Iron overload

Transferrin is essential for movement of iron and without it, as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary atransferrinemia is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy (10). 

Ascorbic acid also forms soluble chelate complexes with iron (142—145). It seems ascorbic acid has no effect on high iron levels found in people with iron overload (146). It is well known, in fact, that ascorbic acid in the presence of iron can exhibit either prooxidant or antioxidant effects, depending on the concentration used (147). The combination of citric acid and ascorbic acid may enhance the iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of heart disease, cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. The synergistic combination of citric acid and ascorbic acid needs further study, particularly because the iron overload produced may be correctable (147). 

A molecule that binds iron through coordinating moieties (e.g., carboxylates or amines). They are used to inhibit iron-catalyzed free radical reactions or to treat iron overload conditions. Desferrioxamine and defer-iprone are two widely used iron chelators. 

Glycine, ethylene-N,N -bis-2-(0-hydroxyphenyl)-chelating agents iron overload, 6, 769 Glycine, glycyl-hydrolysis... 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

Siderophores like desferrioxamine may, therefore, find increasing applications not only in the treatment of iron poisoning and iron-overloaded disease states but also as chemotherapeutic agents, although the possible problems noted above cannot be ignored. 

Cavill, L, Staddon, G. and Jacobs, A. (1972). Iron kinetics in the skin of patients with iron overload. J. Invest. Dermatol. 58, 96-98. 

Iron overload is known to be toxic and potentially fatal. The major pathological effects of hepatic iron overload are fibrosis and cirrhosis, and hepatocellular carcinoma (Bonkovsky, 1991). The role of free radicals in the pathology of hepatic iron overload has been the subject of a detailed review recently (Bacon and Britton, 1990). 

Treatment with iron chelators and a-tocopherol protect against lipid p>eroxidation and hepatocellular injury in iron-overloaded rats (Sharma etal., 1990). When hepatocytes are isolated from rats, which have been pretreated with a-tocopherol, there is a significant reduction in iron-induced lipid peroxidation and improvement in cell viability in vitro (Poli et al., 1985). Similar effects were seen when hepatocytes were incubated with iron chelators (Bacon and Britton, 1990). Treatment of moderately, but not heavily, iron-loaded rats with desferrioxamine in vivo inhibits the pro-oxidant activity of hepatic ultrafiltrates (Britton et al., 1990b). 

Bacon, B.R. and Britton, R.S. (1989). Hepatic injury in chronic iron overload role of lipid peroxidation. Chem. Biol. Interact. 70, 183-226. 

Bacon, B.R, Tavill, A.S., Brittenham, G.M., Park, C.H. and Recknagel, R.O. (1983a). Hepatic lipid peroxidation in vivo rats with chronic iron overload. J. Clin. Invest. 71, 429-439. 

Britton, R.S., O Neill, R. and Bacon, B.K (1990a). Hepatic mitochondrial malonedialdehyde metabolism in rats with chronic iron overload. Hepatology 11, 93-97. 

Britton, R.S., Ferrali, M., Magieri, C.J., Recknagel, R.O. and Bacon B.R, (1990b). Increased prooxidant action of hepatic cytosolic low-molecular-weight iron in experimental iron overload. Hepatology 11, 1038-1043. 

Peters, S.W., Jones, B.M., Jacobs, A. and Wagstaff, M. (1985). Free iron and lipid peroxidation in the plasma of patients with iron overload. In Proteins of Iron Storage and Transport (eds. G. Spik, J. Montreuil, R.R. Crichton and J. Mazurier) pp. 321-324. Elsevier Science Publishers, New York. 

Selden, C., Seymour, C.A. and Peters, T.J. (1980). Activities of some free radical scavenging enzymes and glutathione concentrations in human and rat liver and their relationship to the pathogenesis of tissue damage in iron overload. Clin. Sci. 58, 211-219. 

Siegers, C.P., Bumann, D., Trepkau, H.D., Schadwinkel, B. and Bareytton, G. (1992). Influence of dietary iron overload on cell proliferation and intestinal tumorigenesis in mice. Cancer Lett. 65, 245-249. 

Retinopathy of prematurity Dietary iron overload (red wine, beer brewed in iron pots) Idiopathic haemochromatosis... 

Iron Overload and Liver Injury 238 3.10 Ischaemic Hepatitis 243... 

A particular instance of iron overload being associated with liver injury, with free radicals again being implicated, is the hepatic porphyria and hepatocarcinoma induced by polyhalogenated aromatic chemicals. This is described separately below. 

Hereditary hemochromatosis is an autosomal recessive disease of increased intestinal iron absorption and deposition in hepatic, cardiac, and pancreatic tissue. Hepatic iron overload results in the development of fibrosis, hepatic scarring, cirrhosis, and hepatocellular carcinoma. Hemochromatosis can also be caused by repeated blood transfusions, but this mechanism rarely leads to cirrhosis. 

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