Importance of Iron Chelation in Free Radical-Induced Oxidative Stress and Human Disease

Klaudia      Jomova; Marian      Valko

Abstract

Iron is a redox active metal involved in the oxidation-reduction reactions and regulation of cell growth and differentiation. Iron is an integral part of many proteins and enzymes that maintains various physiological functions. Most of the human bodys iron is contained in red blood cells. Despite iron being an abundant trace metal in food, millions of people worldwide suffer from anemia. Iron deficiency results in impaired production of iron-containing proteins and inhibition of cell growth. In contrast, abnormal iron uptake has been related to the most common hereditary disease hemochromatosis, leading to tissue damage derived from free radical toxicity. In addition, disruption of iron regulation plays a key role in the etiology of Alzheimers disease, Parkinsons disease, Huntingtons disease, Friedreichs ataxia and other neurological disorders, cancer (lung cancer, breast cancer, colon cancer), Fanconi anemia, stroke and ageing. Thus the control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease. The most frequent is the toxic role of iron linked with the catalytic decomposition of hydrogen peroxide (Fenton reaction) leading to the formation of reactive oxygen species (ROS) causing damage to biomolecules, including lipids, proteins and DNA. The binding of irondesigned chelators via nitrogen, oxygen or sulphur donor atoms blocks iron ’ s ability to catalyze the formation of free radicals. Thus the design of various metal chelators to prevent free radical reactions is an important approach in the treatment of many iron-related diseases. The development of effective dual functioning antioxidants, possessing both metal-chelating and free radical-scavenging properties is awaited. The aim of this review is to discuss the role of iron and importance of iron-chelation in human disease and ageing.

Keywords: Iron homeostasis, redox-active metals, fenton reaction, reactive oxygen species (ROS), metal chelators, iron toxicity, aging, antioxidants, cell division, endosomes