489, 2011. V

Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease

“…Moreover, NADPH oxidase activity may deplete the cellular pool of NADPH, thus impairing the ability of the RBC to maintain its antioxidant defenses. 2,13 In addition to inducing endogenous damage, erythrocyte-derived ROS, which can exit the cell via the membrane anion channel, 25 may also contribute to systemic oxidative stress by modifying the activity of plasma proteins, WBC, platelets, and endothelial cells. 1 The potential utility of antioxidant therapy in SCD is intriguing but with limited evidence to date that it can ameliorate the acute or chronic pathophysiology of the disease.…”

“…Chronic inflammation has emerged as an important pathogenic mechanism in SCD, and oxidative stress is increasingly recognized as a component of this chronic inflammatory state, inducing damage to a variety of subcellular and tissue structures. 1,2 Patients with SCD have decreased plasma levels of glutathione, vitamin C, and vitamin E, presumably due to consumption by increased oxidant production. [3][4][5] RBC and other cell types show evidence of lipid peroxidation and oxidative damage to structural proteins.…”

DNP induced oxidative stress on blood components ameliorated by Pyrrole derivative of Tinospora cordifolia.

“…This reaction occurs to a lesser extent in normal RBC. But during stress, much more O -2 is generated leading to denaturation, precipitation, haemichrome formation and ROS production [36,37]. Aqueous extract of T. cordifolia inhibited fenton reaction in a dose dependent fashion with an IC50 value of 700 mg/ml [38].…”

Studies of the Anti Oxidant Status in Subjects With Altered Metabolism in Niger Delta Region of Nigeria

“…It is the most common genetic disorder in persons of African Origin (Huisman, 1981) and its associated with several complications, including oxidative stress and generation of free radicals (Yoshikawa et al, 2000).There has been a growing body of evidence suggesting that an increase in oxidative stress and abnormal oxidants/antioxidants balance are implicated in the pathophysiology of several dysfunction observed in sickle cell anaemia (Nur et al, 2011) resulting in various haematological and biochemical changes (Odievre et al, 2011), that includes production of reactive oxygen species (ROS) like superoxide radicals, hydrogen peroxide, hydroxyl radicals and nitric oxide.…”

“…Antioxidants terminate these chain reactions by removing free radical intermediate and inhibit the oxidation reactions (West, 2000). Oxidative stress, as has been hypothesized is a key player in the pathogenesis of several diseases that includes hypertension (Rodrigo et al, 2011), diabetes mellitus (Beynes and Thorpe, 1996) and sickle cell anaemia (Nur et al, 2011).…”