Reactive Species in Sickle Cell Disease

Abstract

A BSTRACT : The red cell is a relatively abundant locus of both free radical generation and reaction. Erythrocytes have a high content of unsaturated membrane lipids, a rich oxygen supply and are densely packed with redox-active hemoglobin residues. In response, red cells have a highly evolved and well-integrated network of oxidant defense mechanisms that lend an ability to withstand oxidative stress. In the case of congenital hemoglobin mutations that underlie sickle cell disease, they become very susceptible to free radical-mediated injury by virtue of enhanced endogenous rates of production of reactive species and impairment of tissue free radical defense mechanisms. In sickle cell disease, a combination of these susceptibility factors are hypothesized to lead to an overall impairment of vascular function, in large part due to loss of "bioactive" nitric oxide via the free radical-mediated consumption of this vasoactive molecule.

Ginkgo biloba extract (EGb 761) attenuates oxidative stress induction in erythrocytes of sickle cell disease patients

“…As expected, our experiments detected greater hemoglobin oxidation and lipid peroxidation in the erythrocytes of SS patients. A majority of studies on the SCD population have reported deficits in concentration of GSH (Hebbel et al, 1982;Wetterstroem, 1984;Hebbel, 1990;Hebbel, Leung, Mohandas, 1990;Aslan, Thornley-Brown, Freeman, 2000;Reid et al, 2006;Morris et al, 2008), while others have not found this pattern (Rice-Evans, Omorphos, Baysal, 1986;Somjee et al, 2004;Manfredini et al, 2008;Nur et al, 2011). Moreover, the GSSG (oxidized glutathione)/ GSH index was significantly elevated in SCD patients, supporting an important role for oxidative damage in these cells (Morris et al, 2008;Rusanova, 2010).…”

“…In hemoglobinopathies, including sickle cell disease (SCD), red blood cells are rendered more susceptible to oxidative damage because they produce greater amounts of reactive oxygen species (Aslan, Thornley-Brown, Freeman, 2000). Moreover, in SCD red blood cells are more susceptible to oxidation (Chaves, Leonart, Nascimento, 2008) and have a reduced ability to defend against oxidation (Fasola et al, 2007).…”

Effect of Iron Supplementation on Plasma Lipid Levels in Pregnant Anemic Women

“…However, IDA, RBCs produces greater quantities of O 2˙¯, H 2 O 2 and OH˚ than do normal RBC [30]. Besides, iron deficiency anemia, RBCs exhibit increased levels of thiobarbituric acid-reactive substances, suggesting that they are targets for oxidative stress [31]. During deoxygenation of haemoglobin, there is a transfer of electrons between iron atom and O 2 leading to the production of O 2˙¯.…”

“…Within the RBC, one of the targets of oxidant damage is the plasma membrane. In the presence of O 2˙¯g enerating system, iron (III) is reduced to iron (II) with subsequent formation of OH˚ and H 2 O 2 [30][31]. The hydroxyl radical oxidizes unsaturated esterified membrane lipids, resulting in changes in fluidity of the bilayer.…”

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease

“…In one study, F eNO was reduced in SCD patients (11), a possible explanation is reduced nitric oxide (NO) bioavailability resulting from chronic hemolysis and NO scavenging by the cell free hemoglobin (12). A reduced F eNO , however, has not been found in other cohorts (13,14).…”