Abstract
Background Iron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution, as it can catalyze the generation of hydroxyl radical and strong evidence supports its involvement, combined with reactive oxygen species, in a wide range of diseases. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases.
Results Here we develop a dynamic model of mouse iron distribution including regulation by hepcidin and use it to fit existing data from different diets. The model is able to fit data for adequate and low iron diets but has considerable deviations from the data for a rich iron diet. Namely the model predicts more iron in red blood cells and less iron in the liver than what was observed in experiments.
Conclusions The implication of these results is that hepcidin alone is not sufficient to regulate iron homeostasis in high iron conditions and that other factors are important. The model was able to simulate anemia when hepcidin was increased but was unable to simulate hemochromatosis when hepcidin was suppressed, supporting the view that in high iron conditions additional regulatory interactions are important.
