Iron mobilization from myocardial cells by 3-hydroxypyridin-4-one chelators: studies in rat heart cells in culture

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Iron mobilization from myocardial cells by 3-hydroxypyridin-4-one chelators: studies in rat heart cells in culture.

The ability of 3-hydroxypyridin-4-ones (CP), a family of bidentate orally effective iron chelators, to remove iron and to prevent iron-induced lipid peroxidation was studied in beating rat myocardial cells in culture. The iron (III) binding constant (log beta 3) of all CP compounds is 36, but their lipophilicity may be modified by altering the length of the R2 substituent on the ring nitrogen. ...

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Origin and fate of iron mobilized by the 3-hydroxypyridin-4-one oral chelators: studies in hypertransfused rats by selective radioiron probes of reticuloendothelial and hepatocellular iron stores.

The mechanism of in vivo iron chelation by 3-hydroxypyridin-4-ones (CP compounds) was studied in hypertransfused rats in which the major storage iron pools in hepatocytes and in the reticuloendothelial (RE) system have been labeled by selective radioiron probes. Both dimethyl-3-hydroxypyridin-4-one (CP 20 or L1) and diethyl-3-hydroxypyridine-4-one (CP 94) have an identical and very high (log be...

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3-Hydroxypyridin-4-one Iron Chelators in Leukemia Cell Lines Cell Cycle Synchronization and Growth Inhibition by Updated Version

The effect of bidentate 3-hydroxypyridin-4-one (HPO) iron chelators on cell cycle arrest with subsequent cycle synchronization has been compared with that of the hexadentate desferrioxamine (DFO) in K562 and Daudi cells. The relationships between chelator concentration and inhibition of growth, DNA synthesis and ribonucleotide reductase, and phase of cell cycle arrest have also been explored. H...

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Evaluation of Liver Toxicity of 2-Methyl-3-Hydroxypyridin-4-one in Iron Overloaded Rats

      Hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (DFO). In the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (MHPO), was studied in iron overloaded rats and compared with those of DFO. For iron overloading, rats received i.p. ...

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Relative Oral Efficacy and Acute Toxicity of Hydroxypyridin-4-One Iron Chelators in Mice

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin4one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing “Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded...

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ژورنال

عنوان ژورنال: Blood

سال: 1991

ISSN: 0006-4971,1528-0020

DOI: 10.1182/blood.v77.9.2049.2049