Non‐Specific Serum Iron in Thalassaemia: an Abnormal Serum Iron Fraction of Potential Toxicity

Abstract

Iron binding in the sera of 35 patients with beta thalassaemia major and intermedia was studied. In patients receiving regular blood transfusions since infancy transferrin was completely saturated and about 2.7--7.1 mumol/l of the serum iron could be removed by dialysis or ultrafiltration in the presence of a chelating agent or by filtration on DEAE-Sephadex-catecholdisulphonic acid columns. In contrast, less than 1.0 mumol/l of transferrin bound iron was removed when subjected to the same procedures. The non-specific iron of thalassaemic sera could no longer be demonstrated after incubation with normal serum. These findings indicate that non-specific iron is a chelatable with normal serum. These findings indicate that non-specific iron is a chelatable compound which is readily available for transferrin binding. In view of the known toxicity of unbound iron, its identification in thalassaemic sera might be of relevance to the pathogenesis of tissue damage and the protective effect of iron chelating therapy in this disease.

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

“…This is the reason why levels of NTBI in normal healthy individual do not exceed 1 lmol/L, and often undetectable by most of the methods [13]. In the iron overload scenarios like thalassemia; hemochromatosis and others iron gets a chance to exist in form which is not bond to Tf [2,[14][15][16][17][18]. Increased levels of NTBI in the above mentioned situations is easily explainable whereas it is difficult to give a convenient explanation for the raised levels of NTBI where Tf saturation is not high [18][19][20].…”

“…Endogenous source is more important factor as iron absorption is well regulated at the mucosal level. In hemolytic anemia, increased endogenous inflow of iron due to excess haemolysis and/or compensatory blood transfusion may cause higher saturation of Tf leading to existence of NTBI [2,14,15,21]. Lee et al [22] reported the existence of NTBI in diabetes mellitus.…”

“…There is a lacunae in the literature regarding the precise way of removal and the shelf life of NTBI, though some studies state its clearance from highly vascular organs like liver and heart [1]. Even after lapse of 34 years of its first mentioning of NTBI by Hershko et al [2] the equivocal of definition of NTBI is difficult proposition due its heterogeneous nature.…”

Non‐transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

“…This led to simple and sensitive assays that are performed under nearly physiological conditions, with 40-lM ascorbate added to initiate redox cycling of the iron and ensuing generation of reactive oxygen species (ROS) that are quantified by a fluorescence assay (Table I). Furthermore, unlike other studies [11,14,15], the LPI assay does not depend on supplementation of strong iron-mobilizing agents, or high-affinity chelators [16,20]. Thus, the assay avoids the inadvertent detection of TBI [15] or labile iron-chelates [19,[21][22][23].…”

Iron status and oxidative stress in β‐thalassemia patients in Jakarta

“…Transition metals such as iron, and some iron-containing low molecular weight compounds play an important role in the generation of reactive oxygen species (ROS) and free radicals, which are supposed to damage cellular and subcellular structures and cause metabolic dysfunction [3,4,9,10,12,19]. Inter alia, the disturbed iron metabolism generates oxygen-derived free radicals in thalassemias.…”