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Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.

ABSTRACT: Hepcidin, a peptide produced in the liver, decreases intestinal iron absorption and macrophage iron release by causing degradation of the iron exporter, ferroportin. Because its levels are inappropriately low in patients with iron overload syndromes, hepcidin is a potential drug target. We previously conducted a chemical screen that revealed ipriflavone, an orally available small molecule, as a potent inducer of hepcidin expression. To evaluate ipriflavone's effect on iron homeostasis, we placed groups of 5-week old wild type or thalassemia intermedia (Hbb(Th3+/-)) mice on a soy-free, iron-sufficient diet, AIN-93G containing 220mg iron and 0-750mgipriflavone/kg of food for 50days. Ipriflavone 500mg/kg significantly reduced liver iron stores and intestinal ferroportin expression in WT mice, while increasing the ratio of hepcidin transcript levels to liver iron stores. Ipriflavone supplementation in Hbb(Th3+/-) mice failed to alleviate iron overload and was associated with a milder reduction in intestinal ferroportin and a failure to alter the ratio of hepcidin transcript levels to liver iron stores or splenic expression of the hepcidin-regulatory hormone, erythroferrone. These data suggest that dietary supplementation with ipriflavone alone would not be sufficient to treat iron overload in thalassemia intermedia.

SUBMITTER: Patchen B

PROVIDER: S-EPMC5094460 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.

Patchen Bonnie B Koppe Tiago T Cheng Aaron A Seo Young Ah YA Wessling-Resnick Marianne M Fraenkel Paula G PG

Blood cells, molecules & diseases 20160508

Hepcidin, a peptide produced in the liver, decreases intestinal iron absorption and macrophage iron release by causing degradation of the iron exporter, ferroportin. Because its levels are inappropriately low in patients with iron overload syndromes, hepcidin is a potential drug target. We previously conducted a chemical screen that revealed ipriflavone, an orally available small molecule, as a potent inducer of hepcidin expression. To evaluate ipriflavone's effect on iron homeostasis, we placed ...[more]

PMID: 27519943

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Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.

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Dietary supplementation with ipriflavone decreases hepatic iron stores in wild type mice.

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