Iron Chelation (iron + chelation)

Distribution by Scientific Domains

Terms modified by Iron Chelation

  • iron chelation therapy

  • Selected Abstracts


    Iron chelation prevents lung injury after major hepatectomy

    HEPATOLOGY RESEARCH, Issue 8 2010
    Konstantinos Kalimeris
    Aim:, Oxidative stress has been implicated in lung injury following ischemia/reperfusion and resection of the liver. We tested whether alleviating oxidative stress with iron chelation could improve lung injury after extended hepatectomy. Methods:, Twelve adult female pigs subjected to liver ischemia for 150 min, 65,70% hepatectomy and reperfusion of the remnant liver for 24 h were randomized to a desferrioxamine (DF) group (n = 6) which received i.v. desferrioxamine to a total dose of 100 mg/kg during both ischemia and reperfusion, and a control (C) group (n = 6). We recorded hemodynamic and respiratory parameters, plasma interleukin-6 and malondialdehyde levels, as well as liver malondialdehyde and protein carbonyls content. Total non-heme iron was measured in lung and liver. Pulmonary tissue was evaluated histologically for its nitrotyrosine and protein carbonyls content and for superoxide dismutase (SOD) and platelet-activating factor acetylhydrolase (PAF-AcH) activities. Results:, Reperfusion of the remnant liver resulted in gradual deterioration of gas-exchange and pulmonary vascular abnormalities. Iron chelation significantly decreased the oxidative markers in plasma, liver and the lung and lowered activities of pulmonary SOD and PAF-AcH. The improved liver function was followed by improved arterial oxygenation and pulmonary vascular resistance. DF also improved alveolar collapse and inflammatory cell infiltration, while serum interleukin-6 increased. Conclusion:, In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation. [source]


    Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infection

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2006
    A. E. R. Kartikasari
    Abstract Background, Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. Materials and methods, Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. Results, An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. Conclusions, Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis. [source]


    Reversal of cardiac complications in thalassemia major by long-term intermittent daily intensive iron chelation

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003
    H. Miskin
    Abstract: Objectives: In patients with thalassemia major (TM) who are non-compliant with long-term deferoxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional siderosis. It was recently shown in a small group of TM patients with established cardiac damage that continuous 24-h DFO infusion via an indwelling intravenous (i.v.) catheter is effective in reversing cardiac toxicity. The aim of the present study was to evaluate the results with intermittent daily (8,10 h) i.v. DFO. Patients: Eight TM patients with cardiac complications treated with intensive intermittent DFO were retrospectively evaluated by the mean annual serum ferritin, radionucleated ventriculography and 24-h electrocardiography recordings. Results: The median age at diagnosis of cardiac disease was 17.5 yr (range 14,21), and the median follow-up time was 84 months (range, 36,120). In the majority of patients (seven of eight) high-dose DFO (mean 95 ± 18.3 mg/kg/d) was administered via a central venous line. During follow-up, there was a significant decrease in the mean ferritin levels (5828 ± 2016 ng/mL to 1585 ± 1849 ng/mL, P < 0.001). Both cardiac failure (mean ejection fraction 32 ± 5) and cardiac arrhythmias were resolved in four of five patients. One non-compliant patient died during the follow-up. Following discontinuation of the i.v. therapy, compliance with conventional DFO therapy improved. The complications of this regimen, mainly catheter-related infections and catheter-related thrombosis, were similar to those described earlier. Conclusions: These results with the longest follow-up period in the literature suggest that i.v. high-dose DFO for 8,10 h daily may be as effective as continuous 24-h infusion for the reversal of established cardiac disease in TM. [source]


    Understanding the binding properties of an unusual metal-binding protein , a study of bacterial frataxin

    FEBS JOURNAL, Issue 16 2007
    Chiara Pastore
    Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe,S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study of the binding properties of CyaY, the bacterial ortholog of frataxin, to different divalent and trivalent cations, using NMR and X-ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets, but exposed glutamates and aspartates, which are residues that are unusual for iron chelation when not assisted by histidines and/or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function. [source]


    Iron chelation prevents lung injury after major hepatectomy

    HEPATOLOGY RESEARCH, Issue 8 2010
    Konstantinos Kalimeris
    Aim:, Oxidative stress has been implicated in lung injury following ischemia/reperfusion and resection of the liver. We tested whether alleviating oxidative stress with iron chelation could improve lung injury after extended hepatectomy. Methods:, Twelve adult female pigs subjected to liver ischemia for 150 min, 65,70% hepatectomy and reperfusion of the remnant liver for 24 h were randomized to a desferrioxamine (DF) group (n = 6) which received i.v. desferrioxamine to a total dose of 100 mg/kg during both ischemia and reperfusion, and a control (C) group (n = 6). We recorded hemodynamic and respiratory parameters, plasma interleukin-6 and malondialdehyde levels, as well as liver malondialdehyde and protein carbonyls content. Total non-heme iron was measured in lung and liver. Pulmonary tissue was evaluated histologically for its nitrotyrosine and protein carbonyls content and for superoxide dismutase (SOD) and platelet-activating factor acetylhydrolase (PAF-AcH) activities. Results:, Reperfusion of the remnant liver resulted in gradual deterioration of gas-exchange and pulmonary vascular abnormalities. Iron chelation significantly decreased the oxidative markers in plasma, liver and the lung and lowered activities of pulmonary SOD and PAF-AcH. The improved liver function was followed by improved arterial oxygenation and pulmonary vascular resistance. DF also improved alveolar collapse and inflammatory cell infiltration, while serum interleukin-6 increased. Conclusion:, In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation. [source]


    Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders

    MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2006
    Silvia Mandel
    Abstract Neurodegeneration in Parkinson's, Alzheimer's, or other neurodegenerative diseases appears to be multifactorial, where a complex set of toxic reactions, including oxidative stress (OS), inflammation, reduced expression of trophic factors, and accumulation of protein aggregates, lead to the demise of neurons. One of the prominent pathological features is the abnormal accumulation of iron on top of the dying neurons and in the surrounding microglia. The capacity of free iron to enhance and promote the generation of toxic reactive oxygen radicals has been discussed numerous times. The observations that iron induces aggregation of inert ,-synuclein and beta-amyloid peptides to toxic aggregates have reinforced the critical role of iron in OS-induced pathogenesis of neurodegeneration, supporting the notion that a combination of iron chelation and antioxidant therapy may be one significant approach for neuroprotection. Tea flavonoids (catechins) have been reported to possess divalent metal chelating, antioxidant, and anti-inflammatory activities, to penetrate the brain barrier and to protect neuronal death in a wide array of cellular and animal models of neurological diseases. This review aims to shed light on the multipharmacological neuroprotective activities of green tea catechins with special emphasis on their brain-permeable, nontoxic, transitional metal (iron and copper)-chelatable/radical scavenger properties. [source]


    Identification of hypoxia-inducible factor-1, (HIF-1,) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradation

    THE PROSTATE, Issue 3 2005
    Xinyu S. Fu
    Abstract BACKGROUND Hypoxia-inducible factor-1, (HIF-1,) regulates cellular responses to hypoxia and is rapidly degraded under normoxia through von Hippel-Lindau (VHL) mediated ubiquitination. Although HIF-1, stabilization appears to be the molecular basis for VHL-associated cancers, stabilizing mutations in HIF-1, have not been reported. METHODS A series of 15 metastatic androgen independent prostate cancers were examined for mutations in the oxygen-dependent domain (ODD) of HIF-1, by PCR amplification and DNA sequencing. RESULTS A somatic proline to serine mutation in codon 582 (P582S) was identified in one sample. Transfection studies with a HIF-1, regulated reporter gene showed increased transcriptional activity that correlated with higher mutant HIF-1, protein expression. Increased expression of the P582S mutant induced by iron chelation, which blocks proline hydroxylation of wild-type HIF-1,, was markedly attenuated. The mutant also showed increased stability under normoxic versus hypoxic conditions. CONCLUSION The P582S HIF-1, is a stable variant and HIF-1, mutation is a mechanism for enhancing HIF-1, activity in human cancer. The recent identification of the identical P582S HIF-1, as a polymorphism suggests that this variant may increase tumor susceptibility or cause more aggressive biological behavior. © 2004 Wiley-Liss, Inc. [source]


    In vivo Skin Irritation Potential of a Castanea sativa (Chestnut) Leaf Extract, a Putative Natural Antioxidant for Topical Application

    BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2008
    Isabel F. Almeida
    However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40°. The IC50 found for the iron chelation and DPPH scavenging assays were 132.94 ± 9.72 and 12.58 ± 0.54 µg/ml (mean ± S.E.M.), respectively. The total phenolic content was found to be 283.8 ± 8.74 mg GAE/g extract (mean ± S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application. [source]


    Effects of radio frequency magnetic fields on iron release from cage proteins

    BIOELECTROMAGNETICS, Issue 5 2009
    Oscar Céspedes
    Abstract Ferritin, the iron cage protein, contains a superparamagnetic ferrihydrite nanoparticle formed from the oxidation and absorption of Fe2+ ions. This nanoparticle increases its internal energy when exposed to alternating magnetic fields due to magnetization lag. The energy is then dissipated to the surrounding proteic cage, affecting its functioning. In this article we show that the rates of iron chelation with ferrozine, an optical marker, are reduced by up to a factor of 3 in proteins previously exposed to radio frequency magnetic fields of 1 MHz and 30 µT for several hours. The effect is non-thermal and depends on the frequency-amplitude product of the magnetic field. Bioelectromagnetics 30:336,342, 2009. © 2009 Wiley-Liss, Inc. [source]


    Oak leaf extract as topical antioxidant: Free radical scavenging and iron chelating activities and in vivo skin irritation potential

    BIOFACTORS, Issue 4 2008
    Isabel F. Almeida
    Abstract The topical application of antioxidants may be beneficial for the protection of the skin against UV damage. An extract of Quercus robur leaves was prepared and evaluated considering its putative application as topical antioxidant. The solvent and extractive method selection was monitored by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron chelating activity and the phenolic composition (HPLC/DAD) were assessed on the extract obtained under optimized conditions. Skin irritation potential was investigated by performing an in vivo patch test in 19 volunteers. The extraction solvent which resulted in the highest activity was ethanol:water (4:6) and thus it was selected for further preparation of this extract. The IC50a for the iron chelation and DPPH scavenging assays were 153.8 ± 26.3 ,g.mL,1 and 7.53 ± 0.71 ,g.mL,1 (mean ± SD), respectively. The total phenolic content was found to be 346.3 ± 6.7 mg gallic acid equivalents (GAE)/g extract (mean ± SD). Three phenolic compounds were identified in the extract namely: ellagic acid, rutin and hyperoside. The major identified component was ellagic acid. The patch test carried out showed that the extract can be regarded as safe for topical application. [source]


    Myocardial iron clearance during reversal of siderotic cardiomyopathy with intravenous desferrioxamine: a prospective study using T2* cardiovascular magnetic resonance

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2004
    Lisa J. Anderson
    Summary Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal of siderotic cardiomyopathy has been reported. In order to determine the changes in myocardial iron during treatment, we prospectively followed thalassaemia patients commencing intravenous desferrioxamine for iron-induced cardiomyopathy during a 12-month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months of treatment, and included left ventricular (LV) function and myocardial and liver T2*, which is inversely related to iron concentration. One patient died. The six survivors showed progressive improvements in myocardial T2* (5·1 ± 1·9 to 8·1 ± 2·8 ms, P = 0·003), liver iron (9·6 ± 4·3 to 2·1 ± 1·5 mg/g, P = 0·001), LV ejection fraction (52 ± 7·1% to 63 ± 6·4%, P = 0·03), LV volumes (end diastolic volume index 115 ± 17 to 96 ± 3 ml, P = 0·03; end systolic volume index 55 ± 16 to 36 ± 6 ml, P = 0·01) and LV mass index (106 ± 14 to 95 ± 13, P = 0·01). Iron cleared more slowly from myocardium than liver (5·0 ± 3·3% vs. 39 ± 23% per month, P = 0·02). These prospective data confirm that siderotic heart failure is often reversible with intravenous iron chelation with desferrioxamine. Myocardial T2* improves in concert with LV volumes and function during recovery, but iron clearance from the heart is considerably slower than from the liver. [source]


    The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1

    CANCER SCIENCE, Issue 5 2009
    Junko H. Ohyashiki
    To evaluate the effect of deferasirox in human myeloid leukemia cells, and to identify the moleclular pathways responsible for antiproliferative effects on leukemia cells during chelation therapy, we performed gene expression profiling to focus on the pathway involved in the anticancer effect of deferasirox. The inhibitory concentration (IC50) of deferasirox was 17,50 µM in three human myeloid cell lines (K562, U937, and HL60), while those in fresh leukemia cells obtained from four patients it varied from 88 to 172 µM. Gene expression profiling using Affymerix GeneChips (U133 Plus 2.0) revealed up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) encoding p21CIP, genes regulating interferon (i.e. IFIT1). Pathways related to iron metabolism and hypoxia such as growth differentiation factor 15 (GDF-15) and Regulated in development and DNA damage response (REDD1) were also prominent. Based on the results obtained from gene expression profiling, we particularly focused on the REDD1/mTOR (mammalian target of rapamycin) pathway in deferasirox-treated K562 cells, and found an enhanced expression of REDD1 and its down-stream protein, tuberin (TSC2). Notably, S6 ribosomal protein as well as phosphorylated S6, which is known to be a target of mTOR, was significantly repressed in deferasirox-treated K562 cells, and REDD1 small interfering RNA restored phosphorylation of S6. Although iron chelation may affect multiple signaling pathways related to cell survival, our data support the conclusion that REDD1 functions up-stream of tuberin to down-regulate the mTOR pathway in response to deferasirox. Deferasirox might not only have benefit for iron chelation but also may be an antiproliferative agent in some myeloid leukemias, especially patients who need both iron chelation and reduction of leukemia cells. (Cancer Sci 2009; 100: 970,977) [source]