Superoxide and Nitric Oxide in Pathological Conditions Associated with Iron Overload. The Effects of Antioxidants and Chelators

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Abstract:

Free radicals are a one of damaging factors in diseases associated with iron overload. This review considers two principal questions: the mechanisms of free radical-mediated damage in cells and tissue and findings concerning the discovery of iron-stimulated free radical cascades in thalassemia and Fanconi anemia. There are two major precursors of all reactive oxygen and nitrogen species formed in living organism - superoxide (O2.-) and nitric oxide (NO). However, it has been shown that in addition to well-known mechanisms of the formation of reactive hydroxyl radicals and peroxynitrite from superoxide and NO, there are signal pathways by which these "physiological" radicals directly induce apoptosis, proton leak in mitochondria and an increase in oxygen consumption leading to cell death. In present review the mechanisms of free radical damage are considered with the particular emphasis of iron-induced free radical formation in thalassemia and Fanconi anemia. Furthermore free radical reactions leading to lipid peroxidation, LDL oxidation, the stimulation of apoptosis and other damaging processes are discussed. An importance of the chelating and antioxidant treatments of thalassemic and Fanconi anemia patients is also considered within the context of free radical damage and its prevention.

Keywords: fanconi anemia; free radical; iron overload; no; superoxide; thalassemia

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/092986705774462941

Affiliations: Vitamin research institute, Nauchny pr.14A, Moscow 117820, Russia.

Publication date: November 1, 2005

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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