Iron release in erythrocytes from patients withβ-thalassemia

Abstract

Our previous studies have shown that iron is released in a free (desferrioxamine-chelatable) form when erythrocytes undergo oxidative stress (incubation with oxidizing agents or aerobic incubation in buffer for 24-60 h (a model of rapid in vitro ageing)). The release is accompanied by oxidative alterations of membrane proteins as well as by the appearance of senescent antigen, a signal for termination of old erythrocytes. In hemolytic anemias by hereditary hemoglobin alterations an accelerated removal of erythrocytes occurs. An increased susceptibility to oxidative damage has been reported in beta-thalassemic erythrocytes. Therefore we have investigated whether an increased iron level and an increased susceptibility to iron release could be observed in the erythrocytes from patients with beta-thalassemia. Erythrocytes from subjects with thalassemia intermedia showed an extremely higher content (0 time value) of free iron and methemoglobin as compared to controls. An increase, although non-statistically-significant, was seen in erythrocytes from subjects with thalassemia major. Upon aerobic incubation for 24 h the release of iron in beta-thalassemic erythrocytes was by far greater than in controls, with the exception of thalassemia minor. When the individual values for free iron content (0 time) seen in thalassemia major and intermedia were plotted against the corresponding values for HbF, a positive correlation (P < 0.001) was observed. Also, a positive correlation (P < 0.01) was seen between the values for free iron release (24 h incubation) and the values for HbF. These results suggest that the presence of HbF is a condition favourable to iron release. Since in beta-thalassemia the persistance of HbF is related to the lack or deficiency of beta chains and therefore to the excess of alpha chains, the observed correlation between free iron and HbF, is consistent with the hypothesis by others that excess of alpha chains represents a prooxidant factor.

Free Radicals, Oxidative Stress and Antioxidants

“…In thalassemic erythrocytes, besides the release (24 h incubation), the content of free iron (at 0 time) is also increased (Fig.21A). Both values are correlated with HbF content (30). In the erythrocytes from newborns (31) the release is increased in both term and preterm newborns (Fig.21B) and it is correlated (31) with the levels of plasma non proteinbound iron (NPBI), a form of non bound iron of uncertain origin, which appears in plasma of newborns, thalassemic and hemochromatotic patients.…”

“…An increased release of iron after aerobic incubation is also observed (30) in erythrocytes from subjects with β-thalassemia (major and intermedia) (Fig.21) and in erythrocytes from neonates (31). In both cases an increased susceptibility to oxidative stress, an accelerated removal from the blood stream and a marked increase of hemoglobin F (HbF) occurs.…”

Red Blood Cell Involvement in Fetal/Neonatal Hypoxia

“…Release is accompanied by the oxidation of membrane proteins and the appearance of senescent antigen, as measured by autologous IgG binding [40]. Increased ICRBC has been reported in various red cell abnormalities, including sickle cell anemia and thalassemia [41,42]. Free radical release in these red cells is complex and does not necessarily involve xenobiotics or other exogenous oxidative stress [41].…”

Combination of two rare mutations causes β-thalassaemia in a Bangladeshi patient

“…The imbalance in the α-chain: β-chain ratio and the instability of the β-chain in β-thalassaemia result in the increase of serum-free haem (Ciccoli et al , 1999; Koren et al , 2008). Free haem results in increased generation of reactive oxygen species (Ciccoli et al , 2003; Amer and Fibach, 2004), which in turn results in increased Egr1 expression via MAPK ERK-1/2, Elk-1 and NF-κB (Hasan and Schafer, 2008).…”