Iron Overload Mechanisms and Therapeutic Strategies

Iron is vital for oxygen transport, enzymatic reactions and cellular metabolism, yet its redox activity renders excess iron cytotoxic. Under normal conditions, dietary iron is absorbed in the duodenum, bound to transferrin in plasma, stored in ferritin and regulated by the hormone hepcidin. In hereditary haemochromatosis and transfusion-dependent anaemias, hepcidin deficiency or repeated parenteral iron leads to transferrin saturation and emergence of non-transferrin-bound iron (NTBI). NTBI comprises diverse low- and high-molecular-weight species that catalyse formation of reactive oxygen species (ROS), triggering lipid peroxidation, mitochondrial damage and ferroptotic cell death. Progressive iron deposition in the liver, heart, pancreas and endocrine glands precipitates fibrosis, cardiomyopathy and diabetes. Standard management includes phlebotomy where feasible and iron chelation therapy using deferoxamine, deferiprone or deferasirox to enhance urinary and biliary iron excretion. Emerging strategies aim to modulate hepcidin–ferroportin axis with agonists or hepcidin mimetics, develop next-generation oral chelators with improved tissue penetration and design nanoparticle-based delivery systems. Adjunctive antioxidants and inhibitors of ferroptosis are being explored to protect vulnerable tissues. Integrative approaches combining molecular therapies, advanced diagnostics for NTBI speciation and patient-tailored chelation regimens promise to refine long-term outcomes and reduce global disease burden.

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Iron Overload Mechanisms and Therapeutic Strategies publication trend

The graph below shows the total number of articles in iron overload mechanisms and therapeutic strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Transferrin: Plasma glycoprotein that binds iron in a non-redox state and delivers it to cells via receptor-mediated uptake.

Non-transferrin-bound iron (NTBI): Labile pool of iron species appearing once transferrin is saturated, capable of catalysing free-radical formation.

Ferroptosis: Regulated cell-death pathway driven by iron-dependent lipid peroxidation and accumulation of reactive oxygen species.

Chelation therapy: Medical treatment employing ligands that form stable complexes with excess iron to facilitate its excretion.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can inflict oxidative damage when produced in excess.

References

1. The clinical relevance of detectable plasma iron species in iron overload states and subsequent to intravenous iron‐carbohydrate administration. American Journal of Hematology (2023).
2. Increased Levels of Circulating Iron-Albumin Complexes in Peripheral Arterial Disease Patients. Antioxidants (2023).
3. The (Bio)Chemistry of Non-Transferrin-Bound Iron. Molecules (2022).