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Blood Cells Mol Dis. 2016 Sep;60:36-43. doi: 10.1016/j.bcmd.2016.05.004. Epub 2016 May 8.

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

Author information

1
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA.
2
Departments of Genetics and Complex Diseases and Nutrition, Harvard School of Public Health, Boston, MA.
#
Contributed equally

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.

KEYWORDS:

Ferroportin; Hemoglobinopathy; Hepcidin; Iron; Thalassemia

PMID:
27519943
PMCID:
PMC5094460
DOI:
10.1016/j.bcmd.2016.05.004
[Indexed for MEDLINE]
Free PMC Article

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