Synthetic Chelating Agents in Iron Metabolism*

Cleton, F. J.; Turnbull, Adam; Finch, Clement A.

doi:10.1172/jci104719

Cited by 52 publications

(12 citation statements)

References 18 publications

(15 reference statements)

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“…Unlike transferrin-bound iron, free iron is highly toxic. DTPA is unable to penetrate cells and several studies in animals indicate that the source of iron chelated by this drug is extracellular (Cleton et al, 1963;Hershko, 1975). In accidental oral iron overdose, absorbed iron exceeds the latent iron binding capacity of transferrin and large amounts of unbound iron are deposited in tissues resulting in hepatic necrosis, metabolic acidosis and cardiovascular collapse (Fischer, 1967;Westlin, 1966).…”

Section: Discussionmentioning

confidence: 99%

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

Hershko¹,

Graham²,

Bates³

et al. 1978

Br J Haematol

404

200

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hershko¹,

Graham²,

Bates³

et al. 1978

Br J Haematol

404

200

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“…5), the re-240 360 gression slope indicating that for a change in one there was a proportionally identical change in (Foreman, Vier, and Magee, 1953;nHELATABLE IRON IN CONTROL SUB-Foreman and Trujillo, 1954;Foreman, 1960;AND PATIENTS WITH HAEMOCHRO-Stevens et al, 1962;Cleton et al, 1963). After is intravenous injection these compounds disappear sults are summarized in Table I.…”

Section: Endogenous Iron Excretion Produced By Dtpa In Control Subjecmentioning

confidence: 97%

“…stores, reflecting an effect of the latter on the stability of the iron-chelate complex in vivo. Cleton et al (1963) showed that in the rabbit the retained iron became widely distributed in the tissues, and that in both the rabbit and in man it was partly used for haemoglobin synthesis in a quantitatively similar manner to transferrin iron.…”

Section: Dtpa-chelatable Iron and Mobilizablementioning

confidence: 99%

“…Clinical studies have suggested that iron excretion after DTPA closely reflects the size of the stores (Walsh, Perkins, Blackburn, Sanford, and Cantrill, 1963;Powell and Thomas, 1967). However, there is evidence that the iron-DTPA complex dissociates to a considerable and variable extent in vivo (Cleton, Turnbull, and Finch, 1963); as only the iron of the undissociated complex can be excreted, it follows that the iron present in the urine may not be a constant sample of the quantity chelated in the tissues.…”

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confidence: 99%

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Quantitative measurement of iron stores with diethylenetriamine penta-acetic acid

Barry¹,

Cartei²,

Sherlock³

1970

Gut

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SUMMARY The use of the chelating agent diethylenetriamine penta-acetic acid (DTPA) for measuring body storage iron was investigated in patients with iron excess whose stores could be determined by venesection.Iron excretion after DTPA bore a close semi-logarithmic relationship to body iron stores when these were increased. The excretion of DTPA-bound 59Fe was similarly related to the size of the stores, indicating that the increased iron excretion produced by DTPA in iron overload states reflects both increased tissue iron available for chelation and greater stability of the iron-chelate complex. Evidence was obtained that injected 59Fe-DTPA could be used as a marker for chelated tissue iron enabling the DTPA-chelatable body iron pool to be calculated.There was a highly significant correlation between DTPA-chelatable iron and body storage iron. The regression intercept approximated to the origin, implying a specific relation between the DTPA effect and storage iron. The SE of the mean estimate for storage iron on DTPAchelatable iron was 0.25 g (5.6 %).Mean storage iron values of 392 mg for males and 243 mg for females were predicted from the findings in control subjects.

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“…following intravenous injection appears to be relatively simple. It is distributed widely in the extracellular compartment; 80 to 90 % ofthe administered dose is recovered unchanged in the urine in the first four hours; it does not participate in normal iron exchange between effete red cells, reticuloendothelial cells, and transferrin; and it appears that only tissue iron is chelated (Stevens, Rosoff, Weiner, and Spencer, 1962;Cleton, Turnbull, and Finch, 1963). These properties suggest that D.T.P.A.…”

mentioning

confidence: 99%

Use of diethylenetriamine penta-acetic acid (D.T.P.A.) in the clinical assessment of total body iron stores

Powell

Thomas

1967

Journal of Clinical Pathology

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Synthetic Chelating Agents in Iron Metabolism*

Cited by 52 publications

References 18 publications

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

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

Quantitative measurement of iron stores with diethylenetriamine penta-acetic acid

Use of diethylenetriamine penta-acetic acid (D.T.P.A.) in the clinical assessment of total body iron stores

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