Interplay between superoxide and nitric oxide in thalassemia and Fanconi's anemia.
Thalassemia (thal) and Fanconi's Anemia (FA) are genetic disorders associated with iron-catalyzed free radical damage. Therefore, the contemporary and most successful treatment of thalassemic patients depends on the application of iron (Fe) chelators. However, there is another pathway of free radical-mediated damaging processes in these pathologies, depending on the interplay between physiological free radicals superoxide and nitric oxide (NO). In the present study, we have considered the major routes of superoxide damaging effects in mitochondria: the initiation of apoptosis through the reduction of cytochrome c, the activation of uncoupled proteins by superoxide, and the mitochondrial damage due to the competition between superoxide and nitric oxide at the Complex IV site (cytochrome oxidase). The application of the effective scavengers superoxide dismutases and flavonoids for the treatment of thalassemic and FA patients, is discussed.
Vitamin Research Institute, Moscow, Russia. iafan@aha.ru
Igor B
IB
Afanas'ev
D017209:Apoptosis / Q000187:drug effects; D002384:Catalysis; D045304:Cytochromes c / Q000187:drug effects; D005199:Fanconi Anemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism* / Q000494:pharmacology; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
D005419:Flavonoids; D016166:Free Radical Scavengers; D005609:Free Radicals; D007502:Iron Chelating Agents; D013481:Superoxides; D009569:Nitric Oxide; D045304:Cytochromes c; D007501:Iron; D013482:Superoxide Dismutase