Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants

Abstract

Summary Sickle cell disease (SCD) is basically a red blood cell (RBC) disorder characterised by sickling and haemolysis, but platelets and polymorphonuclear neutrophils (PMN) are also involved. Oxidative damage may play a role in the pathogenesis of SCD. Using flow cytometry, we measured oxidative‐state markers simultaneously in RBC, platelets and PMN obtained from 25 normal donors, nine homozygous (SS) patients and six SS/beta‐thalassaemia patients. Reactive oxygen species (ROS) and reduced glutathione (GSH) were measured following staining of blood samples with fluorescence probes and gating on specific subpopulations based on size and granularity. Ten‐ to 30‐fold higher ROS production and 20–50% lower GSH content were found in RBC, platelets and PMN from SCD patients versus those of their normal counterparts. This could in part account for the clinical manifestations, such as haemolysis, a hypercoagulable state, recurrent bacterial infections and vaso‐occlusive incidences, in SCD. We further showed that exposure of SCD samples to antioxidants, such as N‐acetyl‐cysteine, vitamin C and vitamin E, decreased their oxidative stress. These results suggest that antioxidant treatment of patients with SCD could reduce oxidative damage to RBC, PMN and platelets, thereby alleviating symptoms associated with their pathology. The flow cytometry techniques presented herein could assist in monitoring the efficacy of such treatment.

Disordered hepcidin–ferroportin signaling promotes breast cancer growth

“…The tumorigenic effect of iron has been attributed to several factors, such as overproduction of ROS and free radicals through irondependent Fenton reaction, induction of oxidative responsive transcriptional factors and pro-inflammatory cytokines and iron-mediated hypoxia signaling [39][40][41][42]. Consistent with previous studies [43,44], we demonstrated that iron treatment (FAC 32 μM, similar to the mean iron concentration in our breast cancer patients) could induce about 1.9-fold increase of intracellular ROS level in MBA-MB-231 cells compared to the control (Fig. 8A, P b 0.001), while DFO significantly reduced ROS generation (Fig.…”

Stabilization of erythrocytes against oxidative and hypotonic stress by tannins isolated from sumac leaves (Rhus typhina L.) and grape seeds (Vitis vinifera L.)

“…The oxidative stress of erythrocytes accompanies many pathological conditions, such as sickle cell and iron deficiency anemias and thalassemia [8,29,30], as well as aging [17,31], hypoxia [9] and obesity [32]. An intensive search has been going on for natural antioxidants to treat diseases induced by RONS.…”

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

“…Increased amounts of oxidizing molecules, such as ROS, are produced during periods of reperfusion (Dhalla et al, 2000;Klings & Farber, 2001) and when neutrophils become activated or adhere to the endothelium (Mohamed et al, 1993;Hofstra et al, 1996). Previous studies have shown a 10-to 30-fold higher ROS production in red bld cells, platelets and polymorphonuclear neutrophils from SCD patients, compared with their normal counterparts (Amer et al, 2006). Signals transduced by adhesion molecules play a critical role in ROS production by eosinophils (Chihara et al, 1995).…”