Superoxide and nitric oxide in pathological conditions associated with iron overload: the effects of antioxidants and chelators.
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 (O(2)( -)) 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.
Afanas'ev
I B
IB
Vitamin Research Institute, Nauchny pr.14A, Moscow 117820, Russia. iafan@aha.ru
D000975:Antioxidants / Q000627:therapeutic use*; D005199:Fanconi Anemia / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013789:Thalassemia / Q000188:drug therapy / Q000378:metabolism
D000975:Antioxidants; D007502:Iron Chelating Agents; D013481:Superoxides; D009569:Nitric Oxide