During cold storage of donor hearts, reactive oxygen species produced by intracellular redox-active chelatable iron potentially alter myocardial function. To reduce this cold-induced injury we investigated the efficacy of two new modifications of the well established histidine-tryptophan-ketogluterate (HTK) solution (Custodiol) with the addition of N-alpha-acetyl-l-histidine and iron-chelators ...

Mitochondria-targeted peptides incorporating dual fluorescent and selective iron chelators have been designed as novel biosensors for the mitochondrial labile iron pool. The probes were demonstrated to specifically co-localize with mitochondria and their fluorescence emission was found to be sensitive to the presence of iron.

Iron-mediated carcinogenesis is thought to occur through the generation of oxygen radicals. Iron chelators are used in attempts to prevent the long term consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), has shown promise as an effective chelator. Using an established hepatocellular model of iron overload, we studied the generation of iron-catalyzed oxidative ...

The therapeutic effect of iron (Fe) chelators on the potentially toxic plasma pool of nontransferrin-bound iron (NTBI), often present in Fe overload diseases and in some cancer patients during chemotherapy, is of considerable interest. In the present investigation, several multidentate pyridinones were synthesized and compared with their bidentate analogue, deferiprone (DFP; L1, orally active) ...

Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising effective iron chelators for the treatment of iron overload in -thalassemia patients; nonetheless, their side effects have also been reported. 3-Hydroxypyridinone derivatives are being developed as a safer new chelator and in combined chelation therapy. We evaluated the iron-chelating activity of 1-(N-acetyl-6-aminohe...

Background: Thalassemia is a series of hemoglobinopathies in which the production of perfect hemoglobin is completely or partially suppressed. Using injectable iron chelators have been dominating treatment for the iron overload caused by recurrent blood transfusions in thalassemic patients, however, a new oral iron chelating drug (Exjade) have been recently introduced and might be cost effec...

      Hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (DFO). In the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (MHPO), was studied in iron overloaded rats and compared with those of DFO. For iron overloading, rats received i.p. ...

Although anthracyclines such as doxorubicin are widely used antitumor agents, a major limitation for their use is the development of cardiomyopathy at high cumulative doses. This severe adverse side effect may be due to interactions with cellular iron metabolism, because iron loading promotes anthracycline-induced cell damage. On the other hand, anthracycline-induced cardiotoxicity is significa...

Excessive iron is toxic to cells and organelles, where it can generate harmful reactive oxygen species (ROS) resulting in oxidative tissue damage. Liver is the major organ for iron storage and redox active iron in this tissue can cause fibrosis and cirrhosis in β-thalassemia patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are clinically approved iron chelators used for ...

Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were ...