Nonspecific serum iron in thalassemia: Quantitation and chemical reactivity

Abstract

We reported earlier an abnormal iron population in the serum of patients with transfusional hemosiderosis secondary to thalassemia. The iron is not bound to transferrin, ferritin, or hemoglobin and is referred to as nonspecific iron. This publication reports studies of the chemical reactivity and nature of the nonspecific iron and the development and validation of a method for its quantitative analysis. The quantitation depends on the mobilization of this iron from nonspecific macromolecular binding sites by ethylenediamine tetraacetic acid and subsequent separation from Fe3+-transferrin-C0: -and residual hemogIobin by ultrafiltration. Analyses of filtrate iron were carried out by atomic absorption and colorimetric methods. The accuracy of the test was established via an ultrafiltration titration of serum of known unsaturated iron-binding capacity, The method proved to be accurate and highly reproducible. Sera containing artificial introduced nonspecific iron were prepared. The reactivity of artificial and thalassemic nonspecific iron was examined with regard to reduction and chelation, and chelation by apotransferrin. Artificial and thalassemic nonspecific iron were found to be virtually identical in reactivity and t o exhibit multiphasic kinetics consistent with nonspecific binding to several serum protein sites. The reaction of apotransferrin with nonspecific iron was complete within one minute. The reduction-chelation and apotransferrin reactivity studies offer independent analyses of nonspecific serum iron concentrations which compared closely with the chelation-ultrafiltration technique.

Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complications

“…Iron in its free form i.e., in non-transferrin bound form is known to induce oxidation of biomolecules through Heber-Weiss and Fenton reactions by producing harmful hydroxyl radicals (4). This nontransferrin bound iron or free iron has been found in various disease conditions like hemochromatosis (5), thalasemias (6) and patients on supplemental iron therapy (7). In our previous work we also found such free iron in hemodialysis patients not on any supplemental iron (8).…”

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.…”

Nature of nontransferrin‐bound iron

“…The chemistry of the assay is extremely complex and is critically dependent on the source of bleomycin [4] (Fig. 3, formula 4).…”