The Antioxidant Effect of Erythropoietin on Thalassemic Blood Cells

Abstract

Because of its stimulating effect on RBC production, erythropoietin (Epo) is used to treat anemia, for example, in patients on dialysis or on chemotherapy. In β-thalassemia, where Epo levels are low relative to the degree of anemia, Epo treatment improves the anemia state. Since RBC and platelets of these patients are under oxidative stress, which may be involved in anemia and thromboembolic complications, we investigated Epo as an antioxidant. Using flow-cytometry technology, we found that in vitro treatment with Epo of blood cells from these patients increased their glutathione content and reduced their reactive oxygen species, membrane lipid peroxides, and external phosphatidylserine. This resulted in reduced susceptibility of RBC to undergo hemolysis and phagocytosis. Injection of Epo into heterozygous (Hbbth3/+) β-thalassemic mice reduced the oxidative markers within 3 hours. Our results suggest that, in addition to stimulating RBC and fetal hemoglobin production, Epo might alleviate symptoms of hemolytic anemias as an antioxidant.

DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress

“…Percoll-separated erythrocytes (2x10 7 /ml) were incubated with 0.4 mM 2',7'-dichlorofluorescein diacetate (DCF; Sigma-Aldrich, Germany) for 15 min at 37°C according to Amer et al [22]. For a positive control, wt erythrocytes were exposed to 2 mM H 2 O 2 for 10 min before DCF-labelling.…”

Correlation between erythropoietin serum levels and erythrocyte susceptibility to lipid peroxidation in elderly with type 2 diabetes

“…Furthermore, metabolic disturbances and oxidative stress appear to be strongly related in the etiopathogeny of type 2 diabetes. Several studies evidenced that oxidative status was improved by EPO treatment of anemia (2,11,25). EPO therapy may exert its antioxidant effect, by modulating the action of erythrocyte antioxidant enzymes such as superoxide dismutase and glutathione peroxidase (25).…”

“…EPO therapy may exert its antioxidant effect, by modulating the action of erythrocyte antioxidant enzymes such as superoxide dismutase and glutathione peroxidase (25). Also, recent results showed that EPO treatment increased the GSH levels in both erythrocytes and platelets, in β-thalassemic patients (2). However, the relationships between EPO and erythrocyte oxidative stress in elderly subjects with diabetes have been less explored.…”

“…Its ability to scavenge peroxyl (ROO˙) radicals, evaluated in vitro, was also superior compared to other antioxidants (5). The indirect antioxidant EPO action could be achieved through iron depletion and thus limitation of iron-dependent oxidative injury, and by increasing new red blood cells (RBC) loaded with a significant amount of antioxidants (1,2,11,16).…”

“…Recent in vitro and in vivo studies underline the antioxidative EPO effect in various cell systems: erythrocytes, neurons, microglia, astrocytes, cerebral endothelial cells, cardiomyocytes, retinal cell (2,11,16,20). In in vitro studies on blood vessel cells exposed to increased glucose concentrations a strong cyto-protective EPO effect was noticed (8).…”