Iron metabolism, free radicals, and oxidative injury.
Iron has the capacity to accept and donate electrons readily. This capability makes it physiologically essential, as a useful component of cytochromes and oxygen-binding molecules. However, iron is also biochemically dangerous; it can damage tissues by catalyzing the conversion of hydrogen peroxide to free-radical ions that attack cellular membranes, protein and DNA. This threat is reduced in the healthy state where, because of the fine iron metabolism regulation, there is never appreciable concentration of 'free iron'. Under pathological conditions, iron metabolism and superoxide metabolism are clearly interactive. Each can exacerbate the toxicity of the other. Iron overload may amplify the damaging effects of superoxide overproduction in a very broad spectrum of inflammatory, both acute and chronic, conditions. Furthermore, chronic oxidative stress may modulate iron uptake and storage, leading to a self-sustained and ever-increasing spiral of cytotoxic and mutagenic events. The iron chelator deferroxamine is able to chelate 'free iron' even inside the cell. Its regular clinical use is to promote the excretion of an iron overload, when phlebotomy is harmful, and the dosage varies between 2-10 g/d. In conditions where deferroxamine is used to prevent the iron-driven oxygen toxicity, i.e., acute or chronic inflammatory diseases with oxidative stress, the dosage can be extremely reduced and the addition of antioxidants could be useful.
Emerit
J
J
Service de Biochimie, Hĵpital Saint-Joseph, Paris, France. Emerit@wanadoo.fr
Beaumont
C
C
Trivin
F
F
D000975:Antioxidants / Q000627:therapeutic use; D003676:Deferoxamine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005609:Free Radicals / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy; D018384:Oxidative Stress / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D007502:Iron Chelating Agents; D013481:Superoxides; D006861:Hydrogen Peroxide; D007501:Iron; D003676:Deferoxamine