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  • Title: Effectiveness of oral iron chelators assayed in the rat.
    Author: Kim BK, Huebers HA, Finch CA.
    Journal: Am J Hematol; 1987 Mar; 24(3):277-84. PubMed ID: 3826055.
    Abstract:
    A 4-hour in vivo test for iron chelator activity in the rat is described. The amount of radioiron in the gut and urine that results from chelator-induced excretion of previously injected radioiron labelled ferritin is measured. Hepatocyte localization and desferrioxamine-induced radioiron mobilization from in vitro tagged homologous ferritin is shown to be similar to that from in vivo tagged ferritin. Non-homologous ferritin preparations labelled in vitro proved unsatisfactory. Radioiron mobilization by chelator occurred regardless of the iron status of the animal. Employing this measurement, the effectiveness of three iron chelators, pyridoxal isonicotinoyl hydrazone, the dimethyl ester of ethylene diamine-N, N'-dis (3-hydroxyphenyl acetic acid), and the dimethyl ester N, N'-di (3-hydroxybenzyl) ethylene-1, ethylene-1, 2-diamine-N, N'-diacetic acid, given orally was determined. All three chelators, when given in comparable dosage, induced iron excretion similar in amount to that observed with parenteral desferrioxamine. In addition, pyridoxal isonicotinoyl hydrazone administered in the diet over a period of 4 weeks was shown to reduce hepatic and splenic iron of normal animals by about one third, providing further validation of this method of evaluating chelator effectiveness.
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