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Abstract
SUMMARY
B-thalassemia major is a sever transfusion dependent form of thalassemias. The consequent chronic anemia leads to increased dietary iron absorption rsulting in iron overload. Moreover, treatment through regular blood transfusion adds more iron from hemoglobin.
As there is no natural means for the body to eliminate the excess iron, the progressive increase in iron load results in dsmsge to many organs. In addition to the organ damage, excess iron can also lead to DNA damage by catalyzing the production of reactive oxygen species within the cell, leading to the induction of DNA base damage, gene mutations and chromosomal aberrations in mammalian cells.
For these patients, the use of chelating agents, may protect not only against iron-induced organ damage but also against the excessive iron-catalysed, oxidative DND damage.
Currently there are two iron chelating agents available for the management of iron overload in thalassaemia:deferoxamine, which needs to be administered parenterally, and deferiprone, which has the advantage that it is taken orally. Both agents have been shown to have antioxidant and cytoprotective effects. On the other hand, some studies have indicated that these agents may have clastogenic effects. This clastogenic effect may reflect a non-genotoxic mechanism due to the chelation of iron from cellular systems that depend on iron for normal functioning. A likely candidate for this is ribonucleotide reductase, an important enzyme in DNA synthesis. It functions to supply balanced pools of precursors and is therefore critical during DNA replicative and repair synthesis. Deferiprone is known to inhibit this enzyme, which contains a labile iron prosthetic group.