Desferal

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F Desferal (Ciba-Geigy) J Desferal (Novartis-Takeda) mesylate)... 

The cytotoxicity of LDL can also be inferred from the study by Blake et al. (1985). In this study of human cultured endothelial cells, stored sera from patients with necrotizing arteritis demonstrated an enhanced tendency to develop oxidized LDL, which correlated closely with endothelial cell cytotoxicity. This process appears to require the presence of both oxygen and transition metal ions such as iron in the presence of a reducing agent (Gebicki ef /., 1991). There is considerable evidence that transition metals are involved in cell-induced modifications of LDL including the inhibitory effects of EDTA and desfer-rioxamine (Hiramatsu et 1987). A role for Of in LDL modification by endothelial cells and fibroblasts comes from studies showing inhibition of LDL oxidation by SOD (Steinbrecher, 1988). 

Siderophores are iron-complexing compounds of low molecular weight that are synthesized by bacteria and fungi, and serve to deliver iron to the microbes. Because of their exclusive affinity and specificity for Fe3+, natural siderophores and synthetic derivatives have been exploited in the treatment of human iron-overload diseases. The most successfully used example is Desferal , which is the methane sulfonate derivative of iron-free ferrioxamine B, a linear trihydroxamate (Figure 3.2). Ferrioxamine was isolated in 1958 from the culture supernatant of Streptomyces... 

Chelators of iron, which are now widely applied for the treatment of patients with thalassemia and other pathologies associated with iron overload, are the intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI) (Figure 19.23, see also Chapter 31). Desferrioxamine (DFO) belongs to a class of natural compounds called siderophores produced by microorganisms. The antioxidant activity of DFO has been studied and compared with that of synthetic hydroxypyrid-4-nones (LI) and classic antioxidants (vitamin E). It is known that chronic iron overload in humans is associated with hepatocellular damage. Therefore, Morel et al. [370] studied the antioxidant effects of DFO, another siderophore pyoverdin, and hydroxypyrid-4-ones on lipid peroxidation in primary hepatocyte culture. These authors found that the efficacy of chelators to inhibit iron-stimulated lipid peroxidation in hepatocytes decreased in the range of DFO > hydroxypyrid-4-ones > pyoverdin. It seems that other siderophores are also less effective inhibitors of lipid peroxidation than DFO [371],... 

The most successful up-to-date treatment of thalassemic patients is chelating therapy, which is based on patient s lifetime application of iron chelators. Removal of excess iron is supposed to be effective route for suppressing free radical-mediated damage. There is a great number of studies showing successful treatment of thalassemic patients with intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI). Biochemical studies show the efficacy of both chelators in removal of excess iron. For example, the incubation of thalassemic erythrocytes with 0.5 mmol 1 1 LI during 6h resulted in 96% removal of membrane-free iron [392], It was demonstrated that LI is able to remove pathologic deposits of... 

Unfortunately, the iron complexes of both chelators desferal and LI are able to catalyze the formation of oxygen radicals [394,395]. Cragg et al. [395] also showed that LI exposure markedly enhanced free radical-mediated DNA damage in iron-loaded liver cells. It has been suggested that the prooxidantrantioxidant ratio of LI activity depends on the composition of complexes formed a 1 3 Fe/Ll is supposed to be inactive in the production of free radicals while the generation of radicals is possible at lower Fe/Ll ratios [395], But it should be noted that in real biological systems there is always equilibrium between iron-chelator complexes of different composition. 

The choice of iron chelators on the basis of both molecular and cellular criteria was discussed in 2003 (374). One 2005 review is concerned with the design of orally active iron chelators (375), another considers the prospects for effective clinical use of several hydro-x5rpyridinones, dealing with novel species such as the 1-allyl compound as well as with the established deferiprone (LI) and desferrioxamine (Desferal, DFO) (376). A review dated 2006 deals with relevance of iron mobilization from both transferrin and other iron-containing proteins by LI to the treatment of various anemias and other iron-overload conditions (377). Two 2007 reviews concentrate on LI, as the only hydroxypyridinone in general clinical use. One author concludes that, on balance, LI is to be preferred to DFO. This conclusion is on the grounds that, despite the not infrequent occurrence of minor side effects, the incidence of serious side effects... 

Avlosulfone, Eporal, Diphenasone, Udolac Cerubidine, Daunoblastin, Ondena Desferal Rescriptor... 

Deferoxamine (Desferal ) has a specific ability to chelate iron and is useful in treating acute iron intoxication. Deferoxamine can be administered... 

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