Iron Toxicity and Chelation Therapy

  title={Iron Toxicity and Chelation Therapy},
  author={Robert S. Britton and Katherine L. Leicester and Bruce R. Bacon},
  journal={International Journal of Hematology},
Iron is an essential mineral for normal cellular physiology, but an excess can result in cell injury. Iron in low-molecular-weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates; the result is wide-ranging impairment in cellular function and integrity. The rate of free radical production must overwhelm the cytoprotective defenses of cells before injury… 

A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction

The data suggest that free iron released by HO-1 causes mitochondrial dysfunction in pathological situations accompanied by endotoxic shock.

Iron homeostasis, hepatocellular injury, and fibrogenesis in hemochromatosis: the role of inflammation in a noninflammatory liver disease.

This review highlights recent advances in identifying major regulators associated with hepatic iron homeostasis and examines the potential mechanisms involved in the development of iron overload-induced hepatic injury and fibrogenesis.

Mammalian Iron Metabolism

  • L. Valerio
  • Biology
    Toxicology mechanisms and methods
  • 2007
This review will address the regulatory mechanisms of normal iron metabolism in mammals with emphasis on dietary exposure and the identification of deficiencies so that future metabolic or toxicological studies may be appropriately focused.

Prospects for introducing deferiprone as potent pharmaceutical antioxidant.

In vitro, in vivo and clinical data suggest that L1 is the most potent drug antioxidant because of its high therapeutic index, ability to reach extracellular and intracellular compartments of many tissues and ability to inhibit both iron and copper catalysed free radical reactions.

Liposomal Antioxidants for Protection against Oxidant-Induced Damage

Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules.

Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or random free radical reaction?

Oxidative stress and antioxidant response to subacute and subchronic iron overload in Wistar rat

Data are virtually significant in elucidating the higher magnitude of subchronic than subacute iron overload in initiating oxidative stress and antioxidant defense and both pathways proceeded in a time-dependent rather than dose-dependent manner.



Metal-induced hepatotoxicity.

There are few data addressing the key issue of whether free radical production is increased in patients with iron or copper overload, and it seems likely that lipid peroxidation is involved, since similar functional defects are produced by metal-induced lipidperoxidation in these organelles in vitro.

Molecular bases of cellular iron toxicity.

Identification of thiolic sarcolemmal proteins as a primary target of iron toxicity in cultured heart cells.

It is shown that iron toxicity in myocyte cultures is associated with profound, and reproducible changes in contractility and electophysiologic behaviour, and iron toxicity may be significantly modified by the use of antioxidants such as α-tocopherol, by ascorbic acid, or by simultaneous hypoxia.

Iron-induced peroxidative injury to isolated rat hepatic mitochondria.

Pathophysiology of Iron Overload a

In thalassemia, iron overload is the joint outcome of excessive iron absorption and transfusional siderosis, manifested clinically in fatal hemosiderotic cardiomyopathy and at suboptimal concentrations is a pro‐oxidant, enhancing the catalytic effect of iron in free radical formation.

Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells.

The effect of iron overload on rat plasma and liver oxidant status in vivo.

The data demonstrate that IO causes lipid metabolism disturbances and oxidative stress which is associated with substantial depletion of endogenous antioxidants and moderate lipid peroxidative damage.

Iron-induced liver injury.

Enhanced gamma-glutamyl transpeptidase expression and selective loss of CuZn superoxide dismutase in hepatic iron overload.