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  1. Iron Chelation

    Science.gov (United States)

    Skip to main content Menu Donate Treatments Therapies Iron Chelation Iron chelation therapy is the main treatment ... have iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you ...

  2. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats.

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    Suwakon Wongjaikam

    Full Text Available Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO, deferiprone (DFP and deferasirox (DFX or an antioxidant (N-acetyl cysteine (NAC with a combined DFP and NAC treatments on left ventricular (LV function with iron overload has not been investigated.Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day, DFP (75 mg/kg/day, DFX (20 mg/kg/day, NAC (100 mg/kg/day or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI, malondialdehyde (MDA, cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function.The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats.

  3. Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.

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    Theil, Elizabeth C

    2010-08-01

    Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.

  4. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

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    Pabla Aguirre

    Full Text Available Neuronal death in Parkinson's disease (PD is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.

  5. Oral iron chelators.

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    Kwiatkowski, Janet L

    2010-02-01

    Effective chelation therapy can prevent or reverse organ toxicity related to iron overload, yet cardiac complications and premature death continue to occur, largely related to difficulties with compliance in patients who receive parenteral therapy. The use of oral chelators may be able to overcome these difficulties and improve patient outcomes. A chelator's efficacy at cardiac and liver iron removal and side-effect profile should be considered when tailoring individual chelation regimens. Broader options for chelation therapy, including possible combination therapy, should improve clinical efficacy and enhance patient care.

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

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    Almeida, Isabel F; Valentão, Patrícia; Andrade, Paula B; Seabra, Rosa M; Pereira, Teresa M; Amaral, M Helena; Costa, Paulo C; Bahia, M Fernanda

    2008-01-01

    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 IC50s for the iron chelation and DPPH scavenging assays were 153.8 +/- 26.3 microg x mL-1 and 7.53 +/- 0.71 microg x 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.

  7. Antioxidant, Iron Chelating and Tyrosinase Inhibitory Activities of Extracts from Talinum triangulare Leach Stem

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    Ana Paula Oliveira Amorim

    2013-07-01

    Full Text Available The aim of this work is to evaluate the antioxidant activity against the radical species DPPH, the reducing capacity against Fe II ions, and the inhibitory activity on the tyrosinase enzyme of the T. triangulare. Hydromethanolic crude extract provided two fractions after the liquid/liquid partition with chloroform. The Folin-Ciocalteu method determined the total phenolic content of the crude extract (CE and the hydromethanolic fraction (Fraction 1, resulting in a concentration of 0.5853 g/100 g for Fraction 1, and 0.1400 g/100 g for the CE. Taking into account the results of the DPPH, the free radical scavenging capacity was confirmed. The formation of complexes with Fe II ions was evaluated by UV/visible spectrometry; results showed that CE has complexing power similar to the positive control (Gingko biloba extract.The inhibitory capacity of samples against the tyrosinase enzyme was determined by the oxidation of L-DOPA, providing IC50 values of 13.3 μg·mL−1 (CE and 6.6 μg·mL−1 (Fraction 1. The values indicate that Fraction 1 was more active and showed a higher inhibitory power on the tyrosinase enzyme than the ascorbic acid, used as positive control. The hydromethanolic extract of T. triangulare proved to have powerful antioxidant activity and to inhibit the tyrosinase enzyme; its potential is increased after the partition with chloroform.

  8. Iron chelating agents for iron overload diseases

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    Guido Crisponi

    2014-09-01

    Full Text Available Although iron is an essential element for life, an excessive amount may become extremely toxic both for its ability to generate reactive oxygen species, and for the lack in humans of regulatory mechanisms for iron excretion. Chelation therapy has been introduced in clinical practice in the seventies of last century to defend thalassemic patients from the effects of iron overload and, in spite of all its limitations, it has dramatically changed both life expectancy and quality of life of patients. It has to be considered that the drugs in clinical use present some disadvantages too, this makes urgent new more suitable chelating agents. The requirements of an iron chelator have been better and better defined over the years and in this paper they will be discussed in detail. As a final point the most interesting ligands studied in the last years will be presented.

  9. Iron Chelation and Multiple Sclerosis

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    Kelsey J. Weigel

    2014-01-01

    Full Text Available Histochemical and MRI studies have demonstrated that MS (multiple sclerosis patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

  10. Combination therapies in iron chelation

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    Raffaella Origa

    2014-12-01

    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  11. Importance of iron chelation therapy

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    A. Varoğlu

    2011-12-01

    Full Text Available It is necessary to remember that today patients have different options of chelation treatment, as desferrioxamine, deferiprone and deferasirox are available. However, a patient has to be compliant with treatments. They have always to remember that too much iron causes different complications and could be a barrier for a definitive cure from thalassemia. 由于出现了去铁胺、去铁酮和去铁斯若等药物,病人现在可以选择不同的螯合治疗方式。 然而,病人必须适应这几种治疗方式。 他们必须时刻记住太多的铁元素会引发多种并发症,并对地中海贫血的彻底治疗造成阻碍。

  12. Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays

    DEFF Research Database (Denmark)

    Lue, Bena-Marie; Nielsen, Nina Skall; Jacobsen, Charlotte;

    2010-01-01

    rutin compounds exhibited decreased reducing power and metal chelating abilities as compared to rutin. Conversely, investigations on the oxidation of human low density lipoprotein (LDL) revealed that rutin laurate was most effective in inhibiting oxidation by prolonging LDL lag time for an in vitro...

  13. Myelodysplastic Syndromes and Iron Chelation Therapy

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    Angelucci, Emanuele; Urru, Silvana Anna Maria; Pilo, Federica; Piperno, Alberto

    2017-01-01

    Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may, therefore, occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the scientific and clinical evidence for iron overload in MDS to better characterize the iron overload phenotype in these patients, which differs from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area. PMID:28293409

  14. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

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    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  15. Study on antioxidant activity of lipids with iron threonine chelate%苏氨酸铁螯合物对油脂的抗氧化活性研究

    Institute of Scientific and Technical Information of China (English)

    陶浚; 胡晓波; 孙文捷; 聂少平; 谢明勇

    2012-01-01

    摘要:采用Schaal烘箱法研究了氯化亚铁、苏氨酸铁螯合物、TBHQCL不同浓度苏氨酸铁螯合物对动植物油脂的抗氧化作用。实验结果表明,苏氨酸铁螯合物在添加剂量为0.5g/kg水平以上,对油脂具有催化自动氧化酸败的作用;但在油脂中添加剂量为0.1g/kg时能有效的降低油脂的过氧化值,表现出一定的抗氧化能力。%This experiment was studied the antioxidant activity of lipids with ferrous chloride,iron threonine chelate,TBHQ and the different concentration of iron threonine chelate by the method of Schaal oven. The results indicated that it could catalyze oxidation of chelate was more than 0.5g/kg. However,it could pids to rancidity when the dosage of the iron threonine effectively reduce the peroxide value at the dosage of 0.1 g/kg.

  16. Application of iron chelates in hydrodesulphurisation

    NARCIS (Netherlands)

    Wubs, Harm Jan

    1994-01-01

    Several iron chelate based methods for removing hydrogen sulphide from gas streams have been developed over the years. Notwithstanding the number of hydrodesulphurisation plants already in operation, the development of these processes has been more a kind of an art rather than a result of rational p

  17. Recent developments centered on orally active iron chelators

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    Robert Hider

    2014-09-01

    Full Text Available Over the past twenty years there has been a growing interest in the orally active iron chelators, deferiprone and deferasirox, both have been extensively studied. The ability of these compounds to mobilize iron from the heart and endocrine tissue has presented the clinician with some advantages over desferrioxamine, the first therapeutic iron chelator. Other orally active iron chelators are currently under development. The critical features necessary for the design of therapeutically useful orally active iron chelators are presented in this review, together with recent studies devoted to the design of such chelators. This newly emerging range of iron chelators will enable clinicians to apply iron chelation methodology to other disease states and to begin to design personalized chelation regimes.

  18. New developments and controversies in iron metabolism and iron chelation therapy.

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    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

  19. Iron chelators can protect against oxidative stress through ferryl heme reduction.

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    Reeder, Brandon J; Hider, Robert C; Wilson, Michael T

    2008-02-01

    Iron chelators such as desferrioxamine have been shown to ameliorate oxidative damage in vivo. The mechanism of this therapeutic action under non-iron-overload conditions is, however, complex, as desferrioxamine has properties that can impact on oxidative damage independent of its capacity to act as an iron chelator. Desferrioxamine can act as a reducing agent to remove cytotoxic ferryl myoglobin and hemoglobin and has recently been shown to prevent the formation of a highly cytotoxic heme-to-protein cross-linked derivative of myoglobin. In this study we have examined the effects of a wide range of iron chelators, including the clinically used hydroxypyridinone CP20 (deferriprone), on the stability of ferryl myoglobin and on the formation of heme-to-protein cross-linking. We show that all hydroxypyridinones, as well as many other iron chelators, are efficient reducing agents of ferryl myoglobin. These compounds are also effective at preventing the formation of cytotoxic derivatives of myoglobin such as heme-to-protein cross-linking. These results show that the use of iron chelators in vivo may ameliorate oxidative damage under conditions of non-iron overload by at least two mechanisms. The antioxidant effects of chelators in vivo cannot, therefore, be attributed solely to iron chelation.

  20. Metal regeneration of iron chelates in nitric oxide scrubbing

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    Chang, S.G.; Littlejohn, D.; Shi, Y.

    1997-08-19

    The present invention relates to a process of using metal particles to reduce NO to NH{sub 3}. More specifically, the invention concerns an improved process to regenerate iron (II) (CHELATE) by reduction of iron (II) (CHELATE) (NO) complex, which process comprises: (a) contacting an aqueous solution containing iron (II) (CHELATE) (NO) with metal particles at between about 20 and 90 C to reduce NO present, produce ammonia or an ammonium ion, and produce free iron (II) (CHELATE) at a pH of between about 3 and 8. The process is useful to remove NO from flue gas and reduce pollution. 34 figs.

  1. Deferasirox, an oral chelator in the treatment of iron overload

    OpenAIRE

    I. Portioli

    2013-01-01

    BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years o...

  2. A Review on Iron Chelators in Treatment of Iron Overload Syndromes

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    Mobarra, Naser; Shanaki, Mehrnoosh; Ehteram, Hassan; Nasiri, Hajar; Sahmani, Mehdi; Saeidi, Mohsen; Goudarzi, Mehdi; Pourkarim, Hoda; Azad, Mehdi

    2016-01-01

    Iron chelation therapy is used to reduce iron overload development due to its deposition in various organs such as liver and heart after regular transfusion. In this review, different iron chelators implicated in treatment of iron overload in various clinical conditions have been evaluated using more up-to-date studies focusing on these therapeutic agents. Deferoxamine, Deferiprone and Deferasirox are the most important specific US FDA-approved iron chelators. Each of these chelators has their own advantages and disadvantages, various target diseases, levels of deposited iron and clinical symptoms of the afflicted patients which may affect their selection as the best modality. Taken together, in many clinical disorders, choosing a standard chelator does not have an accurate index which requires further clarifications. The aim of this review is to introduce and compare the different iron chelators regarding their advantages and disadvantages, usage dose and specific applications. PMID:27928480

  3. REGIONAL SIDEROSIS: A NEW CHALLENGE FOR IRON CHELATION THERAPY

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    Zvi Ioav Cabantchik

    2013-12-01

    Full Text Available The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a background of normal or subnormal iron levels (e.g. sideroblastic anemias, neuro- and cardio-siderosis in Friedreich ataxia- and neurosiderosis in Parkinson’s disease. We aimed at clearing local siderosis from aberrant labile metal that promotes oxidative damage, without interfering with essential local functions or with hematological iron-associated properties. For this purpose we introduced a conservative mode of iron chelation based on dual activity based on scavenging labile metal but also redeploying it to cell acceptors or to physiological transferrin. The scavenging and redeployment mode of action was designed both for correcting aberrant iron distribution and also for minimizing/preventing systemic loss of chelated metal. We first examine cell models that recapitulate iron maldistribution and associated dysfunctions identified with Friedreich ataxia and Parkinson’s disease and use them to explore the ability of the double-acting agent deferiprone, an orally active chelator, to mediate iron scavenging and redeployment and thereby causing functional improvement. We subsequently evaluate the concept in translational models of disease and finally assess its therapeutic potential in prospective double-blind pilot clinical trials. We claim that any chelator applied to diseases of regional siderosis, cardiac, neuronal or endocrine ought to preserve both systemic and regional iron levels. The proposed deferiprone-based therapy has provided a paradigm for treating regional types of siderosis without affecting hematological parameters and systemic

  4. Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

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    Salehi, Samie; Saljooghi, Amir Sh; Shiri, Ali

    2016-06-15

    Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents.

  5. Hydroxyurea could be a good clinically relevant iron chelator.

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    Khushnooma Italia

    Full Text Available 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 then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  6. Μethods of iron chelation therapy: a bibliographic review

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    Maria Agapiou

    2012-01-01

    Full Text Available "Iron Chelation Therapy" is a term used to describe the procedure of removing excess iron from the body, which is applied after a total of approximately 20 blood transfusions or when serum ferritin levels rise above 1000 ng/ml. Aim: The purpose of the present paper is a retrospective search in bibliography, concerning the methods of iron chelation treatment for patients with hemochromatosis owing to their undergoing multiple blood transfusions. Method: The methology followed, included the search for review and research studies, in electronic databases as well as scientific haematology journals, mostly regarding recent entries in greek and international bibliography. Results: According to the bibliography, chelation therapy compounds have significantly changed the patients' clinical features and have substantially improved their quality of life, along with their outcome over time. However, the level of patient compliance to treatment still remains the basic problem of iron chelation therapy. Conclusions: Even though the discovery of orally administered chelating agents can qualify as an auspicious accomplishment, research fields should cover a much wider spectrum, in order to improve the effectiveness of iron chelation treatment.

  7. Reducing power and iron chelating property of Terminalia chebula (Retz. alleviates iron induced liver toxicity in mice

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    Sarkar Rhitajit

    2012-08-01

    Full Text Available Abstract Background The 70% methanol extract of Terminalia chebula Retz. fruit (TCME was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice. Methods The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound. Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied. Results In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p. caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT, aspartate aminotransferase (ASAT, alkaline phosphatase (ALP and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract

  8. Nanoparticle and iron chelators as a potential novel Alzheimer therapy.

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    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A

    2010-01-01

    Current therapies for Alzheimer disease (AD) such as the acetylcholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of the disease, but do not arrest the disease progression or bring in meaningful remission. New approaches to the disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferrioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. Here, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show unique ability to cross the blood-brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may provide a safer and more effective means of reducing the metal load in neural tissue, thus attenuating the harmful effects of oxidative damage and its sequelae. Experimental procedures are presented in this chapter.

  9. Iron mobilization using chelation and phlebotomy

    DEFF Research Database (Denmark)

    Flaten, T. P.; Aaseth, J.; Andersen, Ole;

    2012-01-01

    Knowledge of the basic mechanisms involved in iron metabolism has increased greatly in recent years, improving our ability to deal with the huge global public health problems of iron deficiency and overload. Several million people worldwide suffer iron overload with serious clinical implications....

  10. Iron chelator daphnetin against Pneumocystis carinii in vitro

    Institute of Scientific and Technical Information of China (English)

    叶彬; 郑玉强; 武卫华; 张静

    2004-01-01

    Background Although there are several drugs and drug combinations for the treatment of Pneumocystis carinii (P. carinii) pneumonia, all drugs have the toxicity as well as low efficacy. Iron chelators have been proposed as a source of new drugs for combating these infections. We hypothesized that iron chelators would suppress the growth of P. carinii by deprivation of the nutritional iron required for growth. In this study, a short-term axenic culture system of P. carinii was established. Daphnetin (7,8-dihydroxycoumarin), a known iron chelator, was demonstrated to exhibit in vitro activity against P. carinii in this system. Methods P. carinii organisms were obtained from the lungs of immunosuppressed rats. The culture system consisted of Iscove Dulbecco Eagle's Minimum Essential Medium (IMDM), supplemented with S-adenosyl-L-methionine, N-acetylglucosamine, putrescine, L-cysteine, L-glutamine, 2-mercaptoethanol, and fetal bovine serum, and was maintained at 37℃, in 5% CO2, 95% O2, at the optimal pH of 8.0. The culture system was used to assess the effect of daphnetin on the proliferation of P. carinii organisms. The ultrastructures of the treated organisms were observed by transmission electron microscopy.Conclusions Daphnetin can suppress the growth of P. carinii in vitro. The efficacy of daphnetin in suppressing the the growth of P. carinii in vitro is related to its ability to chelate iron.

  11. The iron chelator deferasirox protects mice from mucormycosis through iron starvation

    OpenAIRE

    2007-01-01

    Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical...

  12. Neurodegenerative diseases and therapeutic strategies using iron chelators.

    Science.gov (United States)

    Ward, Roberta J; Dexter, David T; Crichton, Robert R

    2015-01-01

    This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed.

  13. Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.

    Science.gov (United States)

    Genc, Gizem Esra; Ozturk, Zeynep; Gumuslu, Saadet; Kupesiz, Alphan

    2016-03-01

    The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.

  14. Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

    Directory of Open Access Journals (Sweden)

    Kwiatkowski JL

    2011-09-01

    Full Text Available Janet L Kwiatkowski The Children's Hospital of Philadelphia, Division of Hematology and University of Pennsylvania School of Medicine, Philadelphia, PA, USA Abstract: Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols. These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading. Keywords: transfusion, iron, chelation, magnetic resonance imaging

  15. Deferasirox, an oral chelator in the treatment of iron overload

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  16. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

    Science.gov (United States)

    Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

    2008-01-01

    Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease.

  17. Antioxidant, Metal Chelating, Anti-glucosidase Activities and Phytochemical Analysis of Selected Tropical Medicinal Plants.

    Science.gov (United States)

    Wong, Fai-Chu; Yong, Ann-Li; Ting, Evon Peir-Shan; Khoo, Sim-Chyi; Ong, Hean-Chooi; Chai, Tsun-Thai

    2014-01-01

    The purpose of this investigation was to determine the antioxidant potentials and anti-glucosidase activities of six tropical medicinal plants. The levels of phenolic constituents in these medicinal plants were also quantified and compared. Antioxidation potentials were determined colorimetrically for scavenging activities against DPPH and NO radicals. Metal chelating assay was based on the measurement of iron-ferrozine absorbance at 562 nm. Anti-diabetic potentials were measured by using α-glucosidase as target enzyme. Medicinal plants' total phenolic, total flavonoid and hydroxycinnamic acid contents were determined using spectrophotometric methods, by comparison to standard plots prepared using gallic acid, quercetin and caffeic acid standards, respectively. Radical scavenging and metal chelating activities were detected in all medicinal plants, in concentration-dependent manners. Among the six plants tested, C. nutans, C. formosana and H. diffusa were found to possess α-glucosidase inhibitory activities. Spectrophotometric analysis indicated that the total phenolic, total flavonoid and hydroxycinnamic acid contents ranged from 12.13-21.39 mg GAE per g of dry sample, 1.83-9.86 mg QE per g of dry sample, and 0.91-2.74 mg CAE per g of dry sample, respectively. Our results suggested that C. nutans and C. formosana could potentially be used for the isolation of potent antioxidants and anti-diabetic compounds. To the best of our knowledge, this study represents the first time that C. nutans (Acanthaceae family) was reported in literature with glucosidase inhibition activity.

  18. The iron chelator deferasirox protects mice from mucormycosis through iron starvation

    Science.gov (United States)

    Clinical and animal model data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the United States (US) Food and Drug Administration (FDA), is a highly effec...

  19. Magnetic memory effect in chelated zero valent iron nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, N., E-mail: nilotpal@vit.ac.in [School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu (India); Mandal, B.K.; Mohan Kumar, K. [School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu (India)

    2012-11-15

    We report the study of nonequilibrium magnetic behavior of air stable zero valent iron nanoparticles synthesized in presence of N-cetyl-N,N,N-trimethyl ammonium bromide chelating agent. X-ray photoelectron spectroscopy study has suggested the presence of iron oxides on nZVI surfaces. Zero-field-cooled and field-cooled magnetization measurements have been carried out at 20-300 K and 100 Oe. For field-cooled measurements with 1 h stops at 200, 100 and 50 K when compared with the warming cycle, we found the signature of magnetic memory effect. A study of magnetic relaxation at the same temperatures shows the existence of two relaxation times. - Highlights: Black-Right-Pointing-Pointer Zero valent iron nanoparticles are synthesized with CTAB chelating agent. Black-Right-Pointing-Pointer X-ray photoelectron spectroscopy study has shown the presence of iron oxide. Black-Right-Pointing-Pointer Magnetization measurement has displayed signature of magnetic memory. Black-Right-Pointing-Pointer Magnetization measurement with time suggested presence of 2 relaxation times.

  20. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

    Directory of Open Access Journals (Sweden)

    Monica Pinheiro de Almeida Verissimo

    2013-01-01

    Full Text Available In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA, presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams and the role of T2* magnetic resonance imaging (MRI to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

  1. Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation.

    Science.gov (United States)

    Minear, Steven; O'Donnell, Allyson F; Ballew, Anna; Giaever, Guri; Nislow, Corey; Stearns, Tim; Cyert, Martha S

    2011-11-01

    Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G(1) phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.

  2. Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous Model Food Systems.

    Science.gov (United States)

    Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2015-09-01

    Many packaged food products undergo quality deterioration due to iron promoted oxidative reactions. Recently, we have developed a nonmigratory iron chelating active packaging material that represents a novel approach to inhibit oxidation of foods while addressing consumer demands for "cleanˮ labels. A challenge to the field of nonmigratory active packaging is ensuring that surface-immobilized active agents retain activity in a true food system despite diffusional limitations. Yet, the relationship between food viscosity and nonmigratory active packaging activity retention has never been characterized. The objective of this study was to investigate the influence of food viscosity on iron chelation by a nonmigratory iron chelating active packaging material. Methyl cellulose was added to aqueous buffered iron solutions to yield model systems with viscosities ranging from ∼1 to ∼10(5)  mPa·s, representing viscosities ranging from beverage to mayonnaise. Iron chelation was quantified by material-bound iron content using colorimetry and inductively coupled plasma-optical emission spectrometry (ICP-OES).  Maximum iron chelation was reached in solutions up to viscosity ∼10(2)  mPa·s. In more viscous solutions (up to ∼10(4)  mPa·s), there was a significant decrease in iron chelating capacity (P influence of different food hydrocolloids on the performance of nonmigratory iron chelating active packaging was characterized. Methyl cellulose and carrageenan did not compete with the material for specific iron chelation (P > 0.05). Materials retained 32% to 45% chelating capacity when in contact with competitively chelating hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates the potential application of nonmigratory iron chelating active packaging in liquid and semi-liquid foods to allow for the removal of synthetic chelators, while maintaining food quality.

  3. Using iron chelating agents to enhance dermatological PDT

    Science.gov (United States)

    Curnow, Alison; Dogra, Yuktee; Winyard, Paul; Campbell, Sandra

    2009-06-01

    Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC however appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and is possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the effect of the novel iron chelator, CP94 on necrotic or apoptotic cell death in cultured human skin fibroblasts and epidermal carcinoma cells incubated with MAL. Furthermore, following a dose escalating safety study conducted with ALA in patients, an additional twelve nodular BCCs were recruited for topical treatment with standard MAL-PDT +/- increasing doses of CP94. Six weeks later following clinical assessment, the whole treatment site was excised for histological analysis. CP94 produced greater cell death in vitro when administered in conjunction with MAL than this porphyrin precursor could produce when administered alone. Clinically, PDT treatment using Metvix + CP94 was a simple and safe modification associated with a trend of reduced tumor thickness with increasing CP94 dose.

  4. Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe(3+)-induced oxidative stress.

    Science.gov (United States)

    Ferlazzo, Nadia; Visalli, Giuseppa; Cirmi, Santa; Lombardo, Giovanni Enrico; Laganà, Pasqualina; Di Pietro, Angela; Navarra, Michele

    2016-04-01

    Exogenous iron in particulate matter and imbalanced iron homeostasis cause deleterious effects on health. Natural and synthetic iron chelators may be of therapeutic benefit, therefore we evaluated the protective effect of Citrus flavonoids-rich extracts from bergamot and orange juices in iron overloaded human lung epithelial cells. Cytofluorimetric, biochemical and genotoxic analyses were performed in Fe2(SO4)3 exposed A549, pretreated with each extract whose chemical composition was previously detected. Chelating activity was assessed in cells by a calcein ester. Both extracts reduced the generation of reactive oxygen species and membrane lipid peroxidation, improved mitochondrial functionality, and prevented DNA-oxidative damage in iron-exposed cells. Antioxidant effects were attributed to the chelating property, blocking upstream the redox activity of iron. Flavonoid-rich extracts also induced antioxidant catalase. The bergamot and orange juice extracts had a broad-spectrum protective effect. Their use prevents iron oxidative injury and these natural iron chelators could be used as therapeutic agents.

  5. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

    Directory of Open Access Journals (Sweden)

    Saliba AN

    2015-06-01

    Full Text Available Antoine N Saliba, Afif R Harb, Ali T Taher Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon Abstract: Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. Keywords: thalassemia, transfusion-dependent thalassemia, iron overload, iron chelation therapy, transfusion

  6. Iron bioavailability in humans from breakfasts enriched with iron bis-glycine chelate, phytates and polyphenols.

    Science.gov (United States)

    Layrisse, M; García-Casal, M N; Solano, L; Barón, M A; Arguello, F; Llovera, D; Ramírez, J; Leets, I; Tropper, E

    2000-09-01

    This study was conducted to determine the bioavailability of iron amino acid chelate (ferrochel) added to fortify breads prepared from either precooked corn flour or white wheat flour + cheese and margarine compared with the same basal breakfast enriched with either ferrous sulfate or iron-EDTA. The inhibitory effect of phytate and polyphenols on iron absorption from ferrochel was also tested. A total of 74 subjects were studied in five experiments. Iron absorption from ferrochel was about twice the absorption from ferrous sulfate (P: American-type coffee did not modify iron absorption significantly, whereas both espresso-type coffee and tea reduced iron absorption from ferrochel by 50% (P: < 0. 05). Ferrochel partially prevented the inhibitory effect of phytates. Because of its high solubility in aqueous solutions even at pH 6, its low interactions with food and high absorption, ferrochel is a suitable compound for food fortification.

  7. Ascorbate status modulates reticuloendothelial iron stores and response to deferasirox iron chelation in ascorbate-deficient rats

    DEFF Research Database (Denmark)

    Brewer, Casey; Otto-Duessel, Maya; Lykkesfeldt, Jens

    2012-01-01

    Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated...... that vitamin C supplementation would improve the availability of transfusional iron to DFX treatment by promoting iron's redox cycling, increasing its soluble ferrous form and promoting its release from reticuloendothelial cells. Osteogenic dystrophy rats (n = 54) were given iron dextran injections for 10...... 12 weeks of sham chelation. Most importantly, ascorbate supplementation at 2250 ppm improved DFX efficiency, allowing DFX to remove 21% more hepatic iron than ascorbate supplementation with 900 ppm or 150 ppm (p vitamin C status modulates the release of iron from...

  8. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  9. Iron chelating active packaging: Influence of competing ions and pH value on effectiveness of soluble and immobilized hydroxamate chelators.

    Science.gov (United States)

    Ogiwara, Yoshiko; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2016-04-01

    Many packaged foods utilize synthetic chelators (e.g. ethylenediaminetetraacetic acid, EDTA) to inhibit iron-promoted oxidation or microbial growth which would result in quality loss. To address consumer demands for all natural products, we have previously developed a non-migratory iron chelating active packaging material by covalent immobilization of polyhydroxamate and demonstrated its efficacy in delaying lipid oxidation. Herein, we demonstrate the ability of this hydroxamate-functionalized iron chelating active packaging to retain iron chelating capacity; even in the presence of competing ions common in food. Both immobilized and soluble hydroxamate chelators retained iron chelating capacity in the presence of calcium, magnesium, and sodium competing ions, although at pH 5.0 the presence of calcium reduced immobilized hydroxamate iron chelation. A strong correlation was found between colorimetric and mass spectral analysis of iron chelation by the chelating packaging material. Such chelating active packaging may support reducing additive use in product formulations, while retaining quality and shelf life.

  10. Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.

    Directory of Open Access Journals (Sweden)

    Jasmine L Hamilton

    Full Text Available Iron chelation therapy using iron (III specific chelators such as desferrioxamine (DFO, Desferal, deferasirox (Exjade or ICL-670, and deferiprone (Ferriprox or L1 are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity.

  11. Generation, Fractionation, and Characterization of Iron-Chelating Protein Hydrolysate from Palm Kernel Cake Proteins.

    Science.gov (United States)

    Zarei, Mohammad; Ghanbari, Rahele; Tajabadi, Naser; Abdul-Hamid, Azizah; Bakar, Fatimah Abu; Saari, Nazamid

    2016-02-01

    Palm kernel cake protein was hydrolyzed with different proteases namely papain, bromelain, subtilisin, flavourzyme, trypsin, chymotrypsin, and pepsin to generate different protein hydrolysates. Peptide content and iron-chelating activity of each hydrolysate were evaluated using O-phthaldialdehyde-based spectrophotometric method and ferrozine-based colorimetric assay, respectively. The results revealed a positive correlation between peptide contents and iron-chelating activities of the protein hydrolysates. Protein hydrolysate generated by papain exhibited the highest peptide content of 10.5 mM and highest iron-chelating activity of 64.8% compared with the other hydrolysates. Profiling of the papain-generated hydrolysate by reverse phase high performance liquid chromatography fractionation indicated a direct association between peptide content and iron-chelating activity in most of the fractions. Further fractionation using isoelectric focusing also revealed that protein hydrolysate with basic and neutral isoelectric point (pI) had the highest iron-chelating activity, although a few fractions in the acidic range also exhibited good metal chelating potential. After identification and synthesis of papain-generated peptides, GGIF and YLLLK showed among the highest iron-chelating activities of 56% and 53%, whereas their IC50 were 1.4 and 0.2 μM, respectively.

  12. Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation--A Chemical Approach.

    Directory of Open Access Journals (Sweden)

    Thiago C Genaro-Mattos

    Full Text Available Caffeic acid (CA is a phenolic compound widely found in coffee beans with known beneficial effects in vivo. Many studies showed that CA has anti-inflammatory, anti-mutagenic, antibacterial and anti-carcinogenic properties, which could be linked to its antioxidant activity. Taking in consideration the reported in vitro antioxidant mechanism of other polyphenols, our working hypothesis was that the CA antioxidant activity could be related to its metal-chelating property. With that in mind, we sought to investigate the chemical antioxidant mechanism of CA against in vitro iron-induced oxidative damage under different assay conditions. CA was able to prevent hydroxyl radical formation promoted by the classical Fenton reaction, as determined by 2-deoxyribose (2-DR oxidative degradation and DMPO hydroxylation. In addition to its ability to prevent hydroxyl radical formation, CA had a great inhibition of membrane lipid peroxidation. In the lipid peroxidation assays CA acted as both metal-chelator and as hydrogen donor, preventing the deleterious action promoted by lipid-derived peroxyl and alkoxyl radicals. Our results indicate that the observed antioxidant effects were mostly due to the formation of iron-CA complexes, which are able to prevent 2-DR oxidation and DMPO hydroxylation. Noteworthy, the formation of iron-CA complexes and prevention of oxidative damage was directly related to the pH of the medium, showing better antioxidant activity at higher pH values. Moreover, in the presence of lipid membranes the antioxidant potency of CA was much higher, indicating its enhanced effectiveness in a hydrophobic environment. Overall, our results show that CA acts as an antioxidant through an iron chelating mechanism, preventing the formation of free hydroxyl radicals and, therefore, inhibiting Fenton-induced oxidative damage. The chemical properties of CA described here--in association with its reported signaling effects--could be an explanation to its

  13. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

    Science.gov (United States)

    Ceci, Adriana; Mangiarini, Laura; Felisi, Mariagrazia; Bartoloni, Franco; Ciancio, Angela; Capra, Marcello; D'Ascola, Domenico; Cianciulli, Paolo; Filosa, Aldo

    2011-01-01

    Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups. PMID:21738864

  14. The Management of Iron Chelation Therapy: Preliminary Data from a National Registry of Thalassaemic Patients

    Directory of Open Access Journals (Sweden)

    Adriana Ceci

    2011-01-01

    Full Text Available Thalassaemia and other haemoglobinopathies constitute an important health problem in Mediterranean countries, placing a tremendous emotional, psychological, and economic burden on their National Health systems. The development of new chelators in the most recent years had a major impact on the treatment of thalassaemia and on the quality of life of thalassaemic patients. A new initiative was promoted by the Italian Ministry of Health, establishing a Registry for thalassaemic patients to serve as a tool for the development of cost-effective diagnostic and therapeutic approaches and for the definition of guidelines supporting the most appropriate management of the iron-chelating therapy and a correct use of the available iron-chelating agents. This study represents the analysis of the preliminary data collected for the evaluation of current status of the iron chelation practice in the Italian thalassaemic population and describes how therapeutic interventions can widely differ in the different patients' age groups.

  15. Randomised controlled trials of iron chelators for the treatment of cardiac siderosis in thalassaemia major

    Directory of Open Access Journals (Sweden)

    Arun John Baksi

    2014-09-01

    Full Text Available In conditions requiring repeated blood transfusion or where iron metabolism is abnormal, heart failure may result from accumulation of iron in the heart (cardiac siderosis. Death due to heart failure from cardiac iron overload has accounted for considerable early mortality in β-thalassemia major. The ability to detect iron loading in the heart by cardiovascular magnetic resonance using T2* sequences has created an opportunity to intervene in the natural history of such conditions. However, effective and well tolerated therapy is required to remove iron from the heart. There are currently 3 approved commercially available iron chelators: deferoxamine, deferiprone and deferasirox. We review the high quality randomised controlled trials in this area for iron chelation therapy in the management of cardiac siderosis.

  16. Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.

    NARCIS (Netherlands)

    Bartels-Stringer, M.; Wetzels, J.F.M.; Wouterse, A.C.; Steenbergen, E.; Russel, F.G.M.; Kramers, C.

    2005-01-01

    BACKGROUND: In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused

  17. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Jun-Peng Guo

    Full Text Available Patients of Alzheimer's disease (AD frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe, displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ, increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO, another iron chelator, selectively inhibited osteoclast (OC differentiation, without an obvious effect on osteoblast (OB differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  18. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Guo, Jun-Peng; Pan, Jin-Xiu; Xiong, Lei; Xia, Wen-Fang; Cui, Shun; Xiong, Wen-Cheng

    2015-01-01

    Patients of Alzheimer's disease (AD) frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe), displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ), increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT) mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO), another iron chelator, selectively inhibited osteoclast (OC) differentiation, without an obvious effect on osteoblast (OB) differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs) from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  19. Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators

    Science.gov (United States)

    Akam, Eman A.; Chang, Tsuhen M.; Astashkin, Andrei V.

    2014-01-01

    Iron scavengers (chelators) offer therapeutic opportunities in anticancer drug design by targeting the increased demand for iron in cancer cells as compared to normal cells. Prochelation approaches are expected to avoid systemic iron depletion as chelators are liberated under specific intracellular conditions. In the strategy described herein, a disulfide linkage is employed as a redox-directed switch within the binding unit of an antiproliferative thiosemicarbazone prochelator, which is activated for iron coordination following reduction to the thiolate chelator. In glutathione redox buffer, this reduction event occurs at physiological concentrations and half-cell potentials. Consistent with concurrent reduction and activation, higher intracellular thiol concentrations increase cell susceptibility to prochelator toxicity in cultured cancer cells. The reduction of the disulfide switch and intracellular iron chelation are confirmed in cell-based assays using calcein as a fluorescent probe for paramagnetic ions. The resulting low-spin Fe(III) complex is identified in intact Jurkat cells by EPR spectroscopy measurements, which also document a decreased concentration of active ribonucleotide reductase following exposure to the prochelator. Cell viability and fluorescence-based assays show that the iron complex presents low cytotoxicity and does not participate in intracellular redox chemistry, indicating that this antiproliferative chelation strategy does not rely on the generation of reactive oxygen species. PMID:25100578

  20. Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation

    Institute of Scientific and Technical Information of China (English)

    WANG Lu; YAN WenChao; CHEN JiaChuan; HUANG Feng; GAO PeiJi

    2008-01-01

    An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator,oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the β-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more accessible to degradation.

  1. Function of the iron-binding chelator produced by Coriolus versicolor in lignin biodegradation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An ultrafiltered low-molecular-weight preparation of chelating compounds was isolated from a wood-containing culture of the white-rot basidiomycete Coriolus versicolor. This preparation could chelate Fe3+ and reduce Fe3+ to Fe2+, demonstrating that the substance may serve as a ferric chelator, oxygen-reducing agent, and redox-cycling molecule, which would include functioning as the electron transport carrier in Fenton reaction. Lignin was treated with the iron-binding chelator and the changes in structure were investigated by 1H-NMR, 13C-NMR, difference spectrum caused by ionization under alkaline conditions and nitrobenzene oxidation. The results indicated that the iron-binding chelator could destroy the β-O-4 bonds in etherified lignin units and insert phenolic hydroxyl groups. The low-molecular-weight chelator secreted by C. versicolor resulted in new phenolic substructures in the lignin polymer, making it susceptible to attack by laccase or manganese peroxidase. Thus, the synergic action of the iron-binding chelator and the lignocellulolytic enzymes made the substrate more acces- sible to degradation.

  2. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    OpenAIRE

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2011-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine...

  3. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2015-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults. Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators. PMID:21523808

  4. Iron chelation adherence to deferoxamine and deferasirox in thalassemia.

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A; Porter, John; Coates, Thomas; Giardina, Patricia J; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J

    2011-05-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators.

  5. Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

    Directory of Open Access Journals (Sweden)

    Mona Mosayebnia

    2014-01-01

    Full Text Available Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. Materials and Methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2 cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO, a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay as well. Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems. Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage.

  6. Iron reverses impermeable chelator inhibition of DNA synthesis in CCl 39 cells.

    OpenAIRE

    Alcain, F J; Löw, H; Crane, F. L.

    1994-01-01

    Treatment of Chinese hamster lung fibroblasts (CCl 39 cells) with the impermeable iron(II) chelator bathophenanthroline disulfonate (BPS) inhibits DNA synthesis when cell growth is initiated with growth factors including epidermal growth factor plus insulin, thrombin, or ceruloplasmin, but not with 10% fetal calf serum. The BPS treatment inhibits transplasma membrane electron transport. The treatment leads to release of iron from the cells as determined by BPS iron(II) complex formation over ...

  7. Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

    Science.gov (United States)

    Flora, S J S; Bhadauria, Smrati; Kannan, G M; Singh, Nutan

    2007-04-01

    Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

  8. The Effect of Chelating Copolymer Additive on the Yttrium Iron Garnet Nanoparticle Formation

    Institute of Scientific and Technical Information of China (English)

    Wang; Cheng-chien

    2007-01-01

    1 Results Yttrium iron garnet (YIG) is a well-known ferromagnetic garnet material and has widely used in electronic devices[1].A new acrylic chelating polymer was developed to act as the additive of the preparation of YIG precursor in our previous study[2].The sintering temperature of YIG nanocrystal obtained by this YIG precursor (ACP) was magnificently descended from 1 000 to 600 ℃.In this study,we were further to study the effect of amount of chelating polymer and the compositions of chelating polyme...

  9. Targeted Iron Chelation Will Improve Recovery after Spinal Cord Injury

    Science.gov (United States)

    2014-10-01

    spinal cord injury there is limited improvement in locomotor function and increased spared of grey matter . Since iron accumulation occurs in a protracted...sparing, progenitor cell proliferation, oligodendrocyte genesis, neurons ( grey matter ), apoptosis, iron (months 3) We completed the...immunohistochemistry for white and grey matter tissue sparing, macrophage induced inflammation, oligodendrocyte genesis, iron accumulation, and neuron sparing. All

  10. Toxicity of chelated iron (Fe-DTPA) in American cranberry

    Science.gov (United States)

    American cranberry (Vaccinium macrocarpon) is naturally adapted to environments with high concentrations of soluble iron. Yet, there is a need to further explore iron nutrition in cranberry given concerns of toxicity problems from irrigation with iron-rich water. This study investigated the threat o...

  11. DCCP and DICP: Construction and Analyses of Databases for Copper- and Iron-Chelating Proteins

    Institute of Scientific and Technical Information of China (English)

    Hao Wu; Yan Yang; Sheng-Juan Jiang; Ling-Ling Chen; Hai-Xia Gao; Qing-Shan Fu; Feng Li; Bin-Guang Ma; Hong-Yu Zhang

    2005-01-01

    Copper and iron play important roles in a variety of biological processes, especially when being chelated with proteins. The proteins involved in the metal binding,transporting and metabolism have aroused much interest. To facilitate the study on this topic, we constructed two databases (DCCP and DICP) containing the known copper- and iron-chelating proteins, which are freely available from the website http:∥sdbi.sdut.edu.cn/en. Users can conveniently search and browse all of the entries in the databases. Based on the two databases, bioinformatic analyses were performed, which provided some novel insights into metalloproteins.

  12. [Iron chelate treatment of hereditary sideroblastic anemia complicated by hemochromatosis].

    Science.gov (United States)

    Kremp, L; Girot, R; Alliot, S; Najean, Y; Douchain, F; Hongre, J F

    1983-01-01

    In a child with sideroblastic anemia complicated with hemochromatosis, iron overload was successfully treated with slow subcutaneous perfusion of deferoxamine. A 28 month-treatment resulted in the inversion of iron balance, which became negative, and the normalization of serum ferritin and abdominal CT scan. These results indicate that deferoxamine perfusion 12/24 hrs is able to restrict or even to remove the iron overload, previously responsible for hemochromatosis, a factor of mortality in this disease.

  13. Mössbauer spectroscopic study of iron-chelate trammels

    Science.gov (United States)

    Pal, Sangita; Meena, S. S.; Ningthoujam, R. S.; Goswami, D.

    2014-04-01

    Any kind of waste effluent in the Indian context and other countries contains a lot of iron in any ore. During mining, milling, extraction and purification process iron acts as contaminant towards other metal's purity. It is essential to remove iron to the maximum extent. In this case, an "IN-HOUSE" resin polyacrylamidehydroxamic acid (PHOA) has been designed and developed which is highly hydrophilic three dimensionally cross-linked. It has an excellent iron binding capacity with almost no leaching. Interaction of resin with ammonium ferrous sulphate and red-mod (Fe2O3) is studied using Mössbauer spectroscopy.

  14. Chapter 5 - Development of iron chelator-nanoparticle conjugates as potential therapeutic agents for Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A

    2009-01-01

    Oxidative stress is known to play a key role in the initiation and promotion of the neurodegeneration that characterizes the pathogenesis of Alzheimer disease (AD). An accumulation of redox active transition metals, including iron and copper, is likely a major generator of reactive oxidative species and other free radicals and is thought to induce a detrimental cycle of oxidative stress, amyloid-beta aggregation, and neurodegeneration. As such, metal chelators may provide an alternative therapeutic approach to sequester redox active metals and prevent the onslaught of oxidative damage. Unfortunately, however, metal chelation approaches are currently limited in their potential, since many cannot readily pass the blood-brain barrier (BBB), due to their hydrophilicity, and many are neurotoxic at high concentrations. To circumvent such issues, here we describe the development of iron chelator-nanoparticle conjugation that allows delivery of target chelator to the brain in the absence of neurotoxicity. Such nanoparticle delivery of iron chelators will likely provide a highly advantageous mode of attack on the oxidative stress that plagues AD as well as other conditions characterized by excess metal accumulation.

  15. Yerba mate (Ilex paraguariensis St. Hill.)-based beverages: How successive extraction influences the extract composition and its capacity to chelate iron and scavenge free radicals.

    Science.gov (United States)

    Colpo, Ana C; Rosa, Hemerson; Lima, Maria Eduarda; Pazzini, Camila Eliza F; de Camargo, Vanessa B; Bassante, Felipa E M; Puntel, Robson; Ávila, Daiana Silva; Mendez, Andreas; Folmer, Vanderlei

    2016-10-15

    Chimarrão or mate is a popular beverage from South America that is drank with successive infusions. Although yerba mate extracts have been widely studied, few studies have described the extract contents in beverages. Using yerba mate samples from Brazil, Argentina, and Uruguay, we examined the extract chromatographic profiles, total polyphenol content and their capacities to chelate iron. In addition, we analyzed antioxidant activity by examining the ability of the extracts to scavenge DPPH and NO. Our results showed that the amount of extracted compound was highest in yerba mate extract from Uruguay, followed by Argentina, then Brazil. Herbs from all three areas had a significant capacity to inhibit DPPH and NO free radicals. The Brazilian and Uruguayan herbs had an 80% iron chelation capacity (p<0.001), while the iron chelation capacity of the Argentinean herb was lower but still significant (p⩽0.05). We conclude that the compound concentration decreases with successive extractions, while the antioxidant capacity is maintained at significant levels.

  16. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

    Directory of Open Access Journals (Sweden)

    Kell Douglas B

    2009-01-01

    Full Text Available Abstract Background The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. Review We review the considerable and wide-ranging evidence for the involvement of this combination of (superoxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation. The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, since in some circumstances (especially the presence of poorly liganded iron molecules that are nominally antioxidants can actually act as pro

  17. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation

    Science.gov (United States)

    Yang, Chunguang; Ma, Xueyou; Wang, Zhihua; Zeng, Xing; Hu, Zhiquan; Ye, Zhangqun; Shen, Guanxin

    2017-01-01

    Background Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties. Materials and methods CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot. Results Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin. Conclusion Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties. PMID:28243065

  18. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis

    Science.gov (United States)

    Ibrahim, Ashraf S.; Gebremariam, Teclegiorgis; French, Samuel W.; Edwards, John E.; Spellberg, Brad

    2010-01-01

    Objectives Increased bone marrow iron levels in patients with haematological malignancies is an independent risk factor for developing invasive pulmonary aspergillosis (IPA), suggesting an important role for iron uptake in the pathogenesis of IPA. We sought to determine the potential for combination therapy with the iron chelator deferasirox + liposomal amphotericin B (LAmB) to improve the outcome of murine IPA compared with LAmB monotherapy. Methods In vitro MIC and minimum fungicidal concentration (MFC) values of the iron chelator, deferasirox, for Aspergillus fumigatus were determined by microdilution assay. In addition, we studied the efficacy of deferasirox alone or combined with LAmB in treating immunocompromised mice infected with A. fumigatus via inhalation. Results Deferasirox was cidal in vitro against A. fumigatus, with an MIC and MFC of 25 and 50 mg/L, respectively. Deferasirox monotherapy modestly prolonged survival of mice with IPA. Combination deferasirox + LAmB therapy synergistically improved survival and reduced lung fungal burden compared with either monotherapy alone. Conclusions Iron chelation therapy with deferasirox alone or in combination with LAmB is effective in treating experimental IPA. Further study of deferasirox is warranted as adjunctive therapy for IPA infections. PMID:19942619

  19. Is aceruloplasminemia treatable? Combining iron chelation and fresh-frozen plasma treatment.

    Science.gov (United States)

    Poli, L; Alberici, A; Buzzi, P; Marchina, E; Lanari, A; Arosio, C; Ciccone, A; Semeraro, F; Gasparotti, R; Padovani, A; Borroni, Barbara

    2017-02-01

    We report the case of a patient with hereditary ceruloplasmin deficiency due to a novel gene mutation in ceruloplasmin gene (CP), treated with fresh frozen plasma (FFP) and iron chelation therapy. A 59-year-old man with a past history of diabetes was admitted to our department due to progressive gait difficulties and cognitive impairment. Neurological examination revealed a moderate cognitive decline, with mild extrapyramidal symptoms, ataxia, and myoclonus. Brain T2-weighted MR imaging showed bilateral basal ganglia hypointensity with diffuse iron deposition. Increased serum ferritin, low serum copper concentration, undetectable ceruloplasmin, and normal urinary copper excretion were found. The genetic analysis of the CP (OMIM #604290) reported compound heterozygosity for two mutations, namely c.848G > A and c.2689_2690delCT. Treatment with FFP (500 mL i.v./once a week) and administration of iron chelator (Deferoxamine 1000 mg i.v/die for 5 days, followed by Deferiprone 500 mg/die per os) were undertaken. At the 6-month follow-up, clinical improvement of gait instability, trunk ataxia, and myoclonus was observed; brain MRI scan showed no further progression of basal ganglia T2 hypointensity. This case report suggests that the early initiation of combined treatment with FFP and iron chelation may be useful to reduce the accumulation of iron in the central nervous system and to improve the neurological symptoms.

  20. The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial

    NARCIS (Netherlands)

    Eijk, L.T.G.J. van; Heemskerk, S.; Pluijm, R.W. van der; Wijk, S.M. van; Peters, W.H.M.; Hoeven, J.G. van der; Kox, M.; Swinkels, D.W.; Pickkers, P.

    2014-01-01

    In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate i

  1. Nanoparticle iron chelators: a new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Harris, Peggy L R; Rolston, Raj K; Perry, George; Smith, Mark A

    2006-10-09

    Accumulating evidence suggests that oxidative stress may be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer disease. Contributing to this, there is a dyshomeostasis of metal ions in Alzheimer disease with abnormally high levels of redox-active metals, particularly iron, in affected areas of the brain. Although it is unclear whether metal excesses are the sole cause of oxidative stress and neurodegeneration or a by-product of neuronal loss, the finding that metal chelators can partially solubilize amyloid-beta deposits in Alzheimer disease suggests a promising therapeutic role for chelating agents. However, the blood-brain barrier and toxicity of known chelators limit their utility. In this study, we suggest that covalent conjugation of iron chelators with nanoparticles may help overcome the limitations in blood-brain barrier permeability of existing chelation therapy. Using in vitro studies, we have shown that a chelator-nanoparticle system and the chelator-nanoparticle system complexed with iron, when incubated with human plasma, preferentially adsorb apolipoprotein E and apolipoprotein A-I, that would facilitate transport into and out of the brain via mechanisms used for transporting low-density lipoprotein. Our studies suggest a unique approach, utilizing nanoparticles, to transport chelators and chelator-metal complexes in both directions across the blood-brain barrier, thus providing safer and more effective chelation treatment in Alzheimer disease and other neurodegenerative diseases.

  2. Comparison of antioxidative and chelating effects of daidzein and daidzin on protein oxidative modification by copper in vitro.

    Science.gov (United States)

    Toda, S; Shirataki, Y

    2001-01-01

    Daidzein and its glycoside daidzin are isoflavones. Their antioxidative effects were compared in vitro. Although both compounds inhibited protein oxidative modification by copper, the inhibitory effect of daidzein was stronger than that of daidzin. Because daidzein showed a greater affinity for Cu2+, the antioxidant effect of these isoflavones may be dependent on their respective copper-chelating abilities.

  3. Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety as novel pluripotential therapeutic agents for Alzheimer's disease: a tribute to Moussa Youdim.

    Science.gov (United States)

    Weinreb, Orly; Mandel, Silvia; Bar-Am, Orit; Amit, Tamar

    2011-03-01

    It is for these authors a great privilege to dedicate this review article to Moussa Youdim, who is one of the most imperative pharmacologists and pioneer investigators in the search and development of novel therapeutics for neurodegenerative diseases. 40 years ago, Moussa Youdim has started studying brain iron, catecholamine receptor and monoamine oxidase (MAO)-A and -B functions. Although Moussa Youdim succeeded in exploring the novel anti-Parkinsonian, selective MAO-B inhibitor drug, rasagiline (Azilect, Teva Pharmaceutical Co.), he did not stop searching for superior therapeutic approaches for neurodegenerative disorders. To date, Moussa Youdim and his research group are designing and synthesizing pluripotential drug candidates possessing diverse pharmacological properties that can act on multiple targets and pathological features ascribed to Parkinson's disease, Alzheimer's disease (AD) and amyotrophic lateral sclerosis. One such example is the multimodal non-toxic, brain-permeable iron-chelating compound, M30 (5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline), which amalgamates the propargyl moiety of rasagiline with the backbone of the potent iron chelator, VK28. This review discusses the multiple effects of several leading compounds of this series, concerning their neuroprotective/neurorestorative molecular mechanisms in vivo and in vitro, with a special focus on the pathological features ascribed to AD, including antioxidant and iron chelating activities, regulation of amyloid precursor protein and amyloid β peptide expression processing, activation of pro-survival signaling pathways and regulation of cell cycle and neurite outgrowth.

  4. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    Energy Technology Data Exchange (ETDEWEB)

    Berko, A; Schofield, E J; Chadwick, A V [School of Physical Sciences, University of Kent, CT2 7NR (United Kingdom); Smith, A D [STFC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Jones, A M [The Mary Rose Trust, HM Naval Base, Portsmouth, PO1 3LX (United Kingdom); Mosselmans, J F W, E-mail: a.berko@kent.ac.u [Diamond Light Source, Didcot, OX11 0DE (United Kingdom)

    2009-11-15

    The oxidation of sulfur in marine archaeological timbers under museum storage conditions is a recently identified problem, particularly for major artefacts such as historic ships excavated from the seabed. Recent work on the Vasa has stressed the role of iron in catalysing the oxidative degradation of the wood cellulose and the polyethylene glycols used to restore mechanical integrity to the timbers. In developing new treatment protocols for the long term preservation of Henry VIII of England's flagship, the Mary Rose, we are investigating the potential of chelating agents to neutralise and remove the iron products from the ships timbers. We have explored the use of aqueous solutions of chelating agents of calcium phytate, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ammonium citrate to extract the iron compounds. All of these solutions exhibit some level of iron removal; however the key is to find the most effective concentration at pH of around 7 of the reagent solution, to minimise the treatment time and find the most cost-effective treatment for the whole of the Mary Rose hull. Fe K-edge XAFS data from samples of Mary Rose timbers, before and after treatment by the chelating agents mentioned has been collected. The data collected provide valuable insights into the effectiveness of the treatment solutions.

  5. XAS studies of the effectiveness of iron chelating treatments of Mary Rose timbers

    Science.gov (United States)

    Berko, A.; Smith, A. D.; Jones, A. M.; Schofield, E. J.; Mosselmans, J. F. W.; Chadwick, A. V.

    2009-11-01

    The oxidation of sulfur in marine archaeological timbers under museum storage conditions is a recently identified problem, particularly for major artefacts such as historic ships excavated from the seabed. Recent work on the Vasa has stressed the role of iron in catalysing the oxidative degradation of the wood cellulose and the polyethylene glycols used to restore mechanical integrity to the timbers. In developing new treatment protocols for the long term preservation of Henry VIII of England's flagship, the Mary Rose, we are investigating the potential of chelating agents to neutralise and remove the iron products from the ships timbers. We have explored the use of aqueous solutions of chelating agents of calcium phytate, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) and ammonium citrate to extract the iron compounds. All of these solutions exhibit some level of iron removal; however the key is to find the most effective concentration at pH of around 7 of the reagent solution, to minimise the treatment time and find the most cost-effective treatment for the whole of the Mary Rose hull. Fe K-edge XAFS data from samples of Mary Rose timbers, before and after treatment by the chelating agents mentioned has been collected. The data collected provide valuable insights into the effectiveness of the treatment solutions.

  6. Effects of oral iron chelator deferasirox on human malignant lymphoma cells

    Science.gov (United States)

    Choi, Jong Gwon; Kim, Jung-Lim; Park, Joohee; Lee, Soonwook; Park, Seh Jong; Kim, Jun Suk

    2012-01-01

    Background Iron is essential for cell proliferation and viability. It has been reported that iron depletion by a chelator inhibits proliferation of some cancer cells. Deferasirox is a new oral iron chelator, and a few reports have described its effects on lymphoma cells. The goal of this study was to determine the anticancer effects of deferasirox in malignant lymphoma cell lines. Methods Three human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) were treated with deferasirox at final concentrations of 20, 50, or 100 µM. Cell proliferation was evaluated by an MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry. Western blot analysis was performed to determine the relative activity of various apoptotic pathways. The role of caspase in deferasirox-induced apoptosis was investigated using a luminescent assay. Results The MTT assay showed that deferasirox had dose-dependent cytotoxic effects on all 3 cell lines. Cell cycle analysis showed that the sub-G1 portion increased in all 3 cell lines as the concentration of deferasirox increased. Early apoptosis was also confirmed in the treated cells by Annexin V and PI staining. Western blotting showed an increase in the cleavage of PARP, caspase 3/7, and caspase 9 in deferasirox-treated groups. Conclusion We demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspase-9 pathway. PMID:23071474

  7. Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent

    OpenAIRE

    Ji Won Lee; Hyoung Jin Kang; Ji-Yeob Choi; Nam Hee Kim; Mi Kyung Jang; Chang-Woo Yeo; Sang Seop Lee; Hyery Kim; June Dong Park; Kyung Duk Park; Hee Young Shin; Jae-Gook Shin; Hyo Seop Ahn

    2013-01-01

    Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-asso...

  8. Selection of Chelated Fe (III)/Fe (II) Catalytic Oxidation Agents for Desulfurization Based on Iron Complexation Method

    Institute of Scientific and Technical Information of China (English)

    Luo Ying; Liu Youzhi; Qi Guisheng; Guo Huidong; Zhu Zhengfeng

    2014-01-01

    Optimization of factors inlfuencing the experiments on reactions involving 8 different chelating agents and sol-uble Fe (III)/Fe (II) salts was carried out to yield chelated iron complexes. A combination of optimized inlfuencing factors has resulted in a Fe chelating capacity of the iron-based desulfurization solution to be equal to 6.83-13.56 g/L at a redox potential of 0.185-0.3. The desulfurization performance of Fe (III)/Fe (II) chelating agents was investigated on a simulated sulfur-containing industrial gas composed of H2S and N2 in a cross-lfow rotating packed bed. Test results have revealed that the proposed iron-based desulfurization solution showed a sulfur removal efifciency of over 99%along with a Fe chelating capacity exceeding 1.35 g/L. This desulfurization technology which has practical application prospect is currently in the phase of commercial scale-up study.

  9. Extraction of Micronutrient Metals from Peat-based Media Using Various Chelate-ligand and Iron-source Extractants

    Science.gov (United States)

    Objectives of the study were to determine effects of chelate-ligand (experiment 1) and iron-source (experiment 2) unbuffrered extractant solutions on substrate pH and Cu, Fe, Mn, and Zn extraction from peat-based media. Chelate-ligand extractants consisted of 5 mM solutions of ethylenediaminedisucc...

  10. Regulation of quinolinic acid neosynthesis in mouse, rat and human brain by iron and iron chelators in vitro.

    Science.gov (United States)

    Stachowski, Erin K; Schwarcz, Robert

    2012-02-01

    Several lines of evidence indicate that excess iron may play an etiologically significant role in neurodegenerative disorders. This idea is supported, for example, by experimental studies in animals demonstrating significant neuroprotection by iron chelation. Here, we tested whether this effect might be related to a functional link between iron and the endogenous excitotoxin quinolinic acid (QUIN), a presumed pathogen in several neurological disorders. In particular, the present in vitro study was designed to examine the effects of Fe(2+), a known co-factor of oxygenases, on the activity of QUIN's immediate biosynthetic enzyme, 3-hydroxyanthranilic acid dioxygenase (3HAO), in the brain. In crude tissue homogenate, addition of Fe(2+) (2-40 μM) stimulated 3HAO activity 4- to 6-fold in all three species tested (mouse, rat and human). The slope of the iron curve was steepest in rat brain where an increase from 6 to 14 μM resulted in a more than fivefold higher enzyme activity. In all species, the Fe(2+)-induced increase in 3HAO activity was dose-dependently attenuated by the addition of ferritin, the main iron storage protein in the brain. The effect of iron was also readily prevented by N,N'-bis(2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), a synthetic iron chelator with neuroprotective properties in vivo. All these effects were reproduced using neostriatal tissue obtained postmortem from normal individuals and patients with end-stage Huntington's disease. Our results suggest that QUIN levels and function in the mammalian brain might be tightly controlled by endogenous iron and proteins that regulate the bioavailability of iron.

  11. The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

    Directory of Open Access Journals (Sweden)

    Berdoussi Eleni

    2009-06-01

    Full Text Available Abstract Background Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR. Results For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis" assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline. Conclusion With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.

  12. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    OpenAIRE

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, def...

  13. Factors Influencing the DNA Nuclease Activity of Iron, Cobalt, Nickel, and Copper Chelates

    OpenAIRE

    Joyner, Jeff C.; Reichfield, Jared; Cowan, J.A.

    2011-01-01

    A library of complexes that included iron, cobalt, nickel, and copper chelates of cyclam, cyclen, DOTA, DTPA, EDTA, tripeptide GGH, tetrapeptide KGHK, NTA, and TACN was evaluated for DNA nuclease activity, ascorbate consumption, superoxide and hydroxyl radical generation, and reduction potential under physiologically relevant conditions. Plasmid DNA cleavage rates demonstrated by combinations of each complex and biological coreactants were quantified by gel electrophoresis, yielding second-or...

  14. Iron Chelation Therapy with Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

    Science.gov (United States)

    Elli, Elena Maria; Belotti, Angelo; Aroldi, Andrea; Parma, Matteo; Pioltelli, Pietro; Pogliani, Enrico Maria

    2014-01-01

    Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required. PMID:24959339

  15. IRON CHELATION THERAPY WITH DEFERASIROX IN THE MANAGEMENT OF IRON OVERLOAD IN PRIMARY MYELOFIBROSIS

    Directory of Open Access Journals (Sweden)

    Elena Maria Elli

    2014-05-01

    Full Text Available Deferasirox (DSX is the principal option currently available for iron-chelation-therapy (ICT, principally in the management of myelodysplastic syndromes (MDS, while in primary myelofibrosis (PMF the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day, with 3 transient interruption of treatment for drug-related adverse events (AEs and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%, 2 of them (20% obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin were greater in hematologic responder (HR compared with non-responder (NR  patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP. Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP.  However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

  16. CIPK23 is involved in iron acquisition of Arabidopsis by affecting ferric chelate reductase activity.

    Science.gov (United States)

    Tian, Qiuying; Zhang, Xinxin; Yang, An; Wang, Tianzuo; Zhang, Wen-Hao

    2016-05-01

    Iron deficiency is one of the major limiting factors affecting quality and production of crops in calcareous soils. Numerous signaling molecules and transcription factors have been demonstrated to play a regulatory role in adaptation of plants to iron deficiency. However, the mechanisms underlying the iron deficiency-induced physiological processes remain to be fully dissected. Here, we demonstrated that the protein kinase CIPK23 was involved in iron acquisition. Lesion of CIPK23 rendered Arabidopsis mutants hypersensitive to iron deficiency, as evidenced by stronger chlorosis in young leaves and lower iron concentration than wild-type plants under iron-deficient conditions by down-regulating ferric chelate reductase activity. We found that iron deficiency evoked an increase in cytosolic Ca(2+) concentration and the elevated Ca(2+) would bind to CBL1/CBL9, leading to activation of CIPK23. These novel findings highlight the involvement of calcium-dependent CBL-CIPK23 complexes in the regulation of iron acquisition. Moreover, mutation of CIPK23 led to changes in contents of mineral elements, suggesting that CBL-CIPK23 complexes could be as "nutritional sensors" to sense and regulate the mineral homeostasis in Arabisopsis.

  17. Effect of biodegradable chelating ligand on iron bioavailability and radish growth

    OpenAIRE

    2010-01-01

    The effect of chelating ligands on iron (Fe) uptake and growth of radish (Raphanus sativus L.) was investigated. The ethylenediaminetetraacetic acid (EDTA) increased 55Fe uptake in roots of radish though its subsequent translocation from roots to shoots and leaves did not increase. About 70%-80% of the total 55Fe was distributed in the roots while about 5%-15% and 11%-17% were in shoots and leaves, respectively. The EDTA increased iron uptake into the roots of radish, but not in the above gro...

  18. Pharmacogenetic study of deferasirox, an iron chelating agent.

    Directory of Open Access Journals (Sweden)

    Ji Won Lee

    Full Text Available Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A subfamily, multi-drug resistance-associated protein 2 (MRP2 and breast cancer resistance protein (BCRP. A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3% patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing -1774 del and/or -24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79-28.67, P = 0.005. Creatinine elevation was observed in 9 patients (9.2%. Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7-43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34-150.35, P = 0.028. Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox.

  19. Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent

    Science.gov (United States)

    Lee, Ji Won; Kang, Hyoung Jin; Choi, Ji-Yeob; Kim, Nam Hee; Jang, Mi Kyung; Yeo, Chang-Woo; Lee, Sang Seop; Kim, Hyery; Park, June Dong; Park, Kyung Duk; Shin, Hee Young; Shin, Jae-Gook; Ahn, Hyo Seop

    2013-01-01

    Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing −1774 del and/or −24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79–28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7–43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34–150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox. PMID:23737969

  20. Synergistic Activities of an Efflux Pump Inhibitor and Iron Chelators against Pseudomonas aeruginosa Growth and Biofilm Formation

    DEFF Research Database (Denmark)

    Liu, Yang; Yang, Liang; Molin, Søren

    2010-01-01

    The efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PA beta N) was paired with iron chelators 2,2'-dipyridyl, acetohydroxamic acid, and EDTA to assess synergistic activities against Pseudomonas aeruginosa growth and biofilm formation. All of the tested iron chelators synergistically...... inhibited P. aeruginosa growth and biofilm formation with PA beta N. PA beta N-EDTA showed the most promising activity against P. aeruginosa growth and biofilm formation....

  1. Hydroxyiminodisuccinic acid (HIDS): A novel biodegradable chelating ligand for the increase of iron bioavailability and arsenic phytoextraction

    OpenAIRE

    Rahman, M. Azizur; Hasegawa, Hiroshi; Kadohashi, K.; Maki, Teruya; Ueda, Kazumasa

    2009-01-01

    The influence of biodegradable chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. Even though the growth solution contained sufficient Fe, the growth of rice seedlings gradually decreased up to 76% with the increase of pH of the solution from 7 to 11. Iron forms insoluble ferric hydroxide complexes at neutral or alkaline pH in oxic condition. Chelating ligands produce soluble 'Fe-ligand complex' which assist Fe uptake in pla...

  2. Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

    Science.gov (United States)

    Burke, Benjamin P.; Baghdadi, Neazar; Kownacka, Alicja E.; Nigam, Shubhanchi; Clemente, Gonçalo S.; Al-Yassiry, Mustafa M.; Domarkas, Juozas; Lorch, Mark; Pickles, Martin; Gibbs, Peter; Tripier, Raphaël; Cawthorne, Christopher; Archibald, Stephen J.

    2015-09-01

    The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging.The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no

  3. Assessment of antioxidative, chelating, and DNA-protective effects of selected essential oil components (eugenol, carvacrol, thymol, borneol, eucalyptol) of plants and intact Rosmarinus officinalis oil.

    Science.gov (United States)

    Horvathova, Eva; Navarova, Jana; Galova, Eliska; Sevcovicova, Andrea; Chodakova, Lenka; Snahnicanova, Zuzana; Melusova, Martina; Kozics, Katarina; Slamenova, Darina

    2014-07-16

    Selected components of plant essential oils and intact Rosmarinus officinalis oil (RO) were investigated for their antioxidant, iron-chelating, and DNA-protective effects. Antioxidant activities were assessed using four different techniques. DNA-protective effects on human hepatoma HepG2 cells and plasmid DNA were evaluated with the help of the comet assay and the DNA topology test, respectively. It was observed that whereas eugenol, carvacrol, and thymol showed high antioxidative effectiveness in all assays used, RO manifested only antiradical effect and borneol and eucalyptol did not express antioxidant activity at all. DNA-protective ability against hydrogen peroxide (H2O2)-induced DNA lesions was manifested by two antioxidants (carvacrol and thymol) and two compounds that do not show antioxidant effects (RO and borneol). Borneol was able to preserve not only DNA of HepG2 cells but also plasmid DNA against Fe(2+)-induced damage. This paper evaluates the results in the light of experiences of other scientists.

  4. Preparation and Bioavailability Analysis of Ferrous Bis Alanine Chelate as a New Micronutrient for Treatment of Iron Deficiency Anemia

    Science.gov (United States)

    Zargaran, Marzieh; Saadat, Ebrahim; Dinarvand, Rassoul; Sharifzadeh, Mohammad; Dorkoosh, Farid

    2016-01-01

    Purpose: One of the most nutritional disorders around the world is iron deficiency. A novel iron compound was synthesized by chelating ferrous ions with alanine for prevention and treatment of iron deficiency anemia. Methods: The newly synthesized compound was characterized both qualitatively and quantitatively by Fourier Transform Infrared (FT-IR) spectroscopy. The bioavailability of newly synthesized iron micronutrient was evaluated in four groups of Wistar rats. The group I was a negative control group and the other three groups received three different iron formulations. After 14 days, the blood samples were taken and analyzed accordingly. Results: Calculations showed that more than 91.8% of iron was incorporated in the chelate formulation. In vivo studies showed that serum iron, total iron binding capacity and hemoglobin concentrations were significantly increased in group IV, which received ferrous bis alanine chelate compared with the negative control group (p<0.05) and also group II, which received ferrous sulfate.7H2O (p<0.05). It indicates that the new formulation considerably improves the blood iron status compared with the conventional iron compounds. There were no significant differences (p<0.05) in the serum iron between group IV and group III, which received ferrous bis glycine. Conclusion: The results showed better bioavailability of ferrous bis alanine as a new micronutrient for treatment of iron deficiency anemia in comparison with ferrous sulfate. Ferrous bis alanine could be considered as a suitable supplement for prevention and treatment of iron deficiency anemia. PMID:27766225

  5. Degradation of toluene, ethylbenzene, and xylene using heat and chelated-ferrous iron activated persulfate oxidation

    Science.gov (United States)

    Mondal, P.; Sleep, B.

    2014-12-01

    Toluene, ethylbenze, and xylene (TEX) are common contaminants in the subsurface. Activated persulfate has shown promise for degrading a wide variety of organic compounds. However, studies of persulfate application for in situ degradation of TEX and effects on the subsequent bioremediation are limited. In this work, degradation studies of TEX in aqueous media and soil are being conducted using heat activated and chelated-ferrous iron activated persulfate oxidation in batch and flow-through column experiments. In the batch experiments, sodium persulfate is being used at different concentrations to provide an initial persulfate to TEX molar ratios between 10:1 and 100:1. Sodium persulfate solutions are being activated at 20, 37, 60, and 80 oC temperatures for the heat activated oxidation. For the chelated-ferrous iron activated oxidation, ferrous iron and citric acid, both are being used at concentration of 5 mM. In the experiments with soil slurry, a soil to water ratio of 1 to 5 is being used. Flow through water saturated column experiments are being conducted with glass columns (45 cm in length and 4 cm in diameter) uniformly packed with soils, and equilibrated with water containing TEX at the target concentrations. Both the heat activation and chelated-ferrous iron activation of persulfate are being employed in the column experiments. Future experiments are planned to determine the suitability of persulfate oxidation of TEX on the subsequent biodegradation using batch microcosms containing TEX degrading microbial cultures. In these experiments, the microbial biomass will be monitored using total phospholipids, and the microbial community will be determined using quantitative real-time polymerase chain reaction (qPCR) on the extracted DNA. This study is expected to provide suitable operating conditions for in situ chemical oxidation of TEX with activated persulfate followed by bioremediation.

  6. Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine.

    Science.gov (United States)

    Goswami, Dibakar; Vitorino, Hector A; Alta, Roxana Y P; Silvestre, Daniel M; Nomura, Cassiana S; Machini, M Teresa; Espósito, Breno P

    2015-10-01

    Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47-57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane.

  7. CARDIAC FUNCTION AND IRON CHELATION IN THALASSEMIA MAJOR AND INTERMEDIA: A REVIEW OF THE UNDERLYING PATHOPHYSIOLOGY AND APPROACH TO CHELATION MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Athanasios Aessopos

    2009-07-01

    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  8. Development and evaluation of the improved iron chelating agents EHPG, HBED and their dimethyl esters.

    Science.gov (United States)

    Hershko, C; Grady, R W; Link, G

    1984-01-01

    The phenolic EDTA analogues ethylenediamine-N,N'-bis-(2- hydroxyphenylglycine ) ( EHPG ), N,N'-bis(2-hydroxybenzyl)-ethylenediamine diacetic acid ( HBED ), and their respective dimethyl esters ( dimethylEHPG and dimethylHBED ) were studied in hypertransfused rats. Radioiron bound to these compounds was cleared mainly by the liver and excreted in the bile. After a single 40 mg i.m. injection, the percentage of radioiron removed from 59Fe-ferritin-labelled hepatocytes and excreted in the bile was 4% in untreated controls, 24% for desferral , 42% for dimethylEHPG , 58% for EHPG , 63% for HBED , and 80% for dimethylHBED . DimethylHBED combines oral effectiveness with superior chelating ability, selective hepatocellular action, and low apparent toxicity. It may represent a significant advance in the development of new iron chelating drugs.

  9. Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm.

    Science.gov (United States)

    Nazik, Hasan; Penner, John C; Ferreira, Jose A; Haagensen, Janus A J; Cohen, Kevin; Spormann, Alfred M; Martinez, Marife; Chen, Vicky; Hsu, Joe L; Clemons, Karl V; Stevens, David A

    2015-10-01

    Iron acquisition is crucial for the growth of Aspergillus fumigatus. A. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. In this study, we assessed the effects of Fe chelators on biofilm formation and development. Deferiprone (DFP), deferasirox (DFS), and deferoxamine (DFM) were tested for MIC against a reference isolate via a broth macrodilution method. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to DFP, DFM, DFP plus FeCl3, or FeCl3 alone. A preformed biofilm was exposed to DFP with or without FeCl3. The DFP and DFS MIC50 against planktonic A. fumigatus was 1,250 μM, and XTT gave the same result. DFM showed no planktonic inhibition at concentrations of ≤2,500 μM. By XTT testing, DFM concentrations of biofilms forming in A. fumigatus or preformed biofilms (P biofilm formation (P Biofilm formation with 625 μM DFP plus any concentration of FeCl3 was lower than that in the controls (P biofilms, DFP in the range of ≥625 to 1,250 μM was inhibitory compared to the controls (P biofilm formation (P biofilm increased with 2,500 μM FeCl3 only (P biofilms of A. fumigatus clinical isolates to DFP were noted. In conclusion, iron stimulates biofilm formation and preformed biofilms. Chelators can inhibit or enhance biofilms. Chelation may be a potential therapy for A. fumigatus, but we show here that chelators must be chosen carefully. Individual isolate susceptibility assessments may be needed.

  10. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Science.gov (United States)

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang

    2014-08-01

    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPOEPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate

  11. Modulatory effect of iron chelators on adenosine deaminase activity and gene expression in Trichomonas vaginalis.

    Science.gov (United States)

    Primon-Barros, Muriel; Rigo, Graziela Vargas; Frasson, Amanda Piccoli; Santos, Odelta dos; Smiderle, Lisiane; Almeida, Silvana; Macedo, Alexandre José; Tasca, Tiana

    2015-11-01

    Trichomonas vaginalis is a flagellate protozoan that parasitises the urogenital human tract and causes trichomoniasis. During the infection, the acquisition of nutrients, such as iron and purine and pyrimidine nucleosides, is essential for the survival of the parasite. The enzymes for purinergic signalling, including adenosine deaminase (ADA), which degrades adenosine to inosine, have been characterised in T. vaginalis. In the evaluation of the ADA profile in different T. vaginalis isolates treated with different iron sources or with limited iron availability, a decrease in activity and an increase in ADA gene expression after iron limitation by 2,2-bipyridyl and ferrozine chelators were observed. This supported the hypothesis that iron can modulate the activity of the enzymes involved in purinergic signalling. Under bovine serum limitation conditions, no significant differences were observed. The results obtained in this study allow for the assessment of important aspects of ADA and contribute to a better understanding of the purinergic system in T. vaginalis and the role of iron in establishing infection and parasite survival.

  12. Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation ▿ ††

    Science.gov (United States)

    Minear, Steven; O'Donnell, Allyson F.; Ballew, Anna; Giaever, Guri; Nislow, Corey; Stearns, Tim; Cyert, Martha S.

    2011-01-01

    Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G1 phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties. PMID:21908599

  13. Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

    Science.gov (United States)

    Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

    2009-01-01

    We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

  14. Wild Edible Fruit of Prunus nepalensis Ser. (Steud), a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

    Science.gov (United States)

    Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Das, Abhishek; Mandal, Nripendranath

    2015-01-01

    The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud), a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME) exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 30.92 ± 0.40 μg/ml). PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38). On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

  15. Chelating, antioxidant and hypoglycaemic potential of Muscari comosum (L.) Mill. bulb extracts.

    Science.gov (United States)

    Loizzo, Monica R; Tundis, Rosa; Menichini, Federica; Pugliese, Alessandro; Bonesi, Marco; Solimene, Umberto; Menichini, Francesco

    2010-12-01

    The metal chelating activity, antioxidant properties and the effect on carbohydrate-hydrolysing enzyme inhibition of Muscari comosum extracts have been investigated. M. comosum bulbs contain a total amount of the phenols with a value of 56.6 mg chlorogenic acid equivalent per gram of extract and a flavonoid content of 23.4 mg quercetin equivalent per gram of extract. In order to evaluate the non-polar constituents, n-hexane extract was obtained. Gas chromatography-mass spectrometry analysis revealed the presence of fatty acids and ethyl esters as major constituents, with different aldehydes and alkanes as minor components. Ethanolic extract had the highest ferric-reducing ability power (66.7 μM Fe(II)/g) and DPPH scavenging activity with a concentration giving 50% inhibition (IC₅₀) value of 40.9 μg/ml. Moreover, this extract exhibited a good hypoglycaemic activity with IC₅₀ values of 81.3 and 112.8 μg/ml for α-amylase and α-glucosidase, respectively. In conclusion, M. comosum bulbs show promising antioxidant and hypoglycaemic activity via the inhibition of carbohydrate digestive enzymes. These activities may be of interest from a functional point of view and for the revalorization of this ancient non-cultivated vegetable of Mediterranean traditional gastronomy.

  16. Regulation of copper and iron homeostasis by metal chelators: a possible chemotherapy for Alzheimer's disease.

    Science.gov (United States)

    Robert, Anne; Liu, Yan; Nguyen, Michel; Meunier, Bernard

    2015-05-19

    With the increase of life expectancy of humans in more than two-thirds of the countries in the World, aging diseases are becoming the frontline health problems. Alzheimer's disease (AD) is now one of the major challenges in drug discovery, since, with the exception of memantine in 2003, all clinical trials with drug candidates failed over the past decade. If we consider that the loss of neurons is due to a high level of oxidative stress produced by nonregulated redox active metal ions like copper linked to amyloids of different sizes, regulation of metal homeostasis is a key target. The difficulty for large copper-carrier proteins to directly extract copper ions from metalated amyloids might be considered as being at the origin of the rupture of the copper homeostasis regulation in AD brains. So, there is an urgent need for new specific metal chelators that should be able to regulate the homeostasis of metal ions, specially copper and iron, in AD brains. As a consequence of that concept, chelators promoting metal excretion from brain are not desired. One should favor ligands able to extract copper ions from sinks (amyloids being the major one) and to transfer these redox-active metal ions to copper-carrier proteins or copper-containing enzymes. Obviously, the affinity of these chelators for the metal ion should not be a sufficient criterion, but the metal specificity and the ability of the chelators to release the metal under specific biological conditions should be considered. Such an approach is still largely unexplored. The requirements for the chelators are very high (ability to cross the brain-blood barrier, lack of toxicity, etc.), few chemical series were proposed, and, among them, biochemical or biological data are scarce. As a matter of fact, the bioinorganic pharmacology of AD represents less than 1% of all articles dedicated to AD drug research. The major part of these articles deals with an old and rather toxic drug, clioquinol and related analogs, that

  17. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

    Science.gov (United States)

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-05-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

  18. New hydroxypyridinone iron-chelators as potential anti-neurodegenerative drugs.

    Science.gov (United States)

    Arduino, Daniela; Silva, Daniel; Cardoso, Sandra M; Chaves, Silvia; Oliveira, Catarina R; Santos, M Amelia

    2008-05-01

    The neuroprotective action of a set of new hydroxypyridinone-based (3,4-HP) compounds (A, B and C), which are iron chelators extra-functionalized with a propargylamino group for potential MAO-B inhibition, was evaluated after cell treatment with MPP+ (an in vivo inducer of parkinsonism) and Abeta(1-40) and/or Abeta(1-42) peptides. Our results show that all these compounds improved cell viability in cells treated with MPP+ and Abeta(1-40) peptide or Abeta(1-42) peptide. In order to evaluate the cellular mechanisms underlying the activity of these compounds, we studied their protective role in caspase activation. All compounds tested were able to prevent MPP+ and Brefeldin A induced caspase-2 activation. They also showed quite effective in the inhibition of caspase-4 and caspase-3 activity, an effector caspase in the apoptotic process. Finally, detection of apoptotic-like cell death after cell exposure to MPP+ was also performed by TUNEL assay. Our results demonstrated that all tested compounds prevented DNA fragmentation by decreasing TUNEL positive cells. A, B and C were more effective than DFP (a 3,4-HP iron-chelating agent in clinical use) in MPP+ induced cell death. Therefore, these results evidenced a neuroprotective and antiapoptotic role for the compounds studied.

  19. Mechanism of the antitumoral activity of deferasirox, an iron chelation agent, on mantle cell lymphoma.

    Science.gov (United States)

    Vazana-Barad, Liat; Granot, Galit; Mor-Tzuntz, Rahav; Levi, Itai; Dreyling, Martin; Nathan, Ilana; Shpilberg, Ofer

    2013-04-01

    Mantle cell lymphoma (MCL) characterized by the t(11;14)(q13;q32) translocation, resulting in cyclin D1 overexpression, is one of the most challenging lymphomas to treat. Iron chelators, such as deferasirox, have previously been shown to exhibit anti-proliferative properties; however, their effect on MCL cells has never been investigated. We showed that deferasirox exhibited antitumoral activity against the MCL cell lines HBL-2, Granta-519 and Jeko-1, with 50% inhibitory concentration (IC(50)) values of 7.99 ± 2.46 μM, 8.93 ± 2.25 μM and 31.86 ± 7.26 μM, respectively. Deferasirox induced apoptosis mediated through caspase-3 activation and decreased cyclin D1 protein levels resulting from increased proteasomal degradation. We also demonstrated down-regulation of phosphor-RB (Ser780) expression, which resulted in increasing levels of the E2F/RB complex and G(1)/S arrest. Finally, we showed that deferasirox activity was dependent on its iron chelating ability. The present data indicate that deferasirox, by down-regulating cyclin D1 and inhibiting its related signals, may constitute a promising adjuvant therapeutic molecule in the strategy for MCL treatment.

  20. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

    Science.gov (United States)

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-01-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

  1. Iron-chelating agent, deferasirox, inhibits neutrophil activation and extracellular trap formation.

    Science.gov (United States)

    Kono, Mari; Saigo, Katsuyasu; Yamamoto, Shiori; Shirai, Kohei; Iwamoto, Shuta; Uematsu, Tomoko; Takahashi, Takayuki; Imoto, Shion; Hashimoto, Makoto; Minami, Yosuke; Wada, Atsushi; Takenokuchi, Mariko; Kawano, Seiji

    2016-10-01

    Iron-chelating agents, which are frequently prescribed to transfusion-dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron-chelating agent, inhibits phorbol myristate acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP)-induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double-stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5-100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose-independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET-related adverse effects, including ALI and thrombosis.

  2. The proceedings of the 17th International Conference on Chelation: application of effective chelation therapies in iron loading and non iron loading conditions, and the gap in the prevention and treatment policies on thalassemia between developed and developing countries.

    Science.gov (United States)

    Kontoghiorghes, George J

    2009-01-01

    Substantial progress in the use of chelating drugs for the treatment of iron overload and of non iron loading conditions has been presented during the 17th International Conference on Chelation (ICOC) held in November 2007 at Shenzhen, China. Major challenges lie ahead for the prevention and treatment of thalassemia in China, India, Thailand, Indonesia and many other developing countries where millions of heterozygote thalassemia carriers live and thousands of homozygote thalassemia patients are born annually. The progressive improvement of the economic climate in developing countries will increase the demand and resources for more prenatal and antenatal diagnoses, transfusions and chelation therapy in forthcoming years. Despite the major advances in diagnosis and treatment in developed countries, the vast majority of thalassemia patients in developing countries die untreated because they cannot afford the cost of transfusions and chelation therapy. New approaches and infrastructures and more efforts are needed to overcome the difficulties of supplying new techniques and treatments to patients in developing countries. International and local organizations need to be persuaded to act collectively and effectively to improve chelation and related treatments for thalassemia and other conditions, especially at this time that universally effective and inexpensive chelation therapies can be applied.

  3. Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: the safety profile of deferasirox

    Science.gov (United States)

    Taher, Ali T; Porter, John B; Viprakasit, Vip; Kattamis, Antonis; Chuncharunee, Suporn; Sutcharitchan, Pranee; Siritanaratkul, Noppadol; Origa, Raffaella; Karakas, Zeynep; Habr, Dany; Zhu, Zewen; Cappellini, M Domenica

    2014-01-01

    Objective Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3. Methods THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2). Results Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment. Conclusions The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation. PMID:24460655

  4. Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation.

    Science.gov (United States)

    Meo, Anna; Ruggeri, Annalisa; La Rosa, Maria A; Zanghì, Laura; Morabito, Nancy; Duca, Lorena

    2006-01-01

    In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.

  5. Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

    Science.gov (United States)

    Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru

    2010-01-01

    Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762

  6. Iron Chelation Therapy with Deferasirox Results in Improvement of Liver Enzyme Level in Patients with Iron Overload-Associated Liver Dysfunction

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    Yasuo Miura

    2010-01-01

    Full Text Available Iron chelation therapy (ICT has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX, a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT. All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level.

  7. Selection of Chelated Fe (III)/Fe (II) Catalytic Oxidation Agents for Desulfurization Based on Iron Complexation Method

    Institute of Scientific and Technical Information of China (English)

    Luo Ying; Liu Youzhi; Qi Guisheng; Guo Huidong; Zhu Zhengfeng

    2014-01-01

    Optimization of factors inlfuencing the experiments on reactions involving 8 different chelating agents and sol-uble Fe (III)/Fe (II) salts was carried out to yield chelated iron complexes. A combination of optimized inlfuencing factors has resulted in a Fe chelating capacity of the iron-based desulfurization solution to be equal to 6.83—13.56 g/L at a redox potential of 0.185—0.3. The desulfurization performance of Fe (III)/Fe (II) chelating agents was investigated on a simulated sulfur-containing industrial gas composed of H2S and N2 in a cross-lfow rotating packed bed. Test results have revealed that the proposed iron-based desulfurization solution showed a sulfur removal efifciency of over 99%along with a Fe chelating capacity exceeding 1.35 g/L. This desulfurization technology which has practical application prospect is currently in the phase of commercial scale-up study.

  8. Iron Hydride Detection and Intramolecular Hydride Transfer in a Synthetic Model of Mono-Iron Hydrogenase with a CNS Chelate.

    Science.gov (United States)

    Durgaprasad, Gummadi; Xie, Zhu-Lin; Rose, Michael J

    2016-01-19

    We report the identification and reactivity of an iron hydride species in a synthetic model complex of monoiron hydrogenase. The hydride complex is derived from a phosphine-free CNS chelate that includes a Fe-C(NH)(═O) bond (carbamoyl) as a mimic of the active site iron acyl. The reaction of [((O═)C(HN)N(py)S(Me))Fe(CO)2(Br)] (1) with NaHBEt3 generates the iron hydride intermediate [((O═)C(HN)N(py)S(Me))Fe(H)(CO)2] (2; δFe-H = -5.08 ppm). Above -40 °C, the hydride species extrudes CH3S(-) via intramolecular hydride transfer, which is stoichiometrically trapped in the structurally characterized dimer μ2-(CH3S)2-[((O═)C(HN)N(Ph))Fe(CO)2]2 (3). Alternately, when activated by base ((t)BuOK), 1 undergoes desulfurization to form a cyclometalated species, [((O═)C(NH)NC(Ph))Fe(CO)2] (5); derivatization of 5 with PPh3 affords the structurally characterized species [((O═)C(NH)NC)Fe(CO)(PPh3)2] (6), indicating complex 6 as the common intermediate along each pathway of desulfurization.

  9. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

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    Kontoghiorghe CN

    2016-01-01

    Full Text Available Christina N Kontoghiorghe, George J Kontoghiorghes Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, Cyprus Abstract: The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM. Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO, oral deferiprone (L1, and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve

  10. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease.

    Science.gov (United States)

    Brazier, Marcus W; Wedd, Anthony G; Collins, Steven J

    2014-04-21

    Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.

  11. Antioxidant and Metal Chelation-Based Therapies in the Treatment of Prion Disease

    Directory of Open Access Journals (Sweden)

    Marcus W. Brazier

    2014-04-01

    Full Text Available Many neurodegenerative disorders involve the accumulation of multimeric assemblies and amyloid derived from misfolded conformers of constitutively expressed proteins. In addition, the brains of patients and experimental animals afflicted with prion disease display evidence of heightened oxidative stress and damage, as well as disturbances to transition metal homeostasis. Utilising a variety of disease model paradigms, many laboratories have demonstrated that copper can act as a cofactor in the antioxidant activity displayed by the prion protein while manganese has been implicated in the generation and stabilisation of disease-associated conformers. This and other evidence has led several groups to test dietary and chelation therapy-based regimens to manipulate brain metal concentrations in attempts to influence the progression of prion disease in experimental mice. Results have been inconsistent. This review examines published data on transition metal dyshomeostasis, free radical generation and subsequent oxidative damage in the pathogenesis of prion disease. It also comments on the efficacy of trialed therapeutics chosen to combat such deleterious changes.

  12. Effect of Systemic Iron Overload and a Chelation Therapy in a Mouse Model of the Neurodegenerative Disease Hereditary Ferritinopathy

    Science.gov (United States)

    Li, Wei; Goodwin, Charles B.; Richine, Briana; Acton, Anthony; Chan, Rebecca J.; Peacock, Munro; Muhoberac, Barry B.; Ghetti, Bernardino; Vidal, Ruben

    2016-01-01

    Mutations in the ferritin light chain (FTL) gene cause the neurodegenerative disease neuroferritinopathy or hereditary ferritinopathy (HF). HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic iron-containing ferritin inclusion bodies (IBs) in glia and neurons throughout the central nervous system (CNS) and in tissues of multiple organ systems. Herein, using primary mouse embryonic fibroblasts from a mouse model of HF, we show significant intracellular accumulation of ferritin and an increase in susceptibility to oxidative damage when cells are exposed to iron. Treatment of the cells with the iron chelator deferiprone (DFP) led to a significant improvement in cell viability and a decrease in iron content. In vivo, iron overload and DFP treatment of the mouse model had remarkable effects on systemic iron homeostasis and ferritin deposition, without significantly affecting CNS pathology. Our study highlights the role of iron in modulating ferritin aggregation in vivo in the disease HF. It also puts emphasis on the potential usefulness of a therapy based on chelators that can target the CNS to remove and redistribute iron and to resolubilize or prevent ferritin aggregation while maintaining normal systemic iron stores. PMID:27574973

  13. Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

    Science.gov (United States)

    Sofic, E; Salkovic-Petrisic, M; Tahirovic, I; Sapcanin, A; Mandel, S; Youdim, M; Riederer, P

    2015-04-01

    Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.

  14. Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet.

    Science.gov (United States)

    El, Sedef Nehir; Karakaya, Sibel

    2004-02-01

    This study aimed at evaluating the antioxidative activity of nine different families of greens. Raphanus raphanistrum (wild radish), Anchusa azurea (bugloss), Daucus carota (wild carrot), Sonchus oleraceus (sowthistle), Papaver rhoeas (corn poppy), Malva sylvestris (blue mallow), Foeniculum vulgare (fennel), Cichorium intybus (chicory) and Salicornia europaea (jointed glasswort) are native to the Mediterranean and are commonly consumed as a salad or an ingredient in some recipes. The antioxidative activities, including the radical scavenging effects, inhibition of hydrogen peroxide (H(2)O(2)), and Fe(2+)-chelating activity, were studied. All samples showed antioxidant activity as a radical scavenger in the experiment using the DPPH* radical. The ratio between the slopes of the kinetic model was used to compare antioxidant efficiency of different greens. Greens also possessed antioxidative activity toward H(2)O(2). Especially, greens exhibited a marked scavenging effect on H(2)O(2) at 0.2 g/ml concentration. The Fe(2+) ion-chelating activities of the samples except jointed glasswort were greater than 70%. The antioxidant activity of samples with different methods based on the inhibition of different reactions could not be compared. The current dietary guidelines include recommendations for an increase in the consumption of plant foods. Greens should provide an optimal supply of antioxidant substances in the diet.

  15. The hexadentate hydroxypyridinonate TREN-(Me-3,2-HOPO) is a more orally active iron chelator than its bidentate analogue.

    Science.gov (United States)

    Yokel, R A; Fredenburg, A M; Durbin, P W; Xu, J; Rayens, M K; Raymond, K N

    2000-04-01

    Bidentate hydroxypyridinone chelators effectively complex and facilitate excretion of trivalent iron. To test the hypothesis that hexadentate chelators are more effective than bidentate chelators at low concentrations, urinary and biliary Fe excretions were determined in Fe-loaded rats before and after administration of a bidentate chelator, Pr-(Me-3,2-HOPO), or its hexadentate analogue, TREN-(Me-3,2-HOPO). The bidentate chelator slightly increased biliary Fe excretion in Fe-loaded rats after IV (90 micromol/kg) and PO (90 or 270 micromol/kg) administration, but chelation efficiency did not exceed 1%. The hexadentate chelator markedly increased biliary Fe excretion, achieving overall chelation efficiencies of 14% after IV administration of 30 micromol/kg and 8 or 3% after PO (30 or 90 micromol/kg) administration. The hexadentate chelator was significantly more effective than the bidentate chelator after IV injection and oral dosing. In chelator-treated Fe-loaded or saline-injected rats, >90% of the excreted Fe was in the bile. Oral TREN-(Me-3,2-HOPO), given to non-Fe-loaded rats, did not appreciably change Fe output, indicating that there was little Fe depletion in the absence of Fe overload. These results support the hypothesis that greater Fe chelation efficiency can be achieved with hexadentate than with bidentate chelators at lower, and presumably safer, concentrations. The results also demonstrate that TREN-(Me-3, 2-HOPO) is a promising, orally effective, Fe chelator.

  16. An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice.

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    Nikhil Baban Ghate

    Full Text Available Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls' staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38 cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a

  17. An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice.

    Science.gov (United States)

    Ghate, Nikhil Baban; Chaudhuri, Dipankar; Das, Abhishek; Panja, Sourav; Mandal, Nripendranath

    2015-01-01

    Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls' staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for

  18. Iron-[S,S']-EDDS (FeEDDS) Chelate as an Iron Source for Horticultural Crop Production: Marigold Growth and Nutrition, Spectral Properties, and Photodegradation

    Science.gov (United States)

    Aminopolycarboxylic acid (APCA) complexones, commonly referred to as ligands or chelating agents, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to p...

  19. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

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    Alexandros Makis

    2013-01-01

    Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

  20. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

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    Murtadha Al-Khabori

    2013-03-01

    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  1. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Science.gov (United States)

    Al-Khabori, Murtadha; Bhandari, Sunil; Al-Huneini, Mohammed; Al-Farsi, Khalil; Panjwani, Vinodh; Daar, Shahina

    2013-01-01

    Objectives Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. Methods A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Results Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). Conclusion Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings. PMID:23599881

  2. Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate.

    Science.gov (United States)

    Dairam, Amichand; Fogel, Ronen; Daya, Santy; Limson, Janice L

    2008-05-14

    Research demonstrates that antioxidants and metal chelators may be of beneficial use in the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). This study investigated the antioxidant and metal-binding properties of curcumin, capsaicin, and S-allylcysteine, which are major components found in commonly used dietary spice ingredients turmeric, chilli, and garlic, respectively. The DPPH assay demonstrates that these compounds readily scavenge free radicals. These compounds significantly curtail iron- (Fe2+) and quinolinic acid (QA)-induced lipid peroxidation and potently scavenge the superoxide anion generated by 1 mM cyanide in rat brain homogenate. The ferrozine assay was used to measure the extent of Fe2+ chelation, and electrochemistry was employed to measure the Fe3+ binding activity of curcumin, capsaicin, and S-allylcysteine. Both assays demonstrate that these compounds bind Fe2+ and Fe3+ and prevent the redox cycling of iron, suggesting that this may be an additional method through which these agents reduce Fe2+-induced lipid peroxidation. This study demonstrates the antioxidant and metal-binding properties of these spice ingredients, and it is hereby postulate that these compounds have important implications in the prevention or treatment of neurodegenerative diseases such as AD.

  3. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

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    Carpenter JP

    2011-09-01

    Full Text Available Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM patients. Treatment effects with improved left ventricular (LV ejection fraction (EF have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR to the relative risk (RR of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM and 63-70% (lower half of the normal range for TM. Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

  4. The Oral Iron Chelator, Deferasirox, Reverses the Age-Dependent Alterations in Iron and Amyloid-β Homeostasis in Rat Brain: Implications in the Therapy of Alzheimer's Disease.

    Science.gov (United States)

    Banerjee, Priyanjalee; Sahoo, Arghyadip; Anand, Shruti; Bir, Aritri; Chakrabarti, Sasanka

    2016-01-01

    The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimer's disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-β (Aβ) peptide homeostasis in the aging brain, such as an increased production of the amyloid-β protein precursor, a decreased level of neprilysin, and increased accumulation of Aβ42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered Aβ peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NF-κB in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in Aβ peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and Aβ peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimer's disease.

  5. Terapia quelante oral com deferiprona em pacientes com sobrecarga de ferro Oral iron chelator therapy with deferiprone in patients with overloaded iron

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    Antonio Fabron Jr

    2003-01-01

    Full Text Available Apesar da introdução da quelação parenteral de ferro com desferoxamina há mais de trinta anos, 50% dos pacientes com talassemia major morrem antes dos 35 anos de idade, predominantemente por insuficiência cardíaca secundária a sobrecarga de ferro. Embora a desferrioxamina, possa reduzir ou estabilizar o acúmulo de ferro no corpo, um grande número de pacientes não recebe terapia adequada com este quelante devido principalmente à intolerância a um regime que requer administração parenteral prolongada, cinco a sete dias por semana. Para esses pacientes, a deferiprona, um quelante oralmente ativo, surge com uma alternativa de tratamento para o controle da sobrecarga de ferro. Um grande número de estudos clínicos demonstraram a segurança e eficácia da deferiprona. Estima-se que mais de 6 mil pacientes com sobrecarga de ferro já tenham sido tratados com este quelante, com alguns pacientes tomando a droga por mais de dez anos. A quantidade de ferro excretada induzida pela deferiprona é diretamente influenciada pela dose da droga e pelo grau de sobrecarga de ferro do paciente. Recentemente, demonstrou-se que desferrioxamina e deferiprona exibem capacidades quelantes diversas e que, usados simultaneamente ou numa terapia sequencial, promovem uma excreção de ferro adicional ou sinérgica com rápida redução na carga de ferro do corpo. Pela primeira vez é possível considerar esquemas de quelação individualizados baseados nas necessidades individuais de cada paciente.Despite the introduction of the parenteral iron chelator desferrioxamine more than 30 years ago, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. Although desferrioxamine can reduce or stabilize the iron load, many patients still do not receive adequate chelation mainly due to its cumbersome mode of administration which impairs the compliance with the regime of repeatedly subcutaneous infusions

  6. Flotation of a new chelate collector on fine refractory iron ore-containing carbonate

    Institute of Scientific and Technical Information of China (English)

    王婷霞; 朱一民; 桂夏辉

    2016-01-01

    A suitable and efficient flotation collector at normal atmospheric temperature for Donganshan iron ore was developed. A new chelate collector W-2 was synthesized. At 30 °C, condition flotation tests on mixed magnetic concentrate of Donganshan sintering plant established the best reagent system. With the optimum reagent system, one direct flotation and one reverse flotation including one roughing, one cleaning and two scavenging stages have been conducted. After closed-circuit flotation, excellent indices were obtained with grade of siderite concentrate of 36.49%, recovery rate of 10.65%, and loss on ignition of 11.17%, and the grade of hematite concentrate reached 66.27%, with recovery rate of 78.25%, tailing grade of 16.22%, and recovery rate of 11.10%. To analyze the mechanism of action from W-2 to quartz and siderite, zeta potential and FTIR spectra were detected. Results showed that after reaction with W-2, the zeta potential of quartz and siderite evidently changed, which resulted from hydrogen bond between quartz and W-2, and a certain chemical action between siderite and W-2. In addition, the electronegativity equalization principle was used to calculate electronegativity of active adsorption sites and analysis on reagent molecular structure showed that W-2 molecule had five active adsorption sites. Results showed that the electronegativity of atoms N and O in W-2 presented a substantial increase, and the synergy of atomic sites allowed considerable enhancement of collecting ability.

  7. Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis

    Science.gov (United States)

    Chen, Wen-Jen; Kuo, Tzu-Yen; Hsieh, Feng-Chia; Chen, Pi-Yu; Wang, Chang-Sheng; Shih, Yu-Ling; Lai, Ying-Mi; Liu, Je-Ruei; Yang, Yu-Liang; Shih, Ming-Che

    2016-01-01

    Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive rice diseases worldwide. Therefore, in addition to breeding disease-resistant rice cultivars, it is desirable to develop effective biocontrol agents against Xoo. Here, we report that a soil bacterium Pseudomonas taiwanensis displayed strong antagonistic activity against Xoo. Using matrix-assisted laser desorption/ionization imaging mass spectrometry, we identified an iron chelator, pyoverdine, secreted by P. taiwanensis that could inhibit the growth of Xoo. Through Tn5 mutagenesis of P. taiwanensis, we showed that mutations in genes that encode components of the type VI secretion system (T6SS) as well as biosynthesis and maturation of pyoverdine resulted in reduced toxicity against Xoo. Our results indicated that T6SS is involved in the secretion of endogenous pyoverdine. Mutations in T6SS component genes affected the secretion of mature pyoverdine from the periplasmic space into the extracellular medium after pyoverdine precursor is transferred to the periplasm by the inner membrane transporter PvdE. In addition, we also showed that other export systems, i.e., the PvdRT-OpmQ and MexAB-OprM efflux systems (for which there have been previous suggestions of involvement) and the type II secretion system (T2SS), are not involved in pyoverdine secretion. PMID:27605490

  8. Wild Edible Fruit of Prunus nepalensis Ser. (Steud, a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

    Directory of Open Access Journals (Sweden)

    Dipankar Chaudhuri

    Full Text Available The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud, a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical (IC50 = 30.92 ± 0.40 μg/ml. PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 μg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38. On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

  9. Sobrecarga e quelação de ferro na anemia falciforme Iron overload and iron chelation in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Rodolfo D. Cançado

    2007-09-01

    Full Text Available Pacientes cronicamente transfundidos desenvolvem sobrecarga de ferro que ocasiona lesão orgânica e morte. Nos últimos trinta anos, pacientes com sobrecarga de ferro transfusional dependem de infusões noturnas de desferroxamina para quelação de ferro. Apesar da dramática melhora da expectativa de vida na era da desferroxamina para pacientes com anemias dependentes de transfusão, 50% dos pacientes com talassemia maior morrem antes dos 30 anos de idade, predominantemente devido à insuficiência cardíaca induzida pelo ferro. A difícil natureza desse tratamento com infusão subcutânea prolongada por meio de aparelho infusor portátil motivou o desenvolvimento de formas alternativas de tratamento que facilitasse a aderência do paciente. Estratégias para reduzir a sobrecarga de ferro e suas conseqüências, através da melhora dos regimes de quelação, foram as prioridades mais importantes nos últimos anos. Nesta revisão, descrevemos os avanços mais importantes da terapia quelante de ferro. Em particular, analisamos os dois quelantes de ferro ativos por via oral: deferiprona e o novo quelante de ferro oral deferasirox.Patients who are chronically dependent on transfusions will develop iron overload that leads to organ damage and eventually to death. For nearly 30 years, patients with transfusional iron overload have been subject to overnight deferoxamine infusions for iron chelation. Despite dramatic gains in terms of life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, 50% of patients with thalassemia major die before the age of 35 years, predominantly due to iron-induced heart failure. The very demanding nature of this treatment with prolonged subcutaneous infusion via portable pump infusions has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients' compliance. Strategies to reduce iron overload and its consequences by improving chelation

  10. Hydroxyiminodisuccinic acid (HIDS): A novel biodegradable chelating ligand for the increase of iron bioavailability and arsenic phytoextraction.

    Science.gov (United States)

    Rahman, M Azizur; Hasegawa, H; Kadohashi, K; Maki, T; Ueda, K

    2009-09-01

    The influence of biodegradable chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. Even though the growth solution contained sufficient Fe, the growth of rice seedlings gradually decreased up to 76% with the increase of pH of the solution from 7 to 11. Iron forms insoluble ferric hydroxide complexes at neutral or alkaline pH in oxic condition. Chelating ligands produce soluble 'Fe-ligand complex' which assist Fe uptake in plants. The biodegradable chelating ligand hydroxyiminodisuccinic acid (HIDS) was more efficient then those of ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS), and iminodisuccinic acid (IDS) in the increase of Fe uptake and growth of rice seedling. A total of 79+/-20, 87+/-6, 116+/-15, and 63+/-18mg dry biomass of rice seedlings were produced with the addition of 0.5mM of EDDS, EDTA, HIDS, and IDS in the nutrient solution, respectively. The Fe concentrations in rice tissues were 117+/-15, 82+/-8, 167+/-25, and 118+/-22micromolg(-1) dry weights when 0.25mM of EDDS, EDTA, HIDS, and IDS were added to the nutrient solution, respectively. Most of the Fe accumulated in rice tissues was stored in roots after the addition of chelating ligands in the solution. The results indicate that the HIDS would be a potential alternative to environmentally persistent EDTA for the increase of Fe uptake and plant growth. The HIDS also increased As uptake in rice root though its translocation from root to shoot was not augmented. This study reports HIDS for the first time as a promising chelating ligand for the enhancement of Fe bioavailability and As phytoextraction.

  11. Role of iron in inducing oxidative stress in thalassemia: Can it be prevented by inhibition of absorption and by antioxidants?

    Science.gov (United States)

    Rachmilewitz, Eliezer A; Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rechavi, Gideon; Breda, Laura; Rivella, Stefano; Cabantchik, Z Ioav

    2005-01-01

    The pathophysiology of thalassemia is, to a certain extent, associated with the generation of labile iron in the pathological red blood cell (RBC). The appearance of such forms of iron at the inner and outer cell surfaces exposes the cell to conditions whereby the labile metal promotes the formation of reactive oxygen species (ROS) leading to cumulative cell damage. Another source of iron accumulation results from increased absorption due to decreased expression of hepcidin. The presence of labile plasma iron (LPI) was carried out using fluorescent probes in the FACS. RNA expression of hepcidin was measured in two models of thalassemic mice. Hepcidin expression was also measured in human hepatoma HepG2 cells following incubation with thalassemic sera. LPI was identified and could be quantitatively measured and correlated with other parameters of iron overload. Hepcidin expression was downregulated in the livers of thalassemic mice, in major more than in intermedia. Thalassemic sera down regulated hepcidin expression in HepG2 liver cells. A possible way to decrease iron absorption could be by modulating hepcidin expression pharmacologically, by gene therapy or by its administration. Treatment with combination of antioxidants such as N-acetylcysteine for proteins and vitamin E for lipids in addition to iron chelators could neutralize the deleterious effects of ROS and monitored by quantitation of LPI.

  12. The novel multi-target iron chelator, M30 modulates HIF-1α-related glycolytic genes and insulin signaling pathway in the frontal cortex of APP/PS1 Alzheimer's disease mice.

    Science.gov (United States)

    Mechlovich, Danit; Amit, Tamar; Bar-Am, Orit; Mandel, Silvia; Youdim, Moussa B H; Weinreb, Orly

    2014-02-01

    Increasing evidence suggests that dysregulation of brain insulin/insulin receptor (InsR) and insulin signaling cascade are associated with the pathogenesis of Alzheimer's disease (AD). Our group has designed and synthesized a series of multi-target iron chelating, brain permeable compounds for AD. One leading multi-target compound, M30 possesses the neuroprotective N-propargyl moiety of the anti-Parkinsonian, monoamine oxidase (MAO)-B inhibitor, rasagiline (Azilect®) and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Positive outcomes for the behavioral/cognitive and neuroprotective effects of M30 were recently obtained in preclinical experimental studies, regarding pathological aspects relevant to ageing and AD. We report that chronic treatment with M30 (1 and 5 mg/kg p.o; three times a week for 9 months) significantly elevated cortical insulin and InsR transcript and protein expression, respectively and increased the phosphorylated form of glycogen synthase kinase-3β in the frontal cortex of amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice. In addition, M30 treatment upregulated the levels of hypoxia-inducible factor (HIF)-1α and expression of its target genes involved in glycolysis including, aldolase A, enolase-1 and glucose transporter-1 (Glut-1), in the frontal cortex of APP/PS1 mice. Treatment with M30 also lead to an increase in the hepatic protein expression levels of InsR and Glut-1 and lowered the increase in blood glucose levels following glucose tolerance test. The present findings indicate that the multifunctional iron chelating drug, M30 regulates major brain glucose metabolism parameters and thus, might be beneficial for AD, in which impaired neuronal insulin signaling and Glut expression have been implicated.

  13. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test

    Directory of Open Access Journals (Sweden)

    Barros Marcelo P

    2012-06-01

    Full Text Available Abstract Background Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old immediately before and 5 and 60 min after the exhaustive Wingate test. Results Maximum anaerobic power was improved by acute creatine supplementation (10.5 %, but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP, leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects. Conclusions Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent and inherent antioxidant activity of creatine.

  14. Affinity purification of copper chelating peptides from chickpea protein hydrolysates.

    Science.gov (United States)

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-05-16

    Chickpea protein hydrolysates obtained with alcalase and flavourzyme were used for purification of copper chelating peptides by affinity chromatography using copper immobilized on solid supports. The chelating activity of purified peptides was indirectly measured by the inhibition of beta-carotene oxidation in the presence of copper. Two protein hydrolysates, obtained after 10 and 100 min of hydrolysis, were the most inhibitory of beta-carotene oxidation. Purified copper chelating peptides from these protein hydrolysates contained 19.7 and 35.1% histidine, respectively, in comparison to 2.7 and 2.6% in the protein hydrolysates. Chelating peptides from hydrolysate obtained after 10 min of hydrolysis were the most antioxidative being 8.3 times more antioxidative than the hydrolysate, while chelating peptides purified from protein hydrolysate obtained after 100 min were 3.1 times more antioxidative than its hydrolysate. However, the histidine content was higher in peptides derived from the 100 min hydrolysate (19.7 against 35.1% in 10 min hydrolysate), indicating that this amino acid is not the only factor involved in the antioxidative activity, and other factors such as peptide size or amino acid sequence are also determinant. This manuscript shows that affinity chromatography is a useful procedure for purification of copper chelating peptides. This method can be extended to other metals of interest in nutrition, such as calcium, iron, or zinc. Purified chelating peptides, in addition to their antioxidative properties, may also be useful in food mineral fortification for increasing the bioavailability of these metals.

  15. Factors influencing the DNA nuclease activity of iron, cobalt, nickel, and copper chelates.

    Science.gov (United States)

    Joyner, Jeff C; Reichfield, Jared; Cowan, J A

    2011-10-05

    A library of complexes that included iron, cobalt, nickel, and copper chelates of cyclam, cyclen, DOTA, DTPA, EDTA, tripeptide GGH, tetrapeptide KGHK, NTA, and TACN was evaluated for DNA nuclease activity, ascorbate consumption, superoxide and hydroxyl radical generation, and reduction potential under physiologically relevant conditions. Plasmid DNA cleavage rates demonstrated by combinations of each complex and biological co-reactants were quantified by gel electrophoresis, yielding second-order rate constants for DNA(supercoiled) to DNA(nicked) conversion up to 2.5 × 10(6) M(-1) min(-1), and for DNA(nicked) to DNA(linear) up to 7 × 10(5) M(-1) min(-1). Relative rates of radical generation and characterization of radical species were determined by reaction with the fluorescent radical probes TEMPO-9-AC and rhodamine B. Ascorbate turnover rate constants ranging from 3 × 10(-4) to 0.13 min(-1) were determined, although many complexes demonstrated no measurable activity. Inhibition and Freifelder-Trumbo analysis of DNA cleavage supported concerted cleavage of dsDNA by a metal-associated reactive oxygen species (ROS) in the case of Cu(2+)(aq), Cu-KGHK, Co-KGHK, and Cu-NTA and stepwise cleavage for Fe(2+)(aq), Cu-cyclam, Cu-cyclen, Co-cyclen, Cu-EDTA, Ni-EDTA, Co-EDTA, Cu-GGH, and Co-NTA. Reduction potentials varied over the range from -362 to +1111 mV versus NHE, and complexes demonstrated optimal catalytic activity in the range of the physiological redox co-reactants ascorbate and peroxide (-66 to +380 mV).

  16. Removal of Fe3+ and Zn2+ from plasma metalloproteins by iron chelating therapeutics depicted with SEC-ICP-AES.

    Science.gov (United States)

    Sooriyaarachchi, Melani; Gailer, Jürgen

    2010-08-28

    The iron chelation therapy drugs desferrioxamine B (DFO) and deferiprone (DFP) are used to treat iron overload patients, but not much is known about their adverse effects on other essential metals in vivo. After the addition of a clinically relevant dose of DFP or an equimolar dose of DFO to human plasma in vitro, the mixtures were analyzed by size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES). Simultaneous detection of the emission lines of copper, iron and zinc allowed the visualization of changes that these drugs exerted at the metalloprotein level. After the addition of DFP, a metalloprotein level. Thus, SEC-ICP-AES emerges as a useful analytical tool to visualize health-relevant bioinorganic chemistry-related reactions of medicinal drugs in blood plasma in vitro.

  17. Effective sulfur and energy recovery from hydrogen sulfide through incorporating an air-cathode fuel cell into chelated-iron process.

    Science.gov (United States)

    Sun, Min; Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi

    2013-12-15

    The chelated-iron process is among the most promising techniques for the hydrogen sulfide (H2S) removal due to its double advantage of waste minimization and resource recovery. However, this technology has encountered the problem of chelate degradation which made it difficult to ensure reliable and economical operation. This work aims to develop a novel fuel-cell-assisted chelated-iron process which employs an air-cathode fuel cell for the catalyst regeneration. By using such a process, sulfur and electricity were effectively recovered from H2S and the problem of chelate degradation was well controlled. Experiment on a synthetic sulfide solution showed the fuel-cell-assisted chelated-iron process could maintain high sulfur recovery efficiencies generally above 90.0%. The EDTA was preferable to NTA as the chelating agent for electricity generation, given the Coulombic efficiencies (CEs) of 17.8 ± 0.5% to 75.1 ± 0.5% for the EDTA-chelated process versus 9.6 ± 0.8% to 51.1 ± 2.7% for the NTA-chelated process in the pH range of 4.0-10.0. The Fe (III)/S(2-) ratio exhibited notable influence on the electricity generation, with the CEs improved by more than 25% as the Fe (III)/S(2-) molar ratio increased from 2.5:1 to 3.5:1. Application of this novel process in treating a H2S-containing biogas stream achieved 99% of H2S removal efficiency, 78% of sulfur recovery efficiency, and 78.6% of energy recovery efficiency, suggesting the fuel-cell-assisted chelated-iron process was effective to remove the H2S from gas streams with favorable sulfur and energy recovery efficiencies.

  18. Antidiabetic and pancreas-protective effects of zinc threoninate chelate in diabetic rats may be associated with its antioxidative stress ability.

    Science.gov (United States)

    Zhu, Kexue; Nie, Shaoping; Li, Chuan; Huang, Jianqin; Hu, Xiaobo; Li, Wenjuan; Gong, Deming; Xie, Mingyong

    2013-06-01

    Zinc exerts a wide range of important biological roles. The present study was carried out to investigate the effects of zinc threoninate chelate in blood glucose levels, lipid peroxidation, activities of antioxidant defense systems and nitrite concentration, and histology of the pancreas in diabetic rats. Wistar rats were intravenously injected with a single dose of streptozotocin to induce diabetes. Then, diabetic rats were administrated orally with zinc threoninate chelate (3, 6, and 9 mg/kg body weight) once daily for 7 weeks. Fasting blood glucose was monitored weekly. At the end of the experimental period, the diabetic rats were killed, and levels of serum insulin, malondialdehyde, and nitric oxide, activities of glutathione peroxidase, total superoxide dismutase, copper/zinc-superoxide dismutase, and nitric oxide synthase were determined; pancreas was examined histopathologically as well. Zinc threoninate chelate significantly reduced the blood glucose levels and significantly increased the serum insulin levels in diabetic rats. In addition, zinc threoninate chelate caused a significant increase in activities of antioxidant enzymes and significant decrease in nitrite concentration and malondialdehyde formation in the pancreas and serum of diabetic rats. These biochemical observations were supplemented by histopathological examination of the pancreas. These results suggested that the antidiabetic effect of zinc threoninate chelate may be related to its antioxidative stress ability in diabetic rats.

  19. Deferoxamine alleviates chronic hydrocephalus after intraventricular hemorrhage through iron chelation and Wnt1/Wnt3a inhibition.

    Science.gov (United States)

    Meng, Hui; Li, Fei; Hu, Rong; Yuan, Yikai; Gong, Guoqi; Hu, Shengli; Feng, Hua

    2015-03-30

    Post-hemorrhagic chronic hydrocephalus (PHCH) is a common complication after intraventricular hemorrhage (IVH). The mechanism of PHCH is not fully understood, and its treatment is relatively difficult. In the present study, a rat model of PHCH was used to elucidate the role of iron in the pathogenesis of PHCH. The action of deferoxamine (DFX) in IVH-induced PHCH, the expression of brain ferritin, the concentration of iron in cerebrospinal fluid (CSF), and changes in Wnt1/Wnt3a gene expression were determined. Results indicate that iron plays an important role in the occurrence of hydrocephalus after IVH. The iron chelator, DFX, can decrease the concentrations of iron and ferritin after cerebral hemorrhage and can thereby decrease the incidence of hydrocephalus. In addition, after IVH, the gene expression of Wnt1 and Wnt3a was enhanced, with protein expression also upregulated; DFX was able to suppress both gene and protein expression of Wnt1 and Wnt3a in brain tissue. This indicates that iron may be the key stimulus that activates the Wnt signaling pathway and regulates subarachnoid fibrosis after cerebral hemorrhage, and that DFX may be a candidate for preventing PHCH in patients with IVH.

  20. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    Science.gov (United States)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

  1. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; El-Beshlawy, Amal; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Habr, Dany; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Al Jefri, Abdullah

    2009-01-01

    Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20–30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1–7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw. Results: Overall, 233/237 enrolled patients completed 1 yr’s treatment. Mean baseline LIC was 18.0 ± 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr’s deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden

  2. Hematological improvement during iron-chelation therapy in myelodysplastic syndromes: the experience of the "Rete Ematologica Lombarda".

    Science.gov (United States)

    Molteni, Alfredo; Riva, Marta; Pellizzari, Annamaria; Borin, Lorenza; Freyrie, Alessandra; Freyre, Alessandra; Greco, Rosa; Ubezio, Marta; Bernardi, Massimo; Fariciotti, Alessio; Nador, Guido; Nichelatti, Michele; Ravano, Emanuele; Morra, Enrica

    2013-10-01

    To analyze the unpredicted event of hematological improvement (HI) during iron-chelation therapy (ICT), we reviewed a series of 53 myelodysplastic patients with transfusion dependency in a retrospective study involving 8 centers afferent to the "Rete Ematologica Lombarda". According to the IWG response criteria published in the year 2000, we observed erythroid responses in 19 patients (35.1%), 5 major (9.2%) and 14 minor (25.9%). In the assessable patients, platelet response was 8/13 (61%) and neutrophil response was 13/17 (76.4%). Only in patients with erythroid improvement, multilineage responses were observed. Apparently, patients with greater erythropoiesis dysfunction may take more advantage.

  3. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial

    DEFF Research Database (Denmark)

    Lee, Jong Wook; Yoon, Sung-Soo; Shen, Zhi Xiang

    2010-01-01

    The prospective 1-year Evaluation of Patients' Iron Chelation with Exjade (EPIC) study enrolled a large cohort of 116 patients with aplastic anemia; the present analyses evaluated the efficacy and safety of deferasirox in this patient population. After 1 year, median serum ferritin decreased...... neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www...

  4. Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Xi-Xun Du; Hua-Min Xu; Hong Jiang; Ning Song; Jun Wang; Jun-Xia Xie

    2012-01-01

    [Objective] Curcumin is a plant polyphenolic compound and a major component of spice turmeric (Curcuma longa).It has been reported to possess free radical-scavenging,iron-chelating,and anti-inflammatory properties in different tissues.Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro.The present study aimed to explore this neuroprotective effect in the 6-OHDAlesioned rat model of Parkinson's disease in vivo.[Methods] Rats were given intragastric curcumin for 24 days.6-OHDA lesioning was conducted on day 4 of curcumin treatment.Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection,tyrosine hydroxylase (TH)-containing neurons by immunohistochemistry,and iron-containing cells by Perls' iron staining.[Results] The dopamine content in the striatum and the number of THimmunoreactive neurons decreased after 6-OHDA treatment.Curcumin pretreatment reversed these changes.Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells,which was dramatically decreased by curcumin pretreatment.[Conclusion]The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.

  5. Iron chelation with deferasirox for the treatment of secondary hemosiderosis in pediatric oncology patients: a single-center experience.

    Science.gov (United States)

    Ktena, Yiouli P; Athanasiadou, Anastasia; Lambrou, George; Adamaki, Maria; Moschovi, Maria

    2013-08-01

    Pediatric oncology patients are often iron overloaded, due to the multiple blood transfusions necessary during the course of chemotherapy. Our aim is to report the efficacy and safety of deferasirox, an oral iron chelator, in this patient group. Deferasirox was administered to 13 children with malignancies in remission and iron overload. Ferritin, blood urea nitrogen, creatinine, transaminases, and bilirubin were recorded at 4- to 8-week intervals, and hepatic and cardiac iron overload were assessed with magnetic resonance imaging before initiation of treatment. Deferasirox was administered for an average of 6 months (SD=4.5; range, 0.3 to 18.2). Two children presented with skin rash, 1 with gastrointestinal disturbances, and 1 with fully reversible acute renal failure. The mean monthly rate of change in ferritin levels was -10.8 μg/L before initiation of treatment (95% confidence interval [CI], -19.8 to -1.8; P=0.02) and -93.6 μg/L during deferasirox treatment (95% CI, -118.1 to -69.1; PDeferasirox was effective in reducing the iron burden. The adverse effects were easily monitored and managed. Further studies are warranted to investigate the effect of deferasirox on mortality and morbidity in this population.

  6. Overview of iron overload and the new iron chelator deferasirox%铁过载概述及口服祛铁新药地拉罗司

    Institute of Scientific and Technical Information of China (English)

    刘容容

    2011-01-01

    规则输血是维持重度慢性贫血患者生命的重要治疗手段,患者长期依赖输血治疗不可避免地引起体内铁沉积增加.输血相关性铁过载可导致多脏器的损害,特别是沉积在肝脏或心脏,甚至可危及生命.作为传统的铁螯合剂,去铁酮和去铁胺因其不良反应或治疗依从性差等问题无法满足临床治疗需要.地拉罗司是一种新型的口服铁螯合剂,多个Ⅱ期或Ⅲ期试验证实其在输血依赖性患者中可获得与去铁胺相似的疗效.近期前瞻性、多中心EPIC研究也证实了其祛铁疗效,且有助于改善地中海贫血患者的心脏铁沉积.本文就铁过载的临床特征、危害性以及祛铁新药地拉罗司对比传统药物的优势做一综述.%For many patients with severe chronic anemia, regular blood transfusion is the important lifesav-ing therapy available. Long-term blood transfusions will unavoidably and invariably produce accumulation of iron (iron overload) , and thereby induced iron toxicity. Transfusional hemosiderosis, particularly in the liver or heart, can cause considerable morbidity that may be fatal eventually. Traditionally, iron chelating agents include def-eriprone and deferoxamine, but they are not the satisfied treatment choice due to their side effects or non-convenience for administration. Deferasirox, a rationally-designed oral iron chelator, is validated as defined by several phase II trials. Moreover, a pivotal phase III trial revealed that its efficacy is similar to that of deferoxamine in transfusion-dependent patients. Recently reported results from the large, prospective, multicenter EPIC study confirmed its efficacy, and in this study deferasirox was also found to be capable of removing iron from the heart in patients with p-thalassemia and myocardial hemosiderosis. This review summarized the morbidity, mortality, and clinical features of iron overload, and introduced the advantages of the new chelator deferasirox over

  7. Regulation of AhFRO1, an Fe(III)-chelate reductase of peanut, during iron deficiency stress and intercropping with maize.

    Science.gov (United States)

    Ding, Hong; Duan, Lihong; Wu, Huilan; Yang, Rongxin; Ling, Hongqing; Li, Wen-Xue; Zhang, Fusuo

    2009-07-01

    Iron deficiency-induced chlorosis in peanut during anthesis was alleviated when peanut was intercropped with maize in field and pot experiments. Iron acquisition of graminaceous plants is characterized by the synthesis and secretion of the iron-chelating phytosiderophores. Compared to the roots of monocropped maize, the roots of maize intercropped with peanut always secreted higher amounts of phytosiderophores during peanut anthesis. For non-graminaceous plants, reduction of ferric to ferrous iron on the root surface is the rate-limiting step for mobilizing iron from soil. The full-length cDNA, AhFRO1, which is encoding an Fe(III)-chelate reductase, was isolated from peanut. AhFRO1 expression in yeast conferred Fe(III)-chelate reductase activity to the cells. Consistent with its function in iron uptake, AhFRO1 was determined to be a membrane protein by transient expression analysis. AhFRO1 mRNA accumulated under iron deficiency conditions. During pre-anthesis, the Fe(III)-chelate reductase activity and the transcript levels of AhFRO1 were similar in monocropped and intercropped peanut. When the iron deficiency-induced chlorosis developed in the monocropped peanuts, both the Fe(III)-chelate reductase activity of peanut and the transcript levels of AhFRO1 were higher in intercropped than in monocropped peanuts, which is consistent with the secretion of phytosiderophores by maize roots. We conclude that AhFRO1 in peanut and phytosiderophores from maize co-operate to improve the iron nutrition of peanut when intercropped with maize.

  8. Up-regulation of hypoxia-inducible factor (HIF)-1α and HIF-target genes in cortical neurons by the novel multifunctional iron chelator anti-Alzheimer drug, M30.

    Science.gov (United States)

    Avramovich-Tirosh, Y; Bar-Am, O; Amit, T; Youdim, M B H; Weinreb, O

    2010-06-01

    Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelator, M30, possessing the neuroprotective propargylamine moiety of the anti-Parkinsonian drug, rasagiline (Azilect) and antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of our iron chelator, VK28. M30 was recently found to confer potential neuroprotective effects in vitro and in various preclinical neurodegenerative models and regulate the levels and processing of the Alzheimer's amyloid precursor protein and its toxic amyloidogenic derivative, Abeta. Here, we show that M30 activates the hypoxia-inducible factor (HIF)-1alpha signaling pathway, thus promoting HIF-1alpha mRNA and protein expression levels, as well as increasing transcription of HIF-1alpha-dependent genes, including vascular endothelial growth factor, erythropoietin, enolase-1, p21 and tyrosine hydroxylase in rat primary cortical cells. In addition, M30 also increased the expression levels of the transcripts of brain derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43). Regarding aspects of relevance to Alzheimer's disease (AD), western blotting analysis of glycogen synthase kinase- 3beta (GSK-3beta) signaling pathway revealed that M30 enhanced the levels of phospho-AKT (Ser473) and phospho- GSK-3beta (Ser9) and attenuated Tau phosphorylation. M30 was also shown to protect cultured cortical neurons against Abeta(25-35) toxicity. All these multimodal pharmacological activities of M30 might be beneficial for its potent efficacy in the prevention and treatment of neurodegenerative conditions, such as Parkinson's disease and AD in which oxidative stress and iron-mediated toxicity are involved.

  9. Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

    Directory of Open Access Journals (Sweden)

    Harpreet Kochhar

    2015-01-01

    Full Text Available Background. Hematologic improvement (HI occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT but there is little information on transfusion status after stopping chelation. Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient’s course in detail and review the literature on HI with chelation. Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

  10. Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation

    Science.gov (United States)

    Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya

    2017-01-01

    Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

  11. Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

    Science.gov (United States)

    Taher, Ali T; Cappellini, M Domenica; Aydinok, Yesim; Porter, John B; Karakas, Zeynep; Viprakasit, Vip; Siritanaratkul, Noppadol; Kattamis, Antonis; Wang, Candace; Zhu, Zewen; Joaquin, Victor; Uwamahoro, Marie José; Lai, Yong-Rong

    2016-03-01

    Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.

  12. Bipyridine, an iron chelator, does not lessen intracerebral iron-induced damage or improve outcome after intracerebral hemorrhagic stroke in rats.

    Science.gov (United States)

    Caliaperumal, Jayalakshmi; Wowk, Shannon; Jones, Sarah; Ma, Yonglie; Colbourne, Frederick

    2013-12-01

    Iron chelators, such as the intracellular ferrous chelator 2,2'-bipyridine, are a potential means of ameliorating iron-induced injury after intracerebral hemorrhage (ICH). We evaluated bipyridine against the collagenase and whole-blood ICH models and a simplified model of iron-induced damage involving a striatal injection of FeCl2 in adult rats. First, we assessed whether bipyridine (25 mg/kg beginning 12 h post-ICH and every 12 h for 3 days) would attenuate non-heme iron levels in the brain and lessen behavioral impairments (neurological deficit scale, corner turn test, and horizontal ladder) 7 days after collagenase-induced ICH. Second, we evaluated bipyridine (20 mg/kg beginning 6 h post-ICH and then every 24 h) on edema 3 days after collagenase infusion. Body temperature was continually recorded in a subset of these rats beginning 24 h prior to ICH until euthanasia. Third, bipyridine was administered (as per experiment 2) after whole-blood infusion to examine tissue loss, neuronal degeneration, and behavioral impairments at 7 days post-stroke, as well as body temperature for 3 days post-stroke. Finally, we evaluated whether bipyridine (25 mg/kg given 2 h prior to surgery and then every 12 h for 3 days) lessens tissue loss, neuronal death, and behavioral deficits after striatal FeCl2 injection. Bipyridine caused a significant hypothermic effect (maximum drop to 34.6 °C for 2-5 h after each injection) in both ICH models; however, in all experiments bipyridine-treated rats were indistinguishable from vehicle controls on all other measures (e.g., tissue loss, behavioral impairments, etc.). These results do not support the use of bipyridine against ICH.

  13. Comparison of cardiac dysfunction in thalassemia major patients using deferoxamine or deferiprone as an iron-chelating agent

    Directory of Open Access Journals (Sweden)

    Rosalina Josep

    2012-09-01

    Full Text Available Background In Thalassemia major (TM patients, major mortality is due to cardiac hemosiderosis. Several types of iron chelating agent available recently are given to overcome this problem Objective To compare cardiac dysfunction in thalassemia major patients who used subcutaneous deferoxamine (DFO to those who used oral deferiprone (DFP as an iron-chelating agent Methods This cross-sectional study was held at the Thalassemia Center, Departemen of Child Health-Cipto Mangunkusumo Hospital (DCH-CMH, Jakarta. We included TM patients aged 10-18 years with a mean pre-transfused hemoglobin level of >7g/dL in the prior year, and who had used DFO or DFP for at least 1 year with good compliance, at astandard dose of DFO at 40-60 mg/kg/day for 5 days a week or DFP at 50-100 mg/kg/day We excluded TM patients with congenital heart disease or overt heart failure. Trans-thoracal echocardiography was performed at the Integrated Cardiac Service, CMH by a pediatric cardiologist using the conventional method and tissue Doppler imaging (TDI consecutively, and within 2 weeks of the subject’s receiving a packed red blood cell (PRBC transfusion. The 57 TM subjects consisted of 19 DFO users and 38 DFP users. Results In our subjects, diastolic dysfunction was more commonly seen than systolic dysfunction, especially moderate diastolic dysfunction. In the DFO group, diastolic dysfunction only was detected in 3/19 subjects, systolic dysfuntion only in 1/19 subjects, and both diastolic and systolic dysfuntion in 15-19 subjects. None of the DFO users had normal cardiac function. In the DFP group, diastolic dysfunction only was seen in 6/38 subjects, and both diastolic and systolic dysfunction in 30/38 subjrcts, while 2/38 subjects had normal cardiac function. Conclusion Diastolic and/or systolic dysfunction was detected in the majority of subjects, but with preserved global cardiac function. We found that cardiac dysfunction was not significantly different in the two iron

  14. Clinical management of gastrointestinal disturbances in patients with myelodysplastic syndromes receiving iron chelation treatment with deferasirox

    NARCIS (Netherlands)

    Nolte, F.; Angelucci, E.; Beris, P.; Macwhannell, A.; Selleslag, D.; Schumann, C.; Xicoy, B.; Almeida, A.; Guerci-Bresler, A.; Sliwa, T.; Muus, P.; Porter, J.; Hofmann, W.K.

    2011-01-01

    Myelodysplastic syndromes are characterized by ineffective hematopoiesis resulting in peripheral cytopenias. The majority of patients is dependent on regular transfusions of packed red blood cells leading to a secondary iron overload which might result in organ damage. Therefore, sufficient iron che

  15. Ulcerated hemosiderinic dyschromia and iron deposits within lower limbs treated with a topical application of biological chelator

    Directory of Open Access Journals (Sweden)

    Eugenio Brizzio

    2012-12-01

    Full Text Available The ulcerative haemosiderinic dyschromia of chronic venous insufficiency is difficult to heal and presents a high accumulation of iron. Lactoferrin, a potent natural iron chelator, could help to scar this ulcerative haemosi - derinic dyschromia. The objective of this study was to determine whether the topical application of a liposomal gel with Lactoferrin favors scarring/degradation of the brown colored spot typical of ulcerative haemosiderinic dyschromia. Nine patients with severe chronic venous insufficiency and ulcerative haemosiderinic dyschromia (CEAP-C6, with a natural evolution of over 12 months, were included in the study. Hemo chromatosis gene mutations were investigated. The levels of serum ferritin, transferrin saturation and blood cell counts were analyzed. The presence of hemosiderin was investigated through periulcerous and ulcer fundus biopsies carried out at baseline and 30 days after treatment with Lactoferrin. The severity of the injuries (CEAP classification was evaluated at the beginning of and throughout the whole 3-month treatment period. No patient had received compression treatment during the three months previous to this therapy. Significant improvement in these injuries, with a reduction in the dimensions of the brown spot (9 of 9 at Day 90, and complete scarring with a closure time ranging from 15 to 180 days (7 of 9 were observed. The use of topical lactoferrin is a non-invasive therapeutic tool that favors clearance of hemosiderinic dyschromia and scarring of the ulcer. The success of this study was not influenced either by the hemochromatosis genetics or the iron metabolism profile observed.

  16. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo

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    Jehn-Chuan Lee

    2016-08-01

    Full Text Available Oral squamous cell carcinoma (OSCC is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO, and deferasirox all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

  17. Profound morphological changes in the erythrocytes and fibrin networks of patients with hemochromatosis or with hyperferritinemia, and their normalization by iron chelators and other agents.

    Directory of Open Access Journals (Sweden)

    Etheresia Pretorius

    Full Text Available It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH, as well as some who displayed hyperferritinemia (HF. Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators. These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded ('free' iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise.

  18. EFFICACY AND SAFETY OF DEFERASIROX WHEN COMPARED TO D EFERIPRONE AS ORAL IRON CHELATING AGENT : A RANDOMIZED CONTROL TRIAL

    Directory of Open Access Journals (Sweden)

    Sanjeeva

    2015-03-01

    Full Text Available BACKGROUND : Thalassemia is one of the most common inherited hemoglobinopathy seen in southern India. With regular blood transfusion, these children live longer but associated morbidity due to iron overload impairs the quality of life. We studied the efficacy and safety of new oral iron chelator, deferasirox, compared with deferiprone which was used for long time. MATERIAL AND METHODS : We cond ucted a prospective randomised control study, between January 2011 to June 2012 at thalassemia day care centre of Indira Gandhi I nstitute of C hild H ealth, Bengaluru. The children who were diagnosed as Thalassemia and receiving regular blood transfusion wit h serum ferritin levels more than 1000ng/ml and not receiving any chelation therapy were included in the study. These children were randomly divided into two groups as group 1 and group 2 by computer generated randomization. The children included in g roup 1 received Deferasirox and group 2 received Deferiprone as chelation therapy. The dosage of deferasirox was 20mg/kg/day once daily and that of deferiprone 75 mg/kg/day in three divided daily doses. The primary study outcome was to measure and compare the d ecrease in serum ferritin levels between the two study groups. The secondary outcome measures were to compare the side effect profiles among the two groups. RESULTS : We included 41 thalessemic children and 19 of them were included in group 1 (Deferasirox and 22 children in Group 2 (Deferiprone. At the end of study period of 18 months three children in group II discontinued therapy due to side effects, hence the remaining 19 were available for final analysis in group 2 whereas no drop outs in the group 1. During the study period, the serum ferritin decreased from 3261±2613ng/dl to 1586±766 ng/dl in group 1 as compared in group 2 from 4109±3153 ng/dl to 1743±1138 ng/dl (fig 2. This was also not statistically significant. In group 2, 68% of the children expe rienced adverse effect as compared

  19. 乳猪小肽螯合铁的补铁效果%The Effect of Small Peptide Chelated Iron in Suckling Pigs

    Institute of Scientific and Technical Information of China (English)

    李永富; 施用晖; 喻涛

    2001-01-01

    采用小肽螯合铁作为补铁剂,妊娠和泌乳母猪以及乳猪为研究对象,测定母猪初乳铁的含量,乳猪5、10、14和21日龄的血红蛋白(Hb)以及乳猪14和21日龄的血清铁蛋白(SF)浓度.结果表明,小肽螯合铁比硫酸亚铁能够更有效地进入母乳,母猪补小肽铁可增加乳猪铁的获得,但不能解决乳猪的缺铁问题;乳猪补小肽螯合铁不但有较高的Hb水平,而且体内铁储备量高于补右旋糖苷铁,可满足乳猪铁的需要.%The experiment was conducted with sows and their piglets, tostudy the response of colostrums iron content, Hb value, serum ferrintin(SF) concentration to small peptide chelated iron in neonatal piglets. The results showed that supplement with 80 mg/kg small peptide chelated iron(as iron) in sow ration from 14 days before parturition to 21 days after parturition increased colostrum iron content of sows by 80% and the Hb level of their piglets at 14 days of age was significantly elevated when compared to FeSO4 group(P<0.05). The Hb level of piglets orally administrated with small peptide chelated iron and injected with iron dextran was optimum at 14 and 21 days of age. The SF concentration piglets orally administrated with small peptide chelated iron were significant higher than that injected with iron dextran(P<0.05). Those result suggested that small peptide chelated iron can effectively prevent piglet anemia.

  20. Role of iron metabolism genetic determinants in response to chelation therapy in a cohort of β-thalassemia and sickle cell syndromes Italian patients

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2014-09-01

    Full Text Available In patients with β-thalassemia and sickle cell syndromes there is an important secondary iron overload due to regular blood transfusions and increased duodenal iron absorption. As in genetic hemochromatosis, also the secondary iron storage leads to tissue injury that involves all the major organs: liver, heart, kidney, endocrine glands. At present, in patients with β-thalassemia and sickle cell syndrome, iron chelation therapy is widely used for the treatment of secondary hemochromatosis, to limit the toxic effects of iron overload. In order to maintain the correct homeostasis, several genes are involved in the metabolic pathways of iron, including HFE, FPN (ferroportin and TF (transferrin. In this study we analyzed the genes HFE, FPN and TF, to assess their possible effects on response to therapy with deferasirox and deferiprone, either as monotherapy or in combination therapy in a cohort of patients with β-thalassemia and sickle cell syndromes.

  1. Effects of feed supplementation with glycine chelate and iron sulfate on selected parameters of cell-mediated immune response in broiler chickens.

    Science.gov (United States)

    Jarosz, Łukasz; Kwiecień, Małgorzata; Marek, Agnieszka; Grądzki, Zbigniew; Winiarska-Mieczan, Anna; Kalinowski, Marcin; Laskowska, Ewa

    2016-08-01

    Because little is known about the impact of chelated (Fe-Gly, Fe-Gly+F) and inorganic (FeSO4, FeSO4+F) iron products on immune response parameters in broiler chickens, the objective of the study was to determine the effects of inorganic and organic forms of iron on selected parameters of the cell-mediated immune response in broiler chickens by assessing the percentage of CD3(+)CD4(+), CD3(+)CD8(+), CD25(+), and MHC Class II lymphocytes, as well as the CD4(+)/CD8(+) ratio and IL-2 concentration in the peripheral blood. The experiments were conducted using 50day-old Ross 308 roosters. The test material was peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. The results obtained indicate that the use of iron chelates in the diet of broiler chickens may stimulate cellular defense mechanisms. As a result of the experiment an increase was observed in the percentage of Th1, mainly T CD4(+) and T CD8(+). It was also noted that application of chelated iron can increase production of T CD8(+) cytotoxic cells and IL-2, which promotes the body's natural response to developing inflammation. There were no changes in T CD4(+), T CD8(+), T CD25(+) or MHC II lymphocyte subpopulations in the chickens following application of the inorganic form of iron.

  2. Impact of two iron(III) chelators on the iron, cadmium, lead and nickel accumulation in poplar grown under heavy metal stress in hydroponics.

    Science.gov (United States)

    Mihucz, Victor G; Csog, Árpád; Fodor, Ferenc; Tatár, Enikő; Szoboszlai, Norbert; Silaghi-Dumitrescu, Luminiţa; Záray, Gyula

    2012-04-15

    Poplar (Populus jacquemontiana var. glauca cv. Kopeczkii) was grown in hydroponics containing 10 μM Cd(II), Ni(II) or Pb(II), and Fe as Fe(III) EDTA or Fe(III) citrate in identical concentrations. The present study was designed to compare the accumulation and distribution of Fe, Cd, Ni and Pb within the different plant compartments. Generally, Fe and heavy-metal accumulation were higher by factor 2-7 and 1.6-3.3, respectively, when Fe(III) citrate was used. Iron transport towards the shoot depended on the Fe(III) chelate and, generally, on the heavy metal used. Lead was accumulated only in the root. The amounts of Fe and heavy metals accumulated by poplar were very similar to those of cucumber grown in an identical way, indicating strong Fe uptake regulation of these two Strategy I plants: a cultivar and a woody plant. The Strategy I Fe uptake mechanism (i.e. reducing Fe(III) followed by Fe(II) uptake), together with the Fe(III) chelate form in the nutrient solution had significant effects on Fe and heavy metal uptake. Poplar appears to show phytoremediation potential for Cd and Ni, as their transport towards the shoot was characterized by 51-54% and 26-48% depending on the Fe(III) supply in the nutrient solution.

  3. Preservation of glutamic acid-iron chelate into montmorillonite to efficiently degrade Reactive Blue 19 in a Fenton system under sunlight irradiation at neutral pH

    Science.gov (United States)

    Huang, Zhujian; Wu, Pingxiao; Gong, Beini; Yang, Shanshan; Li, Hailing; Zhu, Ziao; Cui, Lihua

    2016-05-01

    To further enhance the visible light responsive property and the chemical stability of Fe/clay mineral catalysts, glutamic acid-iron chelate intercalated montmorillonite (G-Fe-Mt) was developed. The physiochemical properties of G-Fe-Mt were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (DRS), etc. The results showed that glutamic acid-iron chelates were successfully intercalated into the gallery of montmorillonite and the intercalated glutamic acid-iron chelate molecules were well preserved. The product G-Fe-Mt displayed excellent catalytic performance in heterogeneous photo-Fenton reaction under sunlight irradiation at acidic and neutral pH values. The chelation and the visible light responsiveness of glutamic acid produce a synergistic effect leading to greatly enhanced sunlight-Fenton reaction catalyzed by the heterogeneous G-Fe-Mt under neutral pH. G-Fe-Mt is a promising catalyst for advanced oxidation processes.

  4. Overexpression of AtFRO6 in transgenic tobacco enhances ferric chelate reductase activity in leaves and increases tolerance to iron-deficiency chlorosis.

    Science.gov (United States)

    Li, Li-Ya; Cai, Qiu-Yi; Yu, Dian-Si; Guo, Chang-Hong

    2011-08-01

    The Arabidopsis gene FRO6(AtFRO6) encodes ferric chelate reductase and highly expressed in green tissues of plants. We have expressed the gene AtFRO6 under the control of a 35S promoter in transgenic tobacco plants. High-level expression of AtFRO6 in transgenic plants was confirmed by northern blot analysis. Ferric reductase activity in leaves of transgenic plants grown under iron-sufficient or iron-deficient conditions is 2.13 and 1.26 fold higher than in control plants respectively. The enhanced ferric reductase activity led to increased concentrations of ferrous iron and chlorophyll, and reduced the iron deficiency chlorosis in the transgenic plants, compared to the control plants. In roots, the concentration of ferrous iron and ferric reductase activity were not significantly different in the transgenic plants compared to the control plants. These results suggest that FRO6 functions as a ferric chelate reductase for iron uptake by leaf cells, and overexpression of AtFRO6 in transgenic plants can reduce iron deficiency chlorosis.

  5. Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1)in longterm iron loading β-thalassemic mice

    Institute of Scientific and Technical Information of China (English)

    Kanokwan; Kulprachakarn; Nittaya; Chansiw; Kanjana; Pangjit; Chada; Phisalaphong; Suthat; Fucharoen; Robert; C.Hider; Sineenart; Santitherakul; Somdet; Srichairatanakool

    2014-01-01

    Objective:To evaluate the iron—chelating properties and free—radical scavenging activities of1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methyIpyridin—4-one(CM1) treatment in chronic iron-loaded β-thalassemic(BKO) mice.Methods:The BKO mice were fed with a ferrocene-rich diet and were orally administered with CM1|50 mg/(kg·day)| for 6 months.Blood levels of non-transferrin hound iron,labile plasma iron.ferritin(Ft) and malondialdehyde were determined.Results:The BKO mice were fed with an iron diet for 8 months which resulted in iron overload.Interestingly,the mice showed a decrease in the non—transferrin bound iron,labile plasma iron and malondialdehyde levels,but not the Ft levels after continuous CM1 treatment.Conclusions:CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β—thalassemic mice.

  6. Structural and Antioxidant Properties of Compounds Obtained from Fe2+ Chelation by Juglone and Two of Its Derivatives: DFT, QTAIM, and NBO Studies

    Science.gov (United States)

    Tamafo Fouegue, Aymard Didier; Bikélé Mama, Désiré; Nkungli, Nyiang Kennet; Younang, Elie

    2016-01-01

    The chelating ability of juglone and two of its derivatives towards Fe2+ion and the antioxidant activity (AOA) of the resulting chelates and complexes (in the presence of H2O and CH3OH as ligands) in gas phase is reported via bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, proton affinity, and electron transfer enthalpy. The DFT/B3LYP level of theory associated with the 6-31+G(d,p) and 6-31G(d) Pople-style basis sets on the atoms of the ligands and the central Fe(II), respectively, was used. Negative chelation free energies obtained revealed that juglone derivatives possessing the O-H substituent (L2) have the greatest ability to chelate Fe2+ ion. Apart from 1B, thermodynamic descriptors of the AOA showed that the direct hydrogen atom transfer is the preferred mechanism of the studied molecules. NBO analysis showed that the Fe-ligand bonds are all formed through metal to ligand charge transfer. QTAIM studies revealed that among all the Fe-ligand bonds, the O1-Fe bond of 1A is purely covalent. The aforementioned results show that the ligands can be used to fight against Fe(II) toxicity, thus preserving human health, and fight against the deterioration of industrial products. In addition, most of the complexes studied have shown a better AOA than their corresponding ligands.

  7. Chelation in Metal Intoxication

    Directory of Open Access Journals (Sweden)

    Swaran J.S. Flora

    2010-06-01

    Full Text Available Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications.

  8. Synthesis, physicochemical characterization, and biological evaluation of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones: novel iron chelators with enhanced pFe(3+) values.

    Science.gov (United States)

    Liu, Z D; Khodr, H H; Liu, D Y; Lu, S L; Hider, R C

    1999-11-18

    The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe(3+) values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxymethyl substituent, particularly in the cases of 1-ethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.5) where an enhancement on pFe(3+) values in the region of two orders of magnitude is observed, as compared with Deferiprone (1, 2-dimethyl-3-hydroxypyridin-4-one) (pFe(3+) = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [(59)Fe]ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe(3+) values show great promise in their ability to remove iron under in vivo conditions.

  9. Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation

    Directory of Open Access Journals (Sweden)

    Natalia Kitsati

    2016-12-01

    Full Text Available Although it is known that Mediterranean diet plays an important role in maintaining human health, the underlying molecular mechanisms remain largely unknown. The aim of this investigation was to elucidate the potential role of ortho-dihydroxy group containing natural compounds in H2O2-induced DNA damage and apoptosis. For this purpose, the main phenolic alcohols of olive oil, namely hydroxytyrosol and tyrosol, were examined for their ability to protect cultured cells under conditions of oxidative stress. A strong correlation was observed between the ability of hydroxytyrosol to mitigate intracellular labile iron level and the protection offered against H2O2-induced DNA damage and apoptosis. On the other hand, tyrosol, which lacks the ortho-dihydroxy group, was ineffective. Moreover, hydroxytyrosol (but not tyrosol, was able to diminish the late sustained phase of H2O2-induced JNK and p38 phosphorylation. The derangement of intracellular iron homeostasis, following exposure of cells to H2O2, played pivotal role both in the induction of DNA damage and the initiation of apoptotic signaling. The presented results suggest that the protective effects exerted by ortho-dihydroxy group containing dietary compounds against oxidative stress-induced cell damage are linked to their ability to influence changes in the intracellular labile iron homeostasis.

  10. Calcium-Mediated Control of Polydopamine Film Oxidation and Iron Chelation

    Science.gov (United States)

    Klosterman, Luke; Bettinger, Christopher J.

    2016-01-01

    The facile preparation of conformal polydopamine (PDA) films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films. PDA films incubated in alkaline CaCl2 solutions exhibit accelerated oxidative evolution in a dose-dependent manner. PDA films incubated in CaCl2 solutions exhibit 53% of the oxidative charge transfer compared to pristine PDA films. Carboxylic acid groups generated from the oxidation process lower the isoelectric point of PDA films from pH = 4.0 ± 0.2 to pH = 3.1 ± 0.3. PDA films exposed to CaCl2 solutions during post-processing also enhance Fe2+/Fe3+ chelation compared to pristine PDA films. These data illustrate that the molecular heterogeneity and non-equilibrium character of as-deposited PDA films afford control over the final composition by choosing post-processing conditions, but also demands forethought into how the performance of PDA-incorporated devices may change over time in salt solutions. PMID:28025498

  11. Calcium-Mediated Control of Polydopamine Film Oxidation and Iron Chelation

    Directory of Open Access Journals (Sweden)

    Luke Klosterman

    2016-12-01

    Full Text Available The facile preparation of conformal polydopamine (PDA films on broad classes of materials has prompted extensive research into a wide variety of potential applications for PDA. The constituent molecular species in PDA exhibit diverse chemical moieties, and therefore highly variable properties of PDA-based devices may evolve with post-processing conditions. Here we report the use of redox-inactive cations for oxidative post-processing of deposited PDA films. PDA films incubated in alkaline CaCl2 solutions exhibit accelerated oxidative evolution in a dose-dependent manner. PDA films incubated in CaCl2 solutions exhibit 53% of the oxidative charge transfer compared to pristine PDA films. Carboxylic acid groups generated from the oxidation process lower the isoelectric point of PDA films from pH = 4.0 ± 0.2 to pH = 3.1 ± 0.3. PDA films exposed to CaCl2 solutions during post-processing also enhance Fe2+/Fe3+ chelation compared to pristine PDA films. These data illustrate that the molecular heterogeneity and non-equilibrium character of as-deposited PDA films afford control over the final composition by choosing post-processing conditions, but also demands forethought into how the performance of PDA-incorporated devices may change over time in salt solutions.

  12. Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with nontransfusion-dependent thalassemia syndromes

    Directory of Open Access Journals (Sweden)

    Taher AT

    2016-12-01

    Full Text Available Ali T Taher,1 John B Porter,2 Antonis Kattamis,3 Vip Viprakasit,4 M Domenica Cappellini51Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; 2Department of Haematology, University College London, London, UK; 3First Department of Pediatrics, University of Athens, Athens, Greece; 4Department of Pediatrics and Thalassemia Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 5Department of Internal Medicine, Università di Milano, Ca Granda Foundation IRCCS, Milan, ItalyAs the scientific steering committee for THALASSA (an assessment of Exjade in nontransfusion-dependent thalassemia [NTDT], we read with interest the review by Kontoghiorghe and Kontoghiorghes entitled “Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes” published in January 2016.1 While this review provides a detailed overview of available iron chelators for the treatment of NTDT patients, there remain some factual inaccuracies and misrepresentations of data related to deferasirox. Therefore, we believe that the current article may be misleading to readers of Drug Design, Development and Therapy.Author’s replyGeorge J KontoghiorghesPostgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol, CyprusThere are many murky areas and marketing, legal, ethical, and other conflicts in the pharmaceutical industry, some of which involve physicians and academics. These activities and related ethical issues affect the safety and treatment of millions of patients.1–11 Irregular and sometimes illegal activities for new patented drugs carried out by pharmaceutical companies, such as secrecy agreements with academics/academic institutions, can lead to biased reporting of the results of clinical trials and cover ups or underreporting of toxic side effects, as well as doctor’s bribes

  13. Age-associated iron accumulation in bone: implications for postmenopausal osteoporosis and a new target for prevention and treatment by chelation.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Kenner, Gerry H; Miller, Scott C

    2006-06-01

    Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency). To further investigate whether the increased iron level plays a causal role in the onset of bone loss, we treated OVX rats with an orally active and bone targeted chelator that prevented iron accumulation in their skeletal tissues. The results showed that this treatment mitigated the loss of bone mass and the deterioration of bone micro-architecture. We also found that one possible mechanism of the protective action of iron chelation was to significantly reduce bone resorption. Thus, these findings provide a novel target and a potentially useful therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis and perhaps other age-related diseases.

  14. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  15. The urinary antibiotic 5-nitro-8-hydroxyquinoline (Nitroxoline) reduces the formation and induces the dispersal of Pseudomonas aeruginosa biofilms by chelation of iron and zinc.

    Science.gov (United States)

    Sobke, A; Klinger, M; Hermann, B; Sachse, S; Nietzsche, S; Makarewicz, O; Keller, P M; Pfister, W; Straube, E

    2012-11-01

    Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity.

  16. Two cell cycle blocks caused by iron chelation of neuroblastoma cells: separating cell cycle events associated with each block.

    Science.gov (United States)

    Siriwardana, Gamini; Seligman, Paul A

    2013-12-01

    Studies have presented evidence that besides the well described S phase block, treatment of cancer cell lines with the iron chelator deferrioxamine (DFO) also results in an earlier block in G1 phase. In this article, measurements of cell cycle regulatory proteins define this block at a very specific point in G1. DFO treatment results in markedly decreased cyclin A protein levels. Cyclin E levels that accumulate in early to mid-G1 are increased in cells treated with DFO as compared to the resting cells. The DFO S phase block is shown after cells are arrested at G1/S by (aphidicolin) then released into DFO. The same S phase block occurs with DFO treatment of a neuroblastoma cell line relatively resistant to the G1 DFO block. These experiments clearly differentiate the S phase DFO block from the earlier block pinpointed to a point in mid-G1, before G1/S when cyclin E protein increases but before increased cyclin A synthesis. Apoptosis was observed in cells inhibited by DFO at both cell cycle arrest points.

  17. Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2012-01-01

    Conclusions: Maltol with the highest test dose was capable to protect against experimentally induced colitis. Kojic acid and vitamin E were not effective in this animal model of colon inflammation. More detailed studies are warranted to explore the mechanisms involved in anti-colitic property of maltol and to explain ineffectiveness of kojic acid and vitamin E.

  18. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up.

    Science.gov (United States)

    Cappellini, M Domenica; Bejaoui, Mohamed; Agaoglu, Leyla; Canatan, Duran; Capra, Marcello; Cohen, Alan; Drelichman, Guillermo; Economou, Marina; Fattoum, Slaheddine; Kattamis, Antonis; Kilinc, Yurdanur; Perrotta, Silverio; Piga, Antonio; Porter, John B; Griffel, Louis; Dong, Victor; Clark, Joan; Aydinok, Yesim

    2011-07-28

    Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.

  19. Hexadentate hydroxypyridonate iron chelators based on TREN-Me-3,2-HOPO: variation of cap size.

    Science.gov (United States)

    Xu, Jide; O'Sullivan, Brendon; Raymond, Kenneth N

    2002-12-16

    TREN-Me-3,2-HOPO, TR322-Me-3,2-HOPO, TR332-Me-3,2-HOPO, and TRPN-Me-3,2-HOPO correspond to stepwise replacement of ethylene by propylene bridges. A series of tripodal, hexadentate hydroxypyridinone ligands are reported. These incorporate 1-methyl-3,2-hydroxypyridinone (Me-3,2-HOPO) bidentate chelating units for metal binding. They are varied by systematic enlargement of the capping scaffold which connects the binding units. The series of ligands and their iron complexes are reported. Single crystal X-ray structures are reported for the ferric complexes of all four tripodal ligands: FeTREN-Me-3,2-HOPO.0.375C(4)H(10)O.0.5CH(2)Cl(2) [P2(1)/n (No. 14), Z = 8, a = 20.478(3) A, b = 12.353(2) A, c = 27.360(3) A; beta = 91.60(1) degrees ]; FeTR322-Me-3,2-HOPO.CHCl(3).0.5C(6)H(14).CH(3)OH.0.5H(2)O [P2(1)/n (No. 14), Z = 4, a = 12.520(3) A, b = 22.577(5) A, c = 16.525(3) A; beta = 111.37(3) degrees ]; FeTR332-Me-3,2-HOPO.3.5CH(3)OH [C2/c (No. 15), Z = 8, a = 13.5294(3) A, b = 19.7831(4) A, c = 27.2439(4) A; beta = 101.15(3) degrees ]; FeTRPN-Me-3,2-HOPO.C(3)H(7)NO.2C(4)H(10)O [P1 (No. 2), Z = 2, a = 11.4891(2) A, b = 12.3583(2) A, c = 15.0473(2) A; alpha = 86.857(1) degrees, beta = 88.414(1) degrees, gamma = 70.124(1) degrees ]. The structures show the importance of intermolecular hydrogen bonds and the effect of cap enlargement to the stability and geometry of the metal complexes throughout the series. All protonation and iron complex formation constants have been determined from solution thermodynamic studies. The TREN-capped derivative is the most acidic, with a cumulative protonation constant, log beta(014), of 25.95. Corresponding values of 26.35, 26.93, and 27.53 were obtained for the TR322, TR332, and TRPN derivatives, respectively. The protonation constants and NMR spectroscopic data are interpreted as being due to the influence of specific hydrogen-bond interactions. The incremental enlargement of ligand size results in a decrease in iron-chelate stability, as

  20. Antioxidant properties of isolated isorhamnetin from the sea buckthorn marc.

    Science.gov (United States)

    Pengfei, Liu; Tiansheng, Deng; Xianglin, Hou; Jianguo, Wang

    2009-06-01

    In the present study, the process of separation and purification of isohamnetin from marc of sea buckthorn was obtained. The antioxidant properties of the pure isolated isorhamnetin were evaluated by the scavenging of the diphenylpicrylhydrazyl radical (DPPH), iron (III) to iron (II)-reducing, and iron-chelating assays. High purity isorhamnetin (92.1%) was obtained and the results of antioxidant assays showed that isorhamnetin performed significantly compared with ascorbic acid and BHT, and the linear correlations were good in these assays. In conclusion, isorhamnetin may have potential as a natural antioxidant to alternate synthetic substances as food additive with its antioxidant activity.

  1. Optimization of High-Gravity Chelated Iron Process for Removing H2S Based on Response Surface Methodology

    Institute of Scientific and Technical Information of China (English)

    Luo Ying; Zhang Zhongzhe; Qi Jibing; Li Gang; Qi Guisheng; Liu Youzhi

    2015-01-01

    By using a mixture of N2 and H2S as the simulated APG (associated petroleum gas), the desulfurization experi-ment was performed in a cross-lfow rotating packed bed (RPB) based on the chelated iron oxidation-reduction method. In order to determine the operating conditions of the system, the effects of the concentration of Fe3+ions (ranging from 0.1 to 0.2 mol/L), the liquid-gas volume ratio (ranging from 15 to 25 L/m3) and the high gravity factor (ranging from 36 to 126) on the removal of H2S were studied by means of the Box-Behnken design (BBD) under response surface methodology (RSM). The overall results have demonstrated that the BBD with an experimental design can be used effectively in the optimization of the desulfurization process. The optimal conditions based on both individualized and combined responses (at a Fe3+ion concentration of 0.16 mol/L, a liquid-gas volume ratio of 20.67 L/m3 and a high gravity factor of 87) were found. Under this optimum condition, the desulfurization efifciency could reach 98.81%when the H2S concentration was 7 g/m3 in APG. In this work, the sulfur product was analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and the energy dispersive X-ray spectrometer (EDX). The results of analysis show that the sulfur is made of the high-purity orthorhombic crystals, which are advantageous to environmental conservation.

  2. [The antioxidant effects of emoxipin in patients with iron-deficiency anemia].

    Science.gov (United States)

    Shved, M I; Palamar, T O

    1995-01-01

    A total of 78 female patients of child-bearing age with iron deficiency anemia (IDA) of varying genesis and degree of severity were examined for effectiveness of a synthetic antioxidant emoxypine in a combined treatment of IDA. IDA was found to be associated with activation of lipid peroxidation processes (LPO) and decrement in antioxidant defence of the body. Conventional antianemic therapy does not lead to normalization of parameters characterizing LPO. Incorporation into a complex therapy of a synthetic antioxidant emoxypine reduces activity of free-radical oxidation of lipids, which fact prevents the pathological process from progressing and leads to more rapid and lasting clinical remission.

  3. Chemical evaluation of HBED/Fe(3+) and the novel HJB/Fe(3+) chelates as fertilizers to alleviate iron chlorosis.

    Science.gov (United States)

    López-Rayo, Sandra; Hernández, Diana; Lucena, Juan J

    2009-09-23

    Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenylacetic) acid (o,o-EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soil. A new chelating agent, HJB (N,N'-bis(2-hydroxy-5-methylphenyl)ethylendiamine-N,N'-diacetic acid) may be an alternative to o,o-EDDHA since its synthesis yields a purer product, but its chemical behavior and efficiency as chlorosis corrector should be evaluated. In this research, a known analogous HBED (N,N'-bis(2-hydroxyphenyl)ethylendiamine-N,N'-diacetic acid) has also been considered. First, an ion-pair high performance liquid chromatography (HPLC) method has been tested for the HJB/Fe(3+) and HBED/Fe(3+) determination. The ability of HJB and HBED to maintain Fe in solution has been compared with respect to o,o-EDDHA. Theoretical modelization for HBED and HJB in agronomic conditions has been done after the determination of the protonation and Ca(II), Mg(II), Fe(III), and Cu(II) stability constants for HJB. Also, batch interaction experiments with soils and soil materials have been conducted. According to our results, HJB/Fe(3+) and HBED/Fe(3+) present high stability, even when competing cations (Cu(2+), Ca(2+)) are present, and have low reactivity with soils and soil components. The chelating agent HJB dissolves a higher amount of Fe than o,o-EDDHA, and it seems as effective as o,o-EDDHA in keeping Fe in solution. These results indicate that these chelates may be very efficient products to correct Fe chlorosis, and additional plant experiments should demonstrate plants' ability to assimilate Fe from HJB/Fe(3+) and HBED/Fe(3+).

  4. The oral iron chelator deferasirox inhibits NF-κB mediated gene expression without impacting on proximal activation: implications for myelodysplasia and aplastic anaemia.

    Science.gov (United States)

    Banerjee, Ashish; Mifsud, Nicole A; Bird, Robert; Forsyth, Cecily; Szer, Jeff; Tam, Constantine; Kellner, Sybil; Grigg, Andrew; Motum, Penelope; Bentley, Mark; Opat, Stephen; Grigoriadis, George

    2015-02-01

    The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.

  5. Rat liver antioxidant response to iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Saporito-Magriñá, Christian; Semprine, Jimena; Torti, Horacio; Ferrarotti, Nidia; Castro-Parodi, Mauricio; Damiano, Alicia; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    The rat liver antioxidant response to Fe and Cu overloads (0-60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110-124μgFe/g and 40-50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30-92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8-8.5h and Mn-SOD: t1/2: 8.5-8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.

  6. Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate.

    Science.gov (United States)

    Ferrari, Paola; Nicolini, Andrea; Manca, Maria Laura; Rossi, Giuseppe; Anselmi, Loretta; Conte, Massimo; Carpi, Angelo; Bonino, Ferruccio

    2012-09-01

    In cancer patients mild-moderate non-chemotherapy-induced iron deficiency anemia (IDA) is usually treated with oral iron salts, mostly ferrous sulfate. In this study, we compare efficacy and toxicity of oral ferrous bisglycinate chelate and ferrous sulfate in cancer patients with mild IDA. Twenty-four patients operated on for solid tumors (10 breast, 12 colorectal, 2 gastric), aged 61±10 years (range 45-75), with non-chemotherapy-induced hemoglobin (Hb) values between 10 and 12 g/dL and ferritin lower than 30 ng/mL were randomized to receive oral ferrous bisglycinate chelate, 28 mg per day for 20 days, and then 14 mg per day for 40 days (12 patients) (A group) or oral ferrous sulphate, 105 mg per day for 60 days (12 patients) (B group). Values of hemoglobin and ferritin obtained at diagnosis, 1 and 2 months from the beginning of treatment were compared. Adverse events (AEs) related to the two treatments were recorded. In the 12 patients treated with ferrous bisglycinate chelate, basal hemoglobin and ferritin values (mean±SD) were 11.6±0.8 g/dL and 16.1±8.0 ng/mL. After 2 months of treatment, they were 13.0±1.4 g/dL and 33.8±22.0 ng/mL, respectively (P=0.0003 and P=0.020). In the group treated with ferrous sulphate, hemoglobin and ferritin mean values were 11.3±0.6 g/dL and 19.0±6.4 ng/mL basally, and 12.7±0.70 g/dL and 40.8±28.1 ng/mL (P<0.0001 and P=0.017) after 2 months of treatment. AEs occurred in six cases. In all these six cases, two (17%) treated with ferrous bisglycinate chelate and four (33%) with ferrous sulphate, toxicity was grade 1. In conclusion, these data suggest that ferrous bisglycinate chelate has similar efficacy and likely lower GI toxicity than ferrous sulphate given at the conventional dose of 105 mg per day for the same time.

  7. Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure.

    Science.gov (United States)

    Xing, Wei; Li, Dunhai; Liu, Guihua

    2010-01-01

    Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure were investigated in the study. Results showed that iron accumulation in E. nuttallii was concentration dependent. Growth of E. nuttallii was promoted by low iron concentration (1-10 mg L(-1) [Fe(3+)]), but growth inhibition was observed when iron concentration beyond 10 mg L(-1). The synthesis of protein and pigments increased within 1-10 mg L(-1) [Fe(3+)] range. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-S-transferase (GST) were up to maximal values at 10 mg L(-1) [Fe(3+)]. High iron concentration inhibited the synthesis of protein and pigments as well as activities of antioxidative enzymes, and accelerated degradation of pigment and production of ROS. Low iron concentration had no significant influences on PSII maximal quantum yield, activity of PSII and relative electron transport rate though PSII. Malondialdehyde (MDA) and proline concentrations were highest at 100 and 1 mg L(-1) [Fe(3+)], respectively.

  8. Magnetic bead-based enzyme-chromogenic substrate system for ultrasensitive colorimetric immunoassay accompanying cascade reaction for enzymatic formation of squaric acid-iron(III) chelate.

    Science.gov (United States)

    Lai, Wenqiang; Tang, Dianping; Zhuang, Junyang; Chen, Guonan; Yang, Huanghao

    2014-05-20

    This work reports on a simple and feasible colorimetric immunoassay with signal amplification for sensitive determination of prostate-specific antigen (PSA, used as a model) at an ultralow concentration by using a new enzyme-chromogenic substrate system. We discovered that glucose oxidase (GOx), the enzyme broadly used in enzyme-linked immunosorbent assay (ELISA), has the ability to stimulate in situ formation of squaric acid (SQA)-iron(III) chelate. GOx-catalyzed oxidization of glucose leads to the formation of gluconic acid and hydrogen peroxide (H2O2). The latter can catalytically oxidize iron(II) to iron(III), which can rapidly (immunoassay protocol with GOx-labeled anti-PSA detection antibody can be designed for the detection of target PSA on capture antibody-functionalized magnetic immunosensing probe, monitored by recording the color or absorbance (λ = 468 nm) of the generated SQA-iron(III) chelate. The absorbance intensity shows to be dependent on the concentration of target PSA. A linear dependence between the absorbance and target PSA concentration is obtained under optimal conditions in the range from 1.0 pg mL(-1) to 30 ng mL(-1) with a detection limit (LOD) of 0.5 pg mL(-1) (0.5 ppt) estimated at the 3Sblank level. The sensitivity displays to be 3-5 orders of magnitude better than those of most commercialized human PSA ELISA kits. In addition, the developed colorimetric immunoassay was validated by assaying 12 human serum samples, receiving in good accordance with those obtained by the commercialized PSA ELISA kit. Importantly, the SQA-based immunosensing system can be further extended for the detection of other low-abundance proteins or biomarkers by controlling the target antibody.

  9. The iron chelator, deferasirox, as a novel strategy for cancer treatment: oral activity against human lung tumor xenografts and molecular mechanism of action.

    Science.gov (United States)

    Lui, Goldie Y L; Obeidy, Peyman; Ford, Samuel J; Tselepis, Chris; Sharp, Danae M; Jansson, Patric J; Kalinowski, Danuta S; Kovacevic, Zaklina; Lovejoy, David B; Richardson, Des R

    2013-01-01

    Deferasirox is an orally effective iron (Fe) chelator currently used for the treatment of iron-overload disease and has been implemented as an alternative to the gold standard chelator, desferrioxamine (DFO). Earlier studies demonstrated that DFO exhibits anticancer activity due to its ability to deplete cancer cells of iron. In this investigation, we examined the in vitro and in vivo activity of deferasirox against cells from human solid tumors. To date, there have been no studies to investigate the effect of deferasirox on these types of tumors in vivo. Deferasirox demonstrated similar activity at inhibiting proliferation of DMS-53 lung carcinoma and SK-N-MC neuroepithelioma cell lines compared with DFO. Furthermore, deferasirox was generally similar or slightly more effective than DFO at mobilizing cellular (59)Fe and inhibiting iron uptake from human transferrin depending on the cell type. However, deferasirox potently inhibited DMS-53 xenograft growth in nude mice when given by oral gavage, with no marked alterations in normal tissue histology. To understand the antitumor activity of deferasirox, we investigated its effect on the expression of molecules that play key roles in metastasis, cell cycle control, and apoptosis. We demonstrated that deferasirox increased expression of the metastasis suppressor protein N-myc downstream-regulated gene 1 and upregulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) while decreasing cyclin D1 levels. Moreover, this agent increased the expression of apoptosis markers, including cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1. Collectively, we demonstrate that deferasirox is an orally effective antitumor agent against solid tumors.

  10. Decomplexation and subsequent reductive removal of EDTA-chelated Cu II by zero-valent iron coupled with a weak magnetic field: Performances and mechanisms.

    Science.gov (United States)

    Guan, Xiaohong; Jiang, Xiao; Qiao, Junlian; Zhou, Gongming

    2015-12-30

    The feasibility of EDTA-chelated Cu(II) (Cu(II)-EDTA) removal by zero-valent iron (Fe(0)) in the presence of a weak magnetic field (WMF) and the involved mechanisms were systematically investigated. Fe(0) combined with WMF (Fe(0)/WMF) was very effective for removing Cu(II)-EDTA at pH 4.0-6.0 with the rate constants ranging from 0.1190 min(-1) to 0.0704 min(-1). Little passivation of Fe(0) was observed during Cu(II)-EDTA removal by Fe(0)/WMF in 8 consecutive runs when 10.0 mg L(-1) Cu(II)-EDTA was dosed before the initiation of each run. The evidences presented in this study verified that Cu(II)-EDTA was removed by decomplexation followed by reduction/adsorption. In brief, Fe(II) released from Fe(0) corrosion was rapidly oxidized by oxygen to Fe(III) to chelate with EDTA and release free Cu(II), and the detached Cu(II) ions were subsequently reduced/removed by Fe(0)/Fe(II) and co-precipitated by the generated iron (hydr)-oxides. To advance the application of Fe(0)/WMF technology in real practice, a magnetic propeller agitator was designed to offer WMF inside the reactor, which could greatly improve Cu(II)-EDTA removal by Fe(0) and be easily amplified.

  11. Iron translocation in Pleurotus ostreatus basidiocarps: production, bioavailability, and antioxidant activity.

    Science.gov (United States)

    Yokota, M E; Frison, P S; Marcante, R C; Jorge, L F; Valle, J S; Dragunski, D C; Colauto, N B; Linde, G A

    2016-02-22

    Translocation of minerals from substrate to mushrooms can change the medicinal characteristics, commercial value, and biological efficiency of mushroom. In the present study, we demonstrated that addition of iron to the substrate reduces the yield of Pleurotus ostreatus mushroom. The biological efficiency of the mushroom varied from 36.53% on the unsupplemented substrate to 2.08% for the substrate with 500 mg/kg iron added. The maximum iron concentration obtained for mushroom was 478.66 mg/kg (dry basis) and the maximum solubility in vitro was 293.70 mg/kg (dry basis). Iron translocation increased the ash and protein content, reduced antioxidant activity, and enhanced the aroma and flavor characteristics of the mushroom. However mushroom has higher amounts of iron than vegetables like collard greens, it is not feasible to use mushrooms as the only dietary source of iron. The study also indicated that because of more bioaccumulation of iron in mycelium than in the mushroom, mycelium and not mushroom, could be a better alternative as a non-animal iron source.

  12. Antioxidant potential of water hyacinth (Eichornia crassipes): In vitro antioxidant activity and phenolic composition

    DEFF Research Database (Denmark)

    Surendraraj, Alagarsamy; Farvin, Sabeena; Anandan, R.

    2011-01-01

    The aims of the present study were (a) to extract and quantify the main phenolic acids and tocopherols from the petiole, leaf and flowers of Eichornia crassipes, (b) to evaluate the antioxidant capacity of the extracts in four in vitro systems (DPPH radical scavenging ability, iron chelating acti...

  13. A Young Adult with Unintentional Acute Parenteral Iron intoxication Treated with Oral Chelation: The Use of Liver Ferriscan.

    Directory of Open Access Journals (Sweden)

    Vincenzo De Sanctis

    2016-12-01

    Full Text Available Acute iron poisoning in humans has not been adequately studied. Toxicity depends on the severity of iron overload. Manifestation of acute iron poisoning, defined as a serum iron concentration >300 µg/dL (55 µmol/L within 12 hours of ingestion, by oral route include numerous symptoms which appear in progressive stages.  Systemic toxicity is expected with an ingestion of 60 mg/kg.  A 27 year old female nurse presented to hematology department with iron toxicity 1 week after self-injecting herself with 20 ampoules of IV iron (4000 mg elemental iron, 60 mg/kg. Her vital signs were stable but she had mild hepatic tenderness.

  14. Hypoxia-inducible factor prolyl hydroxylases as targets for neuroprotection by "antioxidant" metal chelators: From ferroptosis to stroke.

    Science.gov (United States)

    Speer, Rachel E; Karuppagounder, Saravanan S; Basso, Manuela; Sleiman, Sama F; Kumar, Amit; Brand, David; Smirnova, Natalya; Gazaryan, Irina; Khim, Soah J; Ratan, Rajiv R

    2013-09-01

    Neurologic conditions including stroke, Alzheimer disease, Parkinson disease, and Huntington disease are leading causes of death and long-term disability in the United States, and efforts to develop novel therapeutics for these conditions have historically had poor success in translating from bench to bedside. Hypoxia-inducible factor (HIF)-1α mediates a broad, evolutionarily conserved, endogenous adaptive program to hypoxia, and manipulation of components of the HIF pathway is neuroprotective in a number of human neurological diseases and experimental models. In this review, we discuss molecular components of one aspect of hypoxic adaptation in detail and provide perspective on which targets within this pathway seem to be ripest for preventing and repairing neurodegeneration. Further, we highlight the role of HIF prolyl hydroxylases as emerging targets for the salutary effects of metal chelators on ferroptosis in vitro as well in animal models of neurological diseases.

  15. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

    Science.gov (United States)

    Messa, Emanuela; Carturan, Sonia; Maffè, Chiara; Pautasso, Marisa; Bracco, Enrico; Roetto, Antonella; Messa, Francesca; Arruga, Francesca; Defilippi, Ilaria; Rosso, Valentina; Zanone, Chiara; Rotolo, Antonia; Greco, Elisabetta; Pellegrino, Rosa M.; Alberti, Daniele; Saglio, Giuseppe; Cilloni, Daniela

    2010-01-01

    Background Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in patients affected by myelodysplastic syndromes. Furthermore, the novel chelator deferasirox induces a similar improvement more rapidly. Nuclear factor-κB is a key regulator of many cellular processes and its impaired activity has been described in different myeloid malignancies including myelodysplastic syndromes. Design and Methods We evaluated deferasirox activity on nuclear factor-κB in myelodysplastic syndromes as a possible mechanism involved in hemoglobin improvement during in vivo treatment. Forty peripheral blood samples collected from myelodysplastic syndrome patients were incubated with 50 μM deferasirox for 18h. Results Nuclear factor-κB activity dramatically decreased in samples showing high basal activity as well as in cell lines, whereas no similar behavior was observed with other iron chelators despite a similar reduction in reactive oxygen species levels. Additionally, ferric hydroxyquinoline incubation did not decrease deferasirox activity in K562 cells suggesting the mechanism of action of the drug is independent from cell iron deprivation by chelation. Finally, incubation with both etoposide and deferasirox induced an increase in K562 apoptotic rate. Conclusions Nuclear factor-κB inhibition by deferasirox is not seen from other chelators and is iron and reactive oxygen species scavenging independent. This could explain the hemoglobin improvement after in vivo treatment, such that our hypothesis needs to be validated in further prospective studies. PMID:20534700

  16. Tenellin acts as an iron chelator to prevent iron-generated reactive oxygen species toxicity in the entomopathogenic fungus Beauveria bassiana.

    Science.gov (United States)

    Jirakkakul, Jiraporn; Cheevadhanarak, Supapon; Punya, Juntira; Chutrakul, Chanikul; Senachak, Jittisak; Buajarern, Taridaporn; Tanticharoen, Morakot; Amnuaykanjanasin, Alongkorn

    2015-01-01

    Iron is an essential element for life. However, the iron overload can be toxic. Here, we investigated the significant increase of tenellin and iron-tenellin complex production in ferricrocin-deficient mutants of Beauveria bassiana. Our chemical analysis indicated that the ferricrocin-deficient mutants T1, T3 and T5 nearly abolished ferricrocin production. In turn, these mutants had significant accumulation of iron-tenellin complex in their mycelia at 247-289 mg g(-1) cell dry weight under iron-replete condition. Both tenellin and iron-tenellin complex were not detected in the wild-type under such condition. Mass analysis of the mutants' crude extracts demonstrated that tenellin formed a 3:1 complex with iron in the absence of ferricrocin. The unexpected link between ferricrocin and tenellin biosynthesis in ferricrocin-deficient mutants could be a survival strategy during iron-mediated oxidative stress.

  17. Iron fertilization with FeEDDHA : the fate and effectiveness of FeEDDHA chelates in soil-plant systems

    NARCIS (Netherlands)

    Schenkeveld, W.D.C.

    2010-01-01

    Iron deficiency chlorosis is a nutritional disorder in plants which reduces crop yields both quantitatively and qualitatively, and causes large economic losses. It occurs world-wide, predominantly in plants grown on calcareous soils, as a result of a limited bioavailability of iron related to the po

  18. [The effect of exogenous antioxidants on the antioxidant status of erythrocytes and hepcidin content in blood of patients with disorders of iron metabolism regulation].

    Science.gov (United States)

    Shcherbinina, S P; Levina, A A; Lisovskaia, I L; Ataullakhanov, F I

    2013-01-01

    In many diseases associated with impairments in iron metabolism, erythrocytes exhibit an increased sensitivity to oxidative stress induced in vitro. In this study, we have examined the antioxidant status of erythrocytes from healthy donors and from 12 patients with disorders of iron homeostasis by measuring the extent of t-BHP-induced hemolysis in vitro. The extent of hemolysis observed with patient erythrocytes was significantly higher than that observed in experiment with normal cells. After therapeutic infusions of the antioxidants mexidol or emoxypin, oxidative hemolysis in patients was restored to normal values and blood hepcidin content increased significantly. A significant correlation was observed between hepcidin concentration after treatment and t-BHP-induced hemolysis before treatment. These data suggest that antioxidants may exert a favorable effect under pathological conditions associated with iron overload disease.

  19. Alkylation of Sulfur Ligand in Cysteinate-Iron Chelates by a 1,2,4,5-Tetraoxane

    Institute of Scientific and Technical Information of China (English)

    刘鹤华; 伍贻康; 沈鑫

    2003-01-01

    Reaction of a 1,2, 4, 5-tetraoxane with cysteinate-iron in the presence of excess methyl cysteinate led to formation of sulfuralkylated methyl cysteinate in 33 % yield, illustrating a possible mechanism for tetraoxanes' antimalarial action.

  20. Effects of iron-glycine chelate on growth, carcass characteristic, liver mineral concentrations and haematological and biochemical blood parameters in broilers.

    Science.gov (United States)

    Kwiecień, M; Samolińska, W; Bujanowicz-Haraś, B

    2015-12-01

    Studies were carried out to determine the effect of additive iron-glycine chelate on the production performance, slaughter yield, mineral deposition in the liver and the metabolic blood panel in broiler chickens. A total of 250 one-day-old Ross 308 chicks were allotted into five groups with five replicates of 10 birds each. Diets were supplemented with the organic form iron (Fe-Gly at the rate of 25%, 50% or 100% of the total requirements of the elements) and inorganic Fe (FeSO4 at the rate of 50% or 100%). In the experiment, iron was added to the premix (containing no Fe) in an amount of 40 or 20 mg per kg of basal diet, in groups I and II, in the form of FeSO4 , and in an amount of 40, 20 or 10 mg per kg of basal diet, in groups III, IV and V, in the form of Fe-Gly. The study covering the period from the first to the 42nd day of breeding revealed that the production performance and slaughter yield were not dependent on the form and amount of added Fe. In the experimental groups with the addition of Fe-Gly of 20 or 10 mg/kg, there were no deaths of chickens during the whole fattening period. As a result, introducing an organic form of iron covering 50% and 25% of the birds' requirement increased the effectiveness of chicken fattening (European Efficiency Index) (p < 0.01). An organic Fe compound (40, 20 or 10 mg/kg) added to mixtures contributed to significant changes in the level of biochemical and haematological indicators in blood. The study demonstrated that an addition of Fe-Gly to mixtures for broilers can be fully effective in terms of production and health performance even if the suggested requirement for this element is 50% or 25% covered.

  1. Current recommendations for chelation for transfusion-dependent thalassemia.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2016-03-01

    Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are closely linked to the adequacy of chelation. Chelation therapy removes accumulated iron and detoxifies iron, which can prevent and reverse much of the iron-mediated organ injury. Currently, three chelators are commercially available--deferoxamine, deferasirox, and deferiprone--and each can be used as monotherapy or in combination. Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation. Other factors, including properties of the individual chelators, ongoing transfusional iron burden, and patient preference, must be considered. Monotherapy generally is utilized if the iron burden is in an acceptable or near-acceptable range and the dose is adjusted accordingly. Combination chelation often is employed for patients with high iron burden, iron-related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose. The combination of deferoxamine and deferiprone is the best studied, but increasing data are available on the safety and efficacy of newer chelator combinations, including deferasirox with deferoxamine and the oral-only combination of deferasirox with deferiprone. The expanding chelation repertoire should enable better control of iron burden and improved outcomes.

  2. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial

    DEFF Research Database (Denmark)

    Lee, Jong Wook; Yoon, Sung-Soo; Shen, Zhi Xiang;

    2010-01-01

    adjustments and ongoing iron intake. Baseline labile plasma iron levels were within normal range despite high serum ferritin levels. The most common drug-related adverse events were nausea (22%) and diarrhea (16%). Serum creatinine increases more than 33% above baseline and the upper limit of normal occurred...... neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www...

  3. Progress of research on the treatment of thalassemia with iron chelators%铁螯合剂在地中海贫血治疗中的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄铭辉; 王云龙; 李永曙

    2012-01-01

    Iron overload is commonly found in patients with some genetic diseases, such as thalassemia. Iron concentration over the normal level will cause severe interference on organs' function. And redox reaction induced by iron would release hydroxyl radical, which causes oxidative injury to several biological macromolecules. So iron chelator therapy should be involved in the treatment of thalassemia. Iron chelators can capture iron ion effectively and improve iron excretion at the same time. So they can decrease the iron level in body and protect the tissues against pathological iron deposition. There are three agents available in clinical now, namely desferrioxam-ine, deferiprone and deferasirox respectively, but each of them has shortages in some aspects. Researchers kept on finding a new kind of iron chelators that would provide better oral bioavailability and minor adverse effects during the last half century. And HBED, DFT, and PIH analogues are expected to be potential clinical iron chelators.%机体铁过载常见于某些遗传性疾病的患者,如地中海贫血.人体铁含量过高可对各脏器功能产生严重影响,并可催化发生氧化还原反应释放羟自由基,破坏多种生物大分子,因此临床对地中海贫血的治疗都需辅以除铁治疗.铁螯合剂可与体内铁离子有效结合并促进铁排泄,降低体内铁含量及其在各器官的病理性沉积.目前临床使用的铁螯合药物有去铁胺、去铁酮和地拉罗司,且均存在局限性.因此,半个世纪以来医药工作者一直致力于寻找口服吸收好、毒副作用小的新药,而HBED,DFT,PIH类化合物有望成为具有临床价值的新铁螯合剂.

  4. Hydrogen peroxide induces a specific DNA base change profile in the presence of the iron chelator 2,2’ dipyridyl in Escherichia coli

    Directory of Open Access Journals (Sweden)

    D.L. Felício

    2009-11-01

    Full Text Available Pretreatment of Escherichia coli cultures with the iron chelator 2,2’-dipyridyl (1 mM protects against the lethal effects of low concentrations of hydrogen peroxide (<15 mM. However, at H2O2 concentrations equal to or greater than 15 mM, dipyridyl pretreatment increases lethality and mutagenesis, which is attributed to the formation of different types of DNA lesions. We show here that pretreatment with dipyridyl (1 mM prior to challenge with high H2O2 concentrations (≥15 mM induced mainly G:C→A:T transitions (more than 100X with 15 mM and more than 250X with 20 mM over the spontaneous mutagenesis rate in E. coli. In contrast, high H2O2 concentrations in the absence of dipyridyl preferentially induced A:T→T:A transversions (more than 1800X and more than 300X over spontaneous mutagenesis for 15 and 20 mM, respectively. We also show that in the fpg nth double mutant, the rpoB gene mutation (RifS-RifR induced by 20 mM H2O2 alone (20X higher was increased in 20 mM H2O2 and dipyridyl-treated cultures (110X higher, suggesting additional and/or different lesions in cells treated with H2O2 under iron deprivation. It is suggested that, upon iron deprivation, cytosine may be the main damaged base and the origin of the pre-mutagenic lesions induced by H2O2.

  5. Accumulation and distribution of iron, cadmium, lead and nickel in cucumber plants grown in hydroponics containing two different chelated iron supplies.

    Science.gov (United States)

    Csog, Árpád; Mihucz, Victor G; Tatár, Eniko; Fodor, Ferenc; Virág, István; Majdik, Cornelia; Záray, Gyula

    2011-07-01

    Cucumber plants grown in hydroponics containing 10 μM Cd(II), Ni(II) and Pb(II), and iron supplied as Fe(III) EDTA or Fe(III) citrate in identical concentrations, were investigated by total-reflection X-ray fluorescence spectrometry with special emphasis on the determination of iron accumulation and distribution within the different plant compartments (root, stem, cotyledon and leaves). The extent of Cd, Ni and Pb accumulation and distribution were also determined. Generally, iron and heavy-metal contaminant accumulation was higher when Fe(III) citrate was used. The accumulation of nickel and lead was higher by about 20% and 100%, respectively, if the iron supply was Fe(III) citrate. The accumulation of Cd was similar. In the case of Fe(III) citrate, the total amounts of Fe taken up were similar in the control and heavy-metal-treated plants (27-31 μmol/plant). Further, the amounts of iron transported from the root towards the shoot of the control, lead- and nickel-contaminated plants were independent of the iron(III) form. Although Fe mobility could be characterized as being low, its distribution within the shoot was not significantly affected by the heavy metals investigated.

  6. Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

    Science.gov (United States)

    Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

    2013-12-01

    The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems.

  7. Antioxidant capacity of parsley cells (Petroselinum crispum L.) in relation to iron-induced ferritin levels and static magnetic field.

    Science.gov (United States)

    Rajabbeigi, Elham; Ghanati, Faezeh; Abdolmaleki, Parviz; Payez, Atefeh

    2013-12-01

    This study was aimed to evaluate antioxidant response of parsley cells to 21 ppm iron and static magnetic field (SMF; 30 mT). The activity of catalase (CAT) and ascorbate peroxidase (APX) and the contents of malonyldialdehyde, iron and ferritin were measured at 6 and 12 h after treatments. Exposure to SMF increased the activity of CAT in treated cells, while combination of iron and SMF treatments as well as iron supply alone decreased CAT activity, compared to that of control cells. Combination of SMF with iron treatment reduced iron content of the cells and ameliorated mal effect of iron on CAT activity. All treatments reduced APX activity; however, the content of total ascorbate increased in response to iron and SMF+iron. The results showed that among the components of antioxidant system of parsley cells, enhanced activity of CAT in SMF-treated cells and increase of ascorbate in SMF+Fe-treated ones were responsible for the maintenance of membranes integrity. Ferritin contents of SMF- and SMF+Fe-treated cells also decreased significantly 12 h after treatments, compared to those of the control cells. These results cast doubt on the proposed functions of ferritin as a putative reactive oxygen species detoxifying molecule.

  8. 不同铁螯合剂治疗输血依赖性铁过载的对比研究%A comparative study of different iron chela-tion therapy transfusion dependent iron over-load

    Institute of Scientific and Technical Information of China (English)

    李仙松; 杜娟; 李伟平

    2014-01-01

    目的:对比不同铁螯合剂对贫血患者长期输血治疗后铁过载的驱铁作用及安全性。方法:将24例反复输血的患者在血清铁蛋白(SF)水平相同条件下随机均分为三组,采用不同铁螯合剂去铁治疗,分别检测其在治疗后1个月、2个月、3个月的铁蛋白(SF)水平,并观察其治疗相关不良反应。结果:地拉罗司组在治疗后SF下降最明显,且不良反应最少。结论:地拉罗司治疗输血依赖性铁过载的效果最好,安全性较高,不良反应最少。%AIM:To compare the effects and safety of iron over-load of patients with anemia who received different iron chelators treatment after long-term transfusion.METHODS:Dividing the 24 patients who transfused blood repeatedly into three groups un-der the same condition of serum ferritin (SF)level for iron remov-al treatment with different iron chelators.Then we detected the se-rum ferritin (SF)level after treatment of 1 month,2 months and 3 months respectively,and observed the adverse reactions relative-ly.RESULTS:The group with Deferasirox that the SF level de-creased at most and had minimal adverse reactions after treat-ment.CONCLUSION:The best therapeutic efficacy for iron o-verload of transfusion dependency is Deferasirox which has high safety and minimal adverse reactions.

  9. Iron Deficiency-induced Increase of Root Branching Contributes to the Enhanced Root Ferric Chelate Reductase Activity

    Institute of Scientific and Technical Information of China (English)

    Chong-Wei Jin; Wei-Wei Chen; Zhi-Bin Meng; Shao-Jian Zheng

    2008-01-01

    In various plant species, Fe deficiency increases lateral root branching. However, whether this morphological alteration contributes to the Fe deficiency-induced physiological responses still remains to be demonstrated. In the present research, we demonstrated that the lateral root development of red clover (Trifolium pretense L.) was significantly enhanced by Fe deficient treatment, and the total lateral root number correlated well with the Fe deficiency-induced ferric chelate reductase (FCR) activity. By analyzing the results from Dasgan et al. (2002), we also found that although the two tomato genotypes line227/1 (P1) and Roza (P2) and their reciprocal F1 hybrid lines ("P1 × P2" and "P2 × P1 ") were cultured under two different lower Fe conditions (10-6 and 10-7 M FeEDDHA), their FCR activities are significantly correlated with the lateral root number. More interestingly, the -Fe chlorosis tolerant ability of these four tomato lines displays similar trends with the lateral root density. Taking these results together, it was proposed that the Fe deficiency-induced increases of the lateral root should play an important role in resistance to Fe deficiency, which may act as harnesses of a useful trait for the selection and breeding of more Fe-efficiant crops among the genotypes that have evolved a Fe deficiency-induced Fe uptake system.

  10. Overview of chelation recommendations for thalassaemia and sickle cell disease

    Directory of Open Access Journals (Sweden)

    Banu Kaya

    2014-12-01

    Full Text Available The long term consequences of iron toxicity are mostly reversible with effective iron chelation therapy. Recommendations for use of chelation therapy in transfusion dependent thalassaemia (TDT, sickle cell disease (SCD and non transfusion dependent thalassaemia (NTDT continue to evolve as our knowledge and clinical experience increases. Improved chelation options including drug combinations and a better understanding of condition specific factors may help to improve efficiency of chelation regimens and meet the needs of patients more effectively.

  11. Application prospect of iron chelator in the prevention and therapy of osteoporosis%铁螯合剂在骨质疏松防治中的应用前景

    Institute of Scientific and Technical Information of China (English)

    赵国阳; 徐又佳

    2015-01-01

    Iron overload may lead to the occurrence and development of osteoporosis, and drug of decreasing i-ron overload may also have clinical potential for osteoporosis patients with iron overload.Currently, the commonly used drugs of decreasing iron are various kinds of iron chelators, which mainly include deferoxamine, deferiprone, and defera-sirox.Here is to summarize the characteristics of three iron chelators, combine with their effects on bone metabolism, and explore their clinical prospect as osteoporosis treatment.%铁过载可导致骨质疏松,降低铁过载的药物有望用于防治伴有铁过载的骨质疏松症。目前临床使用的降低铁过载药物是各种铁鳌合剂,包括去铁胺、去铁酮和地拉罗司。本文总结这3种铁螯合剂临床使用特点,结合其对骨代谢影响实验研究结果,探讨铁鳌合剂作为抗骨质疏松用药的前景。

  12. Phenolipids as antioxidants in emulsified systems

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit Moltke; Bayrasy, Christelle; Laguerre, Mickäel

    to an increase of the antioxidative effect. When the phenolic compound reaches a certain point of lipophilicity its antioxidative effect decreases. Thus, the polar paradox hypothesis is not valid when the alkyl chain length is above a certain length. Futhermore, the length of the alkyl chain for optimal...... antioxidant effect has been shown to be influenced by the specific phenolic compound and the type of emulsion. The overall aim for our work was to evaluate phenolipids with different lipophilicity as antioxidants in emulsified food. In the study presented here caffeic, ferulic and coumaric acid were selected...... along with their corresponding alkyl esters (C4-C20). The methods used to evaluate the antioxidative effect of the different phenolipids were the CAT assay (o/w emulsion), antioxidant assays (DPPH, Iron chelating and reducing power) and partitioning studies. Moreover, the results from the CAT assay...

  13. [Anomalies of the masticatory apparatus in beta-thalassemia. The present status after transfusion and iron-chelating therapy].

    Science.gov (United States)

    Scutellari, P N; Orzincolo, C; Andraghetti, D; Gamberini, M R

    1994-04-01

    Fifty-four homozygous beta-thalassemic patients (26 men and 28 women) aged 7 to 24 years, who had been treated with high transfusion regimen (Hb levels = 9-10 g/dl) and chelation therapy (desferrioxamine, 35-50 mg/kg), underwent clinical and radiographic investigations. This study was aimed at assessing the clinical and radiographic changes in the stomatognathic system (teeth, mandible and maxilla, occlusion relationship and dental bases). All patients underwent orthopantomography and teleradiography of the skull, in the lateral view. Twenty thalassemic patients (13 men and 7 women) of the same age but treated with low transfusion regimes (Hb levels = 5-6 g/dl) were examined as a control group. Our results indicate that: 1) in the control group, osteopenia is the specific lesion of anemia, in both the alveolar process and the mandible, following marrow expansion. Consequently, diastema of incisors and several types of malocclusion follow--i.e., overjet, anterior open-bite and crossbite, nearly all of them associated with II dental and skeletal patterns of Angle's classification. 2) In adequately transfused patients, no lesions are observed in 55% of cases, in both the teeth and the facial skeleton. This means that current treatment methods can prevent bone abnormalities, especially if transfusions begin at birth. Nevertheless, osteopenia of the mandible (31.4%) and dental and/or skeletal malocclusions (40.7%) remain in many cases, because of persistent marrow expansion, which usually follows incorrect treatment. 3) General dental diseases--e.g., caries, paradentosis, gingivitis, etc.--affect both populations with the same incidence.

  14. Quercetin-Iron Complex: Synthesis, Characterization, Antioxidant, DNA Binding, DNA Cleavage, and Antibacterial Activity Studies.

    Science.gov (United States)

    Raza, Aun; Xu, Xiuquan; Xia, Li; Xia, Changkun; Tang, Jian; Ouyang, Zhen

    2016-11-01

    Quercetin-iron (II) complex was synthesized and characterized by elemental analysis, ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, mass spectrometry, proton nuclear magnetic resonance spectroscopy, thermogravimetry and differential scanning calorimetry, scanning electron micrography and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal:ligand) of the complex. Antioxidant study of the quercetin and its metal complex against 2, 2-di-phenyl-1-picryl hydrazyl radical showed that the complex has much more radical scavenging activity than free quercetin. The interaction of quercetin-iron (II) complex with DNA was determined using ultraviolet visible spectra, fluorescence spectra and agarose gel electrophoresis. The results showed that quercetin-iron (II) complex can intercalate moderately with DNA, quench a strong intercalator ethidium bromide and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form to nicked circular form and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was an oxidative cleavage pathway. These results revealed the potential nuclease activity of complex to cleave DNA. In addition, antibacterial activity of complex on E.coli and S. aureus was also investigated. The results showed that complex has higher antibacterial activity than ligand.

  15. Effect of some naturally occurring iron ion chelators on the formation of radicals in the reaction mixtures of rat liver microsomes with ADP, Fe3+ and NADPH

    Science.gov (United States)

    Minakata, Katsuyuki; Fukushima, Kazuaki; Nakamura, Masayuki; Iwahashi, Hideo

    2011-01-01

    In order to clarify the mechanism by polyphenols of protective effects against oxidative damage or by quinolinic acid of its neurotoxic and inflammatory actions, effects of polyphenols or quinolinic acid on the radical formation were examined. The ESR measurements showed that some polyphenols such as caffeic acid, catechol, gallic acid, D-(+)-catechin, L-dopa, chlorogenic acid and L-noradrenaline inhibited the formation of radicals in the reaction mixture of rat liver microsomes with ADP, Fe3+ and NADPH. The ESR measurements showed that α-picolinic acid, 2,6-pyridinedicarboxylic acid and quinolinic acid (2,3-pyridinedicarboxylic acid) enhanced the formation of radicals in the reaction mixture of rat liver microsomes with Fe3+ and NADPH. Caffeic acid and α-picolinic acid had no effects on the formation of radicals in the presence of EDTA, suggesting that the chelation of iron ion seems to be related to the inhibitory and enhanced effects. The polyphenols may exert protective effects against oxidative damage of erythrocyte membrane, ethanol-induced fatty livers, cardiovascular diseases, inflammatory and cancer through the mechanism. On the other hand, quinolinic acid may exert its neurotoxic and inflammatory effects because of the enhanced effect on the radical formation. PMID:22128221

  16. Effect of some naturally occurring iron ion chelators on the formation of radicals in the reaction mixtures of rat liver microsomes with ADP, Fe and NADPH.

    Science.gov (United States)

    Minakata, Katsuyuki; Fukushima, Kazuaki; Nakamura, Masayuki; Iwahashi, Hideo

    2011-11-01

    In order to clarify the mechanism by polyphenols of protective effects against oxidative damage or by quinolinic acid of its neurotoxic and inflammatory actions, effects of polyphenols or quinolinic acid on the radical formation were examined. The ESR measurements showed that some polyphenols such as caffeic acid, catechol, gallic acid, D-(+)-catechin, L-dopa, chlorogenic acid and L-noradrenaline inhibited the formation of radicals in the reaction mixture of rat liver microsomes with ADP, Fe(3+) and NADPH. The ESR measurements showed that α-picolinic acid, 2,6-pyridinedicarboxylic acid and quinolinic acid (2,3-pyridinedicarboxylic acid) enhanced the formation of radicals in the reaction mixture of rat liver microsomes with Fe(3+) and NADPH. Caffeic acid and α-picolinic acid had no effects on the formation of radicals in the presence of EDTA, suggesting that the chelation of iron ion seems to be related to the inhibitory and enhanced effects. The polyphenols may exert protective effects against oxidative damage of erythrocyte membrane, ethanol-induced fatty livers, cardiovascular diseases, inflammatory and cancer through the mechanism. On the other hand, quinolinic acid may exert its neurotoxic and inflammatory effects because of the enhanced effect on the radical formation.

  17. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers.

    Science.gov (United States)

    Skerjanec, Andrej; Wang, Jixian; Maren, Kelly; Rojkjaer, Lisa

    2010-02-01

    Deferasirox, a newly developed iron chelator, was coadministered orally with either a known inducer of drug metabolism or with cosubstrates for cytochrome P450 (CYP) to characterize the potential for drug-drug interactions. In the induction assessment, single-dose deferasirox pharmacokinetics were obtained in the presence and absence of a repeated-dose regimen of rifampin. In the CYP3A interaction evaluation, midazolam and its active hydroxylated metabolite were assessed after single doses of midazolam in the presence and absence of steady-state concentrations of deferasirox. To test for interaction at the level of CPY2C8, single-dose repaglinide pharmacokinetics/pharmacodynamics were determined with and without repeated-dose administration of deferasirox. After rifampin, a significant reduction (44%) in plasma exposure (AUC) to deferasirox was observed. Upon coadministration of midazolam, there was a modest reduction of up to 22% in midazolam exposure (AUC, C(max)), suggesting a modest induction of CYP3A4/5 by deferasirox. Def erasirox caused increases in repaglinide plasma C(max) and AUC of 1.5-fold to over 2-fold, respectively, with little change in blood glucose measures. Specific patient prescribing recommendations were established when coadministering deferasirox with midazolam, repaglinide, and rifampin. These recommendations may also apply to other substrates of CYP3A4/5 and CYP2C8 or potent inducers of glucuronidation.

  18. Tratamento da anemia ferropriva com ferro quelato glicinato e crescimento de crianças na primeira infância Treatment of iron deficiency anemia with iron bis-glycinate chelate and growth of young children

    Directory of Open Access Journals (Sweden)

    Luciana Cisoto Ribeiro

    2008-10-01

    Full Text Available OBJETIVO: Avaliar a resposta à suplementação diária com ferro quelato glicinato e seu impacto sobre o crescimento linear. MÉTODOS: Realizou-se um estudo prospectivo com 790 crianças, de 6 a 36 meses, que freqüentavam creches municipais de São Paulo no período de 1999 a 2003. Ao início e ao final do estudo a hemoglobina, o peso corporal e a estatura/comprimento foram coletados. Utilizou-se suplemento contendo ferro quelato glicinato em gotas na dose de 5mg Fe elementar/kg peso/dia, administrado na própria instituição pelo profissional de saúde da creche, por um período de 12 semanas. RESULTADOS: A suplementação resultou em um significante e positivo efeito sobre os níveis de hemoglobina. A resposta ao tratamento foi positiva em 85,3% das crianças, com um aumento médio de 1,6g/dL nos valores de hemoglobina (pOBJECTIVE: The objective of this study was to evaluate response to daily supplementation with iron bis-glycinate chelate and its impact on linear growth. METHODS: A prospective study was done with 790 children aging from 6 to 36 months who attended daycare in São Paulo from 1999 to 2003. Hemoglobin levels, body weight and height/length were determined at the beginning and end of the study. Liquid iron bis-glycinate chelate was administered in a dosage of 5mg of elemental iron/kg of body weight/day given by the health provider of the daycare facility for a period of 12 weeks. RESULTS: Supplementation resulted in a significant, positive effect on the hemoglobin levels of 85.3% of the children with a mean increase of 1.6g/dL (p<0.001. In children aging from 25 to 36 months and in those with lower hemoglobin levels at the beginning of supplementation, there was a significantly higher increase. No gastrointestinal problem or intolerance to the supplement was observed during the intervention period. Supplementation also had an impact on growth and on the height-for-age indicator (z-score in children older than 12 months but

  19. Preparation and antioxidant activity evaluation of cod skin peptides chelated calcium%鳕鱼皮复合肽螯合钙的制备及抗氧化活性研究

    Institute of Scientific and Technical Information of China (English)

    黄薇; 邓尚贵; 唐艳; 李淑芳; 孔巧香

    2012-01-01

    This paper focused on the preparation of cod skin protein chelating Ca^2+ by compound enzymolysis method, and studied the antioxidation function of the chelate. The results showed that the optimal chelation reaction between hydrolysates and CaCl2 conducted for 20 min at 25 ℃ and pH 7.0 with a calcium/peptide mass ratio of 0.3/3, yielded 58.85% of Ca^2+ chelating rate. The chelated products exhibited inhibitory effects on hydroxyl radical and super oxide anion radical.%利用木瓜蛋白酶与风味酶组合成的复合酶对鳕鱼皮蛋白进行酶解,制得酶解液,以氯化钙为钙源,与多肽酶解液反应制备多肽螯合钙,并对其抗氧化性进行了研究。结果表明,制备多肽螯合钙的最佳条件是:氯化钙与多肽的质量比为0.3:3,pH值为7.0,反应温度为25℃,反应时间为20min,在此条件下钙离子的螯合率为58.85%,产物对羟自由基(·OH)和超氧阴离子自由基(O2^-·)均有较强的清除作用。

  20. Effects of iron on growth, antioxidant enzyme activity, bound extracellular polymeric substances and microcystin production of Microcystis aeruginosa FACHB-905.

    Science.gov (United States)

    Wang, Chao; Wang, Xun; Wang, Peifang; Chen, Bin; Hou, Jun; Qian, Jin; Yang, Yangyang

    2016-10-01

    Toxic cyanobacterial blooms have occurred in various water bodies during recent decades and made serious health hazards to plants, animals and humans. Iron is an important micronutrient for algal growth and recently, the concentration of which has increased remarkably in freshwaters. In this paper, the cyanobacterium Microcystis aeruginosa FACHB-905 was cultivated under non-iron (0μM), iron-limited (10μM) and iron-replete (100μM) conditions to investigate the effects of iron on growth, antioxidant enzyme activity, EPS and microcystin production. The results showed that algal cell density and chlorophyll-a content were maximal at the highest iron concentration. Antioxidant enzymes activity increased notably under all three conditions in the early stage of experiment, of which the SOD activity recovered soon from oxidative stress in 10μM group. The productions of some protein-like substances and humic acid-like substances of bound EPS were inhibited in iron-containing groups in the early stage of experiment while promoted after the adaptation period of Microcystis aeruginosa. Iron addition is a factor affecting the formation of cyanobacterial blooms through its impact on the content of LB-EPS and the composition of TB-EPS. The intracellular MC-LR concentration and the productivity potential of MC-LR were the lowest in 0μM group and highest in 10μM group. No obvious extracellular release of MC-LR was observed during the cultivation time. Therefore, iron addition can promote the physiological activities of M. aeruginosa, but a greater harm could be brought into environment under iron-limited (10μM) condition than under iron-replete (100μM) condition.

  1. Role of chelates in treatment of cancer

    Directory of Open Access Journals (Sweden)

    Tripathi Laxmi

    2007-01-01

    Full Text Available Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc, organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.

  2. Combination Iron Chelation Therapy with Deferiprone and Deferasirox in Iron-Overloaded Patients with Transfusion-Dependent β-Thalassemia Major

    Science.gov (United States)

    Karami, Hossein; Kosaryan, Mehrnoush; Amree, Arash Hadian; Darvishi-Khezri, Hadi; Mousavi, Masoomeh

    2017-01-01

    There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms) before and after treatment, respectively (p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in β-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading. PMID:28243431

  3. Models of the iron-only hydrogenase: a comparison of chelate and bridge isomers of Fe2(CO)4{Ph2PN(R)PPh2}(μ-pdt) as proton-reduction catalysts.

    Science.gov (United States)

    Ghosh, Shishir; Hogarth, Graeme; Hollingsworth, Nathan; Holt, Katherine B; Richards, Idris; Richmond, Michael G; Sanchez, Ben E; Unwin, David

    2013-05-21

    Reactions of Fe2(CO)6(μ-pdt) (pdt = SCH2CH2CH2S) with aminodiphosphines Ph2PN(R)PPh2 (R = allyl, (i)Pr, (i)Bu, p-tolyl, H) have been carried out under different conditions. At room temperature in MeCN with added Me3NO·2H2O, dibasal chelate complexes Fe2(CO)4{κ(2)-Ph2PN(R)PPh2}(μ-pdt) are formed, while in refluxing toluene bridge isomers Fe2(CO)4{μ-Ph2PN(R)PPh2}(μ-pdt) are the major products. Separate studies have shown that chelate complexes convert to the bridge isomers at higher temperatures. Two pairs of bridge and chelate isomers (R = allyl, (i)Pr) have been crystallographically characterised together with Fe2(CO)4{μ-Ph2PN(H)PPh2}(μ-pdt). Chelate complexes adopt the dibasal diphosphine arrangement in the solid state and exhibit very small P-Fe-P bite-angles, while the bridge complexes adopt the expected cisoid dibasal geometry. Density functional calculations have been carried out on the chelate and bridge isomers of the model compound Fe2(CO)4{Ph2PN(Me)PPh2}(μ-pdt) and reveal that the bridge isomer is thermodynamically favourable relative to the chelate isomers that are isoenergetic. The HOMO in each of the three isomers exhibits significant metal-metal bonding character, supporting a site-specific protonation of the iron-iron bond upon treatment with acid. Addition of HBF4·Et2O to the Fe2(CO)4{κ(2)-Ph2PN(allyl)PPh2}(μ-pdt) results in the clean formation of the corresponding dibasal hydride complex [Fe2(CO)4{κ(2)-Ph2PN(allyl)PPh2}(μ-H)(μ-pdt)][BF4], with spectroscopic measurements revealing the intermediate formation of a basal-apical isomer. A crystallographic study reveals that there are only very small metric changes upon protonation. In contrast, the bridge isomers react more slowly to form unstable species that cannot be isolated. Electrochemical and electrocatalysis studies have been carried out on the isomers of Fe2(CO)4{Ph2PN(allyl)PPh2}(μ-pdt). Electron accession is predicted to occur at an orbital that is anti-bonding with respect to

  4. Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange

    Science.gov (United States)

    Gattermann, Norbert; Jarisch, Andrea; Schlag, Rudolf; Blumenstengel, Klaus; Goebeler, Mariele; Groschek, Matthias; Losem, Christoph; Procaccianti, Maria; Junkes, Alexia; Leismann, Oliver; Germing, Ulrich

    2012-01-01

    EXtend and eXjange were prospective, 1-yr, non-interventional, observational, multicentre studies that investigated deferasirox, a once-daily oral iron chelator, in iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes (MDS), respectively, treated in the daily-routine setting of office-based physicians. No inclusion or exclusion criteria or additional monitoring procedures were applied. Deferasirox was administered as recommended in the European Summary of Product Characteristics. Haematological parameters and adverse events (AEs) were collected at two-monthly intervals. Data from 123 chelation-naïve patients with MDS (mean age 70.4 yrs) with median baseline serum ferritin level of 2679 (range 184–16 500) ng/mL, and 44 prechelated patients with MDS (mean age 69.6 yrs) with median baseline serum ferritin level of 2442 (range 521–8565) ng/mL, were assessed. The mean prescribed daily dose of deferasirox at the first visit was 15.7 and 18.7 mg/kg/d, respectively. Treatment with deferasirox produced a significant reduction in median serum ferritin levels in chelation-naïve patients with MDS from 2679 to 2000 ng/mL (P = 0.0002) and a pronounced decrease in prechelated patients with MDS from 2442 to 2077 ng/mL (P = 0.06). The most common drug-related AEs were gastrointestinal, increased serum creatinine levels and rash. These studies demonstrate that deferasirox used in physicians’ medical practices is effective in managing iron burden in transfusion-dependent patients with MDS. PMID:22023452

  5. Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange.

    Science.gov (United States)

    Gattermann, Norbert; Jarisch, Andrea; Schlag, Rudolf; Blumenstengel, Klaus; Goebeler, Mariele; Groschek, Matthias; Losem, Christoph; Procaccianti, Maria; Junkes, Alexia; Leismann, Oliver; Germing, Ulrich

    2012-03-01

    EXtend and eXjange were prospective, 1-yr, non-interventional, observational, multicentre studies that investigated deferasirox, a once-daily oral iron chelator, in iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes (MDS), respectively, treated in the daily-routine setting of office-based physicians. No inclusion or exclusion criteria or additional monitoring procedures were applied. Deferasirox was administered as recommended in the European Summary of Product Characteristics. Haematological parameters and adverse events (AEs) were collected at two-monthly intervals. Data from 123 chelation-naïve patients with MDS (mean age 70.4 yrs) with median baseline serum ferritin level of 2679 (range 184-16,500) ng/mL, and 44 prechelated patients with MDS (mean age 69.6 yrs) with median baseline serum ferritin level of 2442 (range 521-8565) ng/mL, were assessed. The mean prescribed daily dose of deferasirox at the first visit was 15.7 and 18.7 mg/kg/d, respectively. Treatment with deferasirox produced a significant reduction in median serum ferritin levels in chelation-naïve patients with MDS from 2679 to 2000 ng/mL (P = 0.0002) and a pronounced decrease in prechelated patients with MDS from 2442 to 2077 ng/mL (P = 0.06). The most common drug-related AEs were gastrointestinal, increased serum creatinine levels and rash. These studies demonstrate that deferasirox used in physicians' medical practices is effective in managing iron burden in transfusion-dependent patients with MDS.

  6. In vitro Antioxidant Activities of Sodium Zinc and
Sodium Iron Chlorophyllins from Pine Needles

    Science.gov (United States)

    Zhan, Ruzhen; Wu, Jian

    2014-01-01

    Summary Chlorophyll was extracted from pine needles, and then sodium zinc chlorophyllin (SZC) and sodium iron chlorophyllin (SIC) were synthesised by saponification, purification and substitution reaction, using sodium copper chlorophyllin (SCC) as a control. Their crystalline structures were verified by atomic absorbance spectroscopy, UV-VIS spectroscopy and HPLC. Moreover, their antioxidant activities were evaluated and compared with that of ascorbic acid through four biochemical assays: DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of β-carotene bleaching and O2– scavenging activity. SZC had better antioxidant properties at a lower dosage than SIC and SCC in all assays. In the β-carotene bleaching assay, EC50 of SZC, SIC and SCC was 0.04, 0.38 and 0.90 mg/mL, respectively, much lower than that of ascorbic acid (4.0 mg/mL). SZC showed a better result (pchlorophyllins had lower activities than ascorbic acid. These results demonstrated the potential bioactivities of chlorophyll derivatives and supported their possible role in human health protection and disease prevention. PMID:27904324

  7. Overview of current chelation practices

    Directory of Open Access Journals (Sweden)

    Y. Aydinok

    2011-12-01

    Full Text Available Deferoxamine (DFO is reference standard therapy for transfusional iron overload since the 1980s. Although it is a highly effective iron chelator, the compliance problem to subcutaneous administration of DFO remains as the major problem. The oral chelator Deferiprone (DFP has no marketing licence in North America, however, it has been licensed in India since 1994 and the European Union (EU granted marketing approval for DFP in 1999, specifically for patients with thalassemia major when DFO is inadequate, intolerable or unacceptable. There are still limited data available on the use of DFP in children between 6 and 10 years of age, and no data on DFP use in children under 6 years of age. Subsequently the oral chelator Deferasirox (DFX was approved by FDA and EMA for the treatment of patients with transfusional iron overload -older than 2 years of age- as first line therapy, in 2005 and 2006 respectively. The primary objective of iron chelation is to maintain body iron at safe levels at all times but once iron is accumulated, the objective of iron chelation is to reduce tissue iron to safe levels which is a slow process. The chelation regimen, dose and frequency of administration, of the chelator(s are mainly determined based on body iron burden, presence of myocardial iron and the transfusional iron loading rate. A proper monitoring of chelation is of importance for measuring the response rate to a particular regimen and providing dose adjustments to enhance chelation efficacy and to avoid toxicity. Efficacy of a chelation regimen may exhibit individual variability resulting from factors such as absorbtion and metabolism of the chelator. Tolerability and compliance are also individual variables effecting the response to chelation. Understanding of advantages and limitations of chelators, accurately determining chelation needs of patients with iron overload and designing individualized chelation regimens with less toxicity but optimum efficacy

  8. Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions.

    Science.gov (United States)

    Mozdzan, Monika; Szemraj, Janusz; Rysz, Jacek; Nowak, Dariusz

    2005-05-01

    Carnosine has antioxidant properties and is efficient in the treatment of chemically-induced inflammatory lesions in animals. However, some studies question its biological significance as antioxidant and show lack of protection and even pro-oxidant effect of carnosine in systems containing nickel and iron ions. The ability of carnosine to: (1) reduce Fe(3+) into Fe(2+) ions; (2) protect deoxyribose from oxidation by Fe(2+)-, Fe(3+)-, and Cu(2+)-H(2)O(2)-EDTA systems; (3) protect DNA from damage caused by Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems; (4) inhibit HClO- and H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence was tested in vitro. At concentration 10 mM carnosine reduced 16.6+/-0.5 nmoles of Fe(3+) into Fe(2+) ions during 20 min. incubation and added to plasma significantly increased its ferric reducing ability. Inhibition of deoxyribose oxidation by 10 mM carnosine reached 56+/-5, 40+/-11 and 30+/-11% for systems containing Fe(2+), Fe(3+) and Cu(2+) ions, respectively. The damage to DNA was decreased by 84+/-9 and 61+/-14% when Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems were applied. Combination of 10 mM histidine with alanine or histidine alone (but not alanine) enhanced 1.3 and 2.3 times (Peffect on DNA. Carnosine at 10 and 20 mM decreased by more than 90% light emission from both chemiluminescent systems. It is concluded that carnosine has significant antioxidant activity especially in the presence of transition metal ions. However, hydrolysis of carnosine with subsequent histidine release may be responsible for some pro-oxidant effects.

  9. Antioxidants

    Science.gov (United States)

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  10. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.

    Directory of Open Access Journals (Sweden)

    Leonardo Victor Barbosa Pereira

    Full Text Available The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC. Male Wistar rats were submitted to 5/6 nephrectomy (Nx to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine was administrated (1.5 mM/KgBW, intravenously 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7; 2--Nx+NAC (n = 6; 3--Nx+Gd (n = 7; 4--Nx+NAC+Gd (4.8 g/L in drinking water, initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6. This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW, proteinuria (mg/24 hs, serum iron (µg/dL; serum ferritin (ng/mL; transferrin saturation (%, TIBC (µg/dL and TBARS (nmles/ml. Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

  11. Enhanced antioxidation and electromagnetic properties of Co-coated flaky carbonyl iron particles prepared by electroless plating

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yingying, E-mail: zyzlchappy1989@163.com [State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi’an, Shaanxi 710072 (China); Zhou, Wancheng [State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi’an, Shaanxi 710072 (China); Li, Rong [State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi’an, Shaanxi 710072 (China); No. 603 Faculty, Xi’an Institute of High Technology, Xi’an 710025 (China); Mu, Yang; Qing, Yuchang [State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi’an, Shaanxi 710072 (China)

    2015-07-15

    Highlights: • Co-coated carbonyl iron particles were prepared by electroless plating method. • The obvious weight gain of carbonyl iron was deferred to 400 °C after Co-coated. • The permeability of the Co-coated particle composite kept almost invariable. • Co-coated carbonyl iron composite reserves a better absorption after heat treatment. - Abstract: Co was successfully coated on the surface of flaky carbonyl iron particles using an electroless plating method. The morphologies, composition, as well as magnetic, antioxidation and electromagnetic properties of the samples were characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), vibrating sample magnetometer (VSM), thermogravimetric (TG) and microwave network analyzer. TG curve shows that the obvious weight gain of carbonyl iron was deferred from 300 to 400 °C after Co-coated. In contrast to raw carbonyl iron, the Co-coated carbonyl iron shows better stability on electromagnetic properties after 300 °C heat treatment for 10 h, demonstrating that the Co coating can act as the protection of carbonyl iron.

  12. A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements.

    Science.gov (United States)

    Bay, A; Dogan, M; Bulan, K; Kaba, S; Demir, N; Öner, A F

    2013-09-01

    Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month. There are a few studies on serum trace element levels of patients with pica. The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA). The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet. The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls. The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group. Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group. Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group. Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress. These effects should be kept in mind while managing patients with pica.

  13. Affinity purification of copper-chelating peptides from sunflower protein hydrolysates.

    Science.gov (United States)

    Megías, Cristina; Pedroche, Justo; Yust, Maria M; Girón-Calle, Julio; Alaiz, Manuel; Millan, Francisco; Vioque, Javier

    2007-08-08

    Copper-chelating peptides were purified from sunflower protein hydrolysates by affinity chromatography using immobilized copper. A variety of protein hydrolysates were obtained by incubation with the proteases Alcalase and Flavourzyme for different periods of time. Chelating activity was indirectly determined by measuring the inhibitory effect of hydrolysates on the oxidation of beta-carotene by copper. Copper-binding peptides purified from the two hydrolysates that inhibited oxidation by copper the most contained 25.4 and 42.0% histidine and inhibited beta-carotene oxidation 8 and 3 times more than the original hydrolysates, which had 2.4 and 2.6% histidine, respectively. Thus, histidine content is not the only factor involved in antioxidant activity, and probably other factors such as peptide size and amino acid sequence are also important. This work shows that affinity chromatography can be used for the purification of copper-chelating peptides and probably other metals of nutritional interest such as calcium, iron, and zinc. In addition to their antioxidant potential, chelating peptides are of nutritional interest because they increase bioavailability of minerals.

  14. Iron chelation therapy of transfusion-dependent β-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic?

    Science.gov (United States)

    Diamantidis, Michael D; Neokleous, Nikolaos; Agapidou, Aleka; Vetsiou, Evaggelia; Manafas, Achilles; Fotiou, Paraskevi; Vlachaki, Efthymia

    2016-05-01

    The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with β-Thalassemia Μajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk.

  15. Beliefs about chelation among thalassemia patients

    Directory of Open Access Journals (Sweden)

    Trachtenberg Felicia L

    2012-12-01

    Full Text Available Abstract Background Understanding patients’ views about medication is crucial to maximize adherence. Thalassemia is a congenital blood disorder requiring chronic blood transfusions and daily iron chelation therapy. Methods The Beliefs in Medicine Questionnaire (BMQ was used to assess beliefs in chelation in thalassemia patients from North America and London in the Thalassemia Longitudinal Cohort (TLC of the Thalassemia Clinical Research Network (TCRN. Chelation adherence was based on patient report of doses administered out of those prescribed in the last four weeks. Results Of 371 patients (ages 5-58y, mean 24y, 93% were transfused and 92% receiving chelation (26% deferoxamine (DFO; a slow subcutaneous infusion via portable pump, 63% oral, 11% combination. Patients expressed high “necessity” for transfusion (96%, DFO chelation (92% and oral chelation (89%, with lower “concern” about treatment (48%, 39%, 19% respectively. Concern about oral chelation was significantly lower than that of DFO (p Conclusions Despite their requirement for multimodal therapy, thalassemia patients have positive views about medicine, more so than in other disease populations. Patients may benefit from education about the tolerability of chelation and strategies to effectively cope with side effects, both of which might be beneficial in lowering body iron burden. Clinicaltrials.gov identifier NCT00661804

  16. Effects of methionine chelate- or yeast proteinate-based supplement of copper, iron, manganese and zinc on broiler growth performance, their distribution in the tibia and excretion into the environment.

    Science.gov (United States)

    Singh, Abhay Kumar; Ghosh, Tapan Kumar; Haldar, Sudipto

    2015-04-01

    A straight-run flock of 1-day-old Cobb 400 chicks (n = 432) was distributed into four treatment groups (9 replicate pens in each group, 12 birds in a pen) for a 38-day feeding trial evaluating the effects of a methionine chelate (Met-TM)- or a yeast proteinate (Yeast-TM)-based supplement of copper (Cu), iron (Fe), manganese (Mn) and zinc (Zn) on growth performance, bone criteria and some metabolic indices in commercial broiler chickens. The diets were either not supplemented with any trace elements at all (negative control, NC) or supplemented with an inorganic (sulphate) trace element premix (inorganic TM (ITM), 1 g/kg feed), the Met-TM (1 g/kg feed) and the Yeast-TM (0.5 g/kg feed). Body weight, feed conversion ratio and dressed meat yield at 38 days were better in the Yeast-TM-supplemented group as compared with the NC, ITM and Met-TM groups (p chelates or yeast proteinate forms of Cu, Fe, Mn and Zn improved body weight and feed conversion ratio (FCR) and markedly reduced excretion of the said trace elements. The study revealed that it may be possible to improve broiler performance and reduce excretion of critical trace elements into the environment by complete replacement of inorganic trace minerals from their dietary regime and replacing the same with methionine chelate or yeast proteinate forms.

  17. Lipid peroxidation, antioxidant enzymes and glutathione levels in human erythrocytes exposed to colloidal iron hydroxide in vitro

    Directory of Open Access Journals (Sweden)

    Ferreira A.L.A.

    1999-01-01

    Full Text Available The free form of the iron ion is one of the strongest oxidizing agents in the cellular environment. The effect of iron at different concentrations (0, 1, 5, 10, 50, and 100 µM Fe3+ on the normal human red blood cell (RBC antioxidant system was evaluated in vitro by measuring total (GSH and oxidized (GSSG glutathione levels, and superoxide dismutase (SOD, catalase, glutathione peroxidase (GSH-Px and reductase (GSH-Rd activities. Membrane lipid peroxidation was assessed by measuring thiobarbituric acid reactive substance (TBARS. The RBC were incubated with colloidal iron hydroxide and phosphate-buffered saline, pH 7.45, at 37oC, for 60 min. For each assay, the results for the control group were: a GSH = 3.52 ± 0.27 µM/g Hb; b GSSG = 0.17 ± 0.03 µM/g Hb; c GSH-Px = 19.60 ± 1.96 IU/g Hb; d GSH-Rd = 3.13 ± 0.17 IU/g Hb; e catalase = 394.9 ± 22.8 IU/g Hb; f SOD = 5981 ± 375 IU/g Hb. The addition of 1 to 100 µM Fe3+ had no effect on the parameters analyzed. No change in TBARS levels was detected at any of the iron concentrations studied. Oxidative stress, measured by GSH kinetics over time, occurs when the RBC are incubated with colloidal iron hydroxide at concentrations higher than 10 µM of Fe3+. Overall, these results show that the intact human RBC is prone to oxidative stress when exposed to Fe3+ and that the RBC has a potent antioxidant system that can minimize the potential damage caused by acute exposure to a colloidal iron hydroxide in vitro.

  18. Relation between iron metabolism and antioxidants enzymes and δ-ALA-D activity in rats experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    Bottari, Nathieli B; Mendes, Ricardo E; Baldissera, Matheus D; Bochi, Guilherme V; Moresco, Rafael N; Leal, Marta L R; Morsch, Vera M; Schetinger, Maria R C; Christ, Ricardo; Gheller, Larissa; Marques, Éder J; Da Silva, Aleksandro S

    2016-06-01

    The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (δ-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). δ-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in δ-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in δ-ALA-D activity during chronic phase of disease.

  19. LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

    Directory of Open Access Journals (Sweden)

    Zvi Ioav Cabantchik

    2014-03-01

    Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

  20. N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane (Deofix) - a high-affinity, high-specificity chelator for first transition series metal cations with significant deodorant, antimicrobial, and antioxidant activity.

    Science.gov (United States)

    Laden, Karl; Zaklad, Haim; Simhon, Elliot D; Klein, Joseph Y; Cyjon, Rosa L; Winchell, Harry S

    2003-01-01

    Deofix, N,N',N"-tris(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane, is a high-affinity, high-specificity chelator for first transition series cations such as iron, zinc, manganese, and copper. A 1% solution in 50% ethanol was found to be significantly better at reducing underarm malodor than a solution of 0.3% Triclosan in 50% ethanol. Compared to a 50% alcohol control, Deofix was found to produce a significant reduction in malodor for at least 48 hours. Deofix appears to work by reducing the concentration of first transition series metal ions below the levels needed for microbial cell reproduction and by inhibiting oxidative processes by interfering with catalytic formation of free radicals. Deofix has very low levels of toxicity when measured via a number of screening techniques.

  1. An antioxidant-like action for non-peroxidisable phospholipids using ferrous iron as a peroxidation initiator.

    Science.gov (United States)

    Cortie, Colin H; Else, Paul L

    2015-06-01

    The degradation of phospholipids containing polyunsaturated fatty acids, termed peroxidation, poses a constant challenge to membranes lipid composition and function. Phospholipids with saturated (e.g. PC 16:0/16:0) and monounsaturated fatty acids (e.g. PC 16:0/18:1) are some of the most common phospholipids found in membranes and are generally not peroxidisable. The present experiments show that these non-peroxidisable phospholipids, when present in liposomes with peroxidisable phospholipids (i.e. those containing polyunsaturated fatty acids) such as PC 16:0/18:2 and Soy PC, produce an inhibitory effect on rates of peroxidation induced by ferrous-iron. This inhibitory effect acts to extend the duration of the lag phase by several-fold. If present in natural systems, this action could enhance the capacity of conventional antioxidant mechanisms in membranes. The results of this preliminary work suggest that non-peroxidisable phospholipids may exert an antioxidant-like action in membranes.

  2. Iron-ascorbate-mediated lipid peroxidation causes epigenetic changes in the antioxidant defense in intestinal epithelial cells: impact on inflammation.

    Directory of Open Access Journals (Sweden)

    Sabrina Yara

    Full Text Available INTRODUCTION: The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Intraluminal pro-oxidants from ingested nutrients especially iron salts and ascorbic acid frequently consumed together, can lead to catalytic formation of oxygen-derived free radicals that ultimately overwhelm the cellular antioxidant defense and lead to cell damage. HYPOTHESIS: Since the mechanisms remain sketchy, efforts have been exerted to evaluate the role of epigenetics in modulating components of endogenous enzymatic antioxidants in the intestine. To this end, Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-generating system. RESULTS: Fe/Asc induced a significant increase in lipid peroxidation as reflected by the elevated formation of malondialdehyde along with the alteration of antioxidant defense as evidenced by raised superoxide dismutase 2 (SOD2 and diminished glutathione peroxidase (GPx activities and genes. Consequently, there was an up-regulation of inflammatory processes illustrated by the activation of NF-κB transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IκB. Assessment of promoter's methylation revealed decreased levels for SOD2 and increased degree for GPx2. On the other hand, pre-incubation of Caco-2/15 cells with 5-Aza-2'-deoxycytidine, a demethylating agent, or Trolox antioxidant normalized the activities of SOD2 and GPx, reduced lipid peroxidation and prevented inflammation. CONCLUSION: Redox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.

  3. Exogenous Nitric Oxide Alleviated the Inhibition of Photosynthesis and Antioxidant Enzyme Activities in Iron-Deficient Chinese Cabbage(Brassica chinensis L.)

    Institute of Scientific and Technical Information of China (English)

    DING Fei; WANG Xiu-feng; SHI Qing-hua; WANG Mei-ling; YANG Feng-juan; GAO Qing-hai

    2008-01-01

    The effects of exogenous nitric oxide(NO)on plant growth,chlorophyll contents,photosynthetic and chlorophyll fluorescence parameters as well as lipid peroxidation and activities of antioxidant enzymes were investigated in Chinese cabbage plants exposed to iron(Fe)deficiency.Iron deficiency led to serious chlorosis in Chinese cabbage leaves,and resulted in significant decrease in plant growth,photosynthetic pigments,net photosynthetic rate,Fv/Fm,ΦPsⅡand activities of antioxidant enzymes,and increase in lipid peroxidation.While treatment with SNP,a NO donor,it could revert the iron deficiency symptoms,increased photosynthetic rate as well as activities of antioxidant enzymes,and protected membrane from lipid peroxidation,as a result,the growth inhibition of Chinese cabbage by Fe deficiency was alleviated.

  4. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  5. Iron

    Science.gov (United States)

    ... of iron stored in the body become low, iron deficiency anemia sets in. Red blood cells become smaller and ... from the lungs throughout the body. Symptoms of iron deficiency anemia include tiredness and lack of energy, GI upset, ...

  6. Emblica cascading antioxidant: a novel natural skin care ingredient.

    Science.gov (United States)

    Chaudhuri, Ratan K

    2002-01-01

    A standardized extract of Phyllanthus emblica (trade named Emblica) was found to have a long-lasting and broad-spectrum antioxidant activity. The product has no pro-oxidation activity induced by iron and/or copper because of its iron and copper chelating ability. Emblica helps protect the skin from the damaging effects of free radicals, non-radicals and transition metal-induced oxidative stress. Emblica is suitable for use in anti-aging, sunscreen and general purpose skin care products.

  7. Effect of antioxidant therapy on hepatic fibrosis and liver iron concentrations in β-thalassemia major patients.

    Science.gov (United States)

    Elalfy, Mohsen S; Adly, Amira A M; Attia, Atef A M; Ibrahim, Fatma A; Mohammed, Amer S; Sayed, Abdelbasset M

    2013-01-01

    To assess the effects of combined vitamin therapy on oxidant-antioxidant hepatic status and hemoglobin (Hb) derivatives on β-thalassemia major (β-TM), a prospective study of 60 β-TM patients aged 4 to 17 years, was conducted. Thirty-nine patients with initial low serum vitamins E, C and A, were treated with oral combined vitamins for 1 year compared to 21 patients with normal vitamin levels. Serum transaminases, serum ferritin, hepatic fibroscan elastography (TE) and magnetic resonance imaging R2* (MRI R2*) for liver iron concentration (LIC), were assessed before and after 6 and 12 months of therapy. Antioxidant capacity was assessed by levels of reduced glutathione (GSH), malondialdehyde (MDA), catalase, superoxide dismutase and GSH enzymes. The studied vitamins, reduced GSH and Hb levels were significantly elevated and paralleled by progressive decline in MDA and ferritin during therapy (p 12 kPa) at baseline compared to 20.5% after therapy (p >0.05), although LIC values were significantly decreased (p <0.001). Combined vitamin therapy improves the antioxidant/oxidant balance, LIC and hepatic fibrosis in young β-TM patients.

  8. Antioxidant Activities and Polyphenolic Contents of Three Selected Micromeria Species from Croatia

    Directory of Open Access Journals (Sweden)

    Maja Bival Štefan

    2011-02-01

    Full Text Available Antioxidant activities of three selected Micromeria species growing in Croatia (M. croatica, M. juliana and M. thymifolia were evaluated using five different antioxidant assays, in comparison with plant polyphenolic constituents and reference antioxidants. All studied ethanolic extracts exhibited considerable activity to scavenge DPPH and hydroxyl free radicals, reducing power, iron chelating ability and total antioxidant capacity in the order: M. croatica > M. juliana > M. thymifolia. Total polyphenol (9.69–13.66%, phenolic acid (5.26–6.84%, flavonoid (0.01–0.09% and tannin (3.07–6.48% contents in dried plant samples were determined spectrophotometrically. A strong positive correlation between antioxidant activities and contents of phenolic acids and tannins was found, indicating their responsibility for effectiveness of tested plants. Our findings established Micromeria species as a rich source of antioxidant polyphenols, especially the endemic M. croatica.

  9. Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Satoru Oshiro

    2011-01-01

    Full Text Available Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs. Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD and Parkinson's disease (PD, circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS. Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs.

  10. The Acute Effect of Humic Acid on Iron Accumulation in Rats.

    Science.gov (United States)

    Cagin, Yasir Furkan; Sahin, N; Polat, A; Erdogan, M A; Atayan, Y; Eyol, E; Bilgic, Y; Seckin, Y; Colak, C

    2016-05-01

    Free iron leads to the formation of pro-oxidant reactive oxygen species (ROS). Humic acids (HAs) enhance permeability of cellular wall and act as a chelator through electron transferring. This study was designed to test chelator effect of HA on iron as well as its anti-oxidant effect against the iron-induced hepatotoxicity and cardiotoxicity. The rats used were randomly divided into four groups (n = 8/group): group I (the control group); group II (the HA group), humic acid (562 mg/kg) was given over 10 days by oral gavage; group III (the iron group), iron III hydroxide polymaltose (250 mg/kg) was given over 10 days by intraperitoneal route; and group IV (the HA plus iron group), received the iron (similar to group II) plus humic acid (similar to those in groups II and III) group. Blood and two tissue samples both from liver and heart were obtained for biochemical and histopathological evaluations. Iron deposition, the iron-induced hepatotoxicity, and cardiotoxicity were demonstrated by histopathological and biochemical manner. However, no significant differences were observed in the serum biochemical values and the histopathological results among the iron and the HA plus iron groups in the liver tissue but not in the heart tissue. The protective effects of humic acid against iron-induced cardiotoxicity were shown but not against hepatotoxicity in our study.

  11. Quercetin glycosides and chlorogenic acid in highbush blueberry leaf decoction prevent cataractogenesis in vivo and in vitro: Investigation of the effect on calpains, antioxidant and metal chelating properties.

    Science.gov (United States)

    Ferlemi, Anastasia-Varvara; Makri, Olga E; Mermigki, Penelope G; Lamari, Fotini N; Georgakopoulos, Constantinos D

    2016-04-01

    The present study investigates whether highbush blueberry leaf polyphenols prevent cataractogenesis and the underlying mechanisms. Chlorogenic acid, quercetin, rutin, isoquercetin and hyperoside were quantified in Vaccinium corymbosum leaf decoction (BBL) using HPLC-DAD. Wistar rats were injected subcutaneously with 20 μmol selenite (Na2SeO3)/kg body weight on postnatal (PN) day 10 (Se, n = 8-10/group) only or also intraperitoneally with 100 mg dry BBL/kg body weight on PN days 11 and 12 (SeBBL group, n = 10). Control group received only normal saline (C). Cataract evaluation revealed that BBL significantly prevented lens opacification. It, also, protected lens from selenite oxidative attack and prevented calpain activation, as well as protein loss and aggregation. In vitro studies showed that quercetin attenuated porcine lens turbidity caused by [Formula: see text] or Ca(2+) and interacted efficiently with those ions according to UV-Vis titration experiments. Finally, rutin, isoquercetin and hyperoside moderately inhibited pure human μ-calpain. Conclusively, blueberry leaf extract, a rich source of bioactive polyphenols, prevents cataractogenesis by their strong antioxidant, chelating properties and through direct/indirect inhibition of lens calpains.

  12. Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

    Science.gov (United States)

    Altun, Demet; Kurekci, Ahmet Emin; Gursel, Orhan; Hacıhamdioglu, Duygu Ovunc; Kurt, Ismail; Aydın, Ahmet; Ozcan, Okan

    2014-10-01

    We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.

  13. Inositol hexa phosphoric acid (phytic acid), a nutraceuticals, attenuates iron-induced oxidative stress and alleviates liver injury in iron overloaded mice.

    Science.gov (United States)

    Bhowmik, Anwesha; Ojha, Durbadal; Goswami, Debayan; Das, Rashmi; Chandra, Nidhi S; Chatterjee, Tapan K; Chakravarty, Amit; Chakravarty, Sudipa; Chattopadhyay, Debprasad

    2017-03-01

    Inositol hexa phosphoric acid (IP6) or Phytic acid, a natural antioxidant of some leguminous plants, known to act as a protective agent for seed storage in plants by suppressing iron catalyzed oxidative process. Following the same mechanism, we have tested the effect of IP6 on iron overloaded in vitro oxidative stress, and studied it's in vivo hepatoprotective ability in iron-dextran (injection)-induced iron overloaded liver injury in mice (intraperitoneal). Our results showed that IP6 had in vitro iron chelation (IC50 38.4μg/ml) activity, with the inhibition of iron-induced lipid peroxidation (IC50 552μg/ml), and deoxyribose sugar degrading hydroxyl radicals (IC50 448.6μg/ml). Oral administration of IP6 (0-200mg/kg) revealed significant decrease in biochemical markers such as serum iron, total iron binding, serum ferritin and serum enzymes. Histopathology of liver stained with hematoxylin-eosin and Prussian blue showed reduced hepatocellular necrosis, ballooning and inflammation, indicating the restoration of normal cellular integrity. Interestingly, the IP6 was found to down-regulate the mRNA expression of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 in iron overloaded liver tissues. Thus, we provide an insight that IP6, a natural food component, can serve as an iron chelator against iron overload diseases like Thalassemia, and also as a dietary hepatoprotective supplement.

  14. Green tea or rosemary extract added to foods reduces nonheme- iron absorption

    DEFF Research Database (Denmark)

    Samman, S.; Sandstrøm, B.; Toft, M.B.

    2001-01-01

    the effect of phenolic-rich extracts obtained from green tea or rosemary on nonheme-iron absorption. Design: Young women aged 19-39 y consumed test meals on 4 separate occasions. The meals were identical except for the absence (meal A) or presence (meal B) of a phenolic-rich extract from green tea (study 1......-body retention of 59Fe and the ratio of Fe-55 to 59Fe activity in blood samples. Results: The presence of the phenolic-rich extracts resulted in decreased nonheme-iron absorption. Mean (+/-SD) iron absorption decreased from 12.1 +/- 4.5% to 8.9 +/- 5.2% (P green tea extract and from 7......Background: Phenolic compounds act as food antioxidants. One of the postulated mechanisms of action is chelation of prooxidant metals, such as iron. Although the antioxidative effect is desirable, this mechanism may impair the utilization of dietary iron. Objective: We sought to determine...

  15. 铁螯合剂的应用进展:第53届美国血液学会年会报道%Progress in iron chelators: the report of the 53rd annual meeting of American Society of Hematology

    Institute of Scientific and Technical Information of China (English)

    胡晓静; 侯军; 施菊妹

    2012-01-01

    铁螯合治疗可去除长期输血造成的铁负荷.目前全球有3种可用的螯合剂,即去铁胺、去铁酮和地拉罗司,这些螯合剂可用于单药治疗或联合治疗.在制定最佳、个体化螯合治疗方案时应考虑几个因素,包括螯合剂的可用性和特性、器官特异性的铁负荷程度、输血带来的铁负荷水平以及患者的依从性.疗效比较研究有助于制定理想的治疗方案.本文介绍2011年第53届美国血液学会(ASH)年会关于铁螯合剂应用的研究进展.%Chelation therapy could remove transfusional iron burden. Three chelators are currently available, including deferoxamine, deferiprone, and deferasirox, which can be used as monotherapy or in combination. Several factors must be considered in the design of optimal and individualized chelation regimens,which include chelator availability and its properties,degree of organ-specific iron loading,ongoing transfusional iron burden, and patient preference. Comparative effectiveness trials may help to determine the ideal strategy. This article reviews latest research presented at the 53rd annual meeting of the American Society of Hematology (ASH) on the use of iron chelators.

  16. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    The interest in the role of ferrous iron in diabetes pathophysiology has been revived by recent evidence of iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. The iron metabolism in the β-cell is complex. Excess free iron is toxic......, but at the same time, iron is required for normal β-cell function and thereby glucose homeostasis. In the pathogenesis of diabetes, iron generates reactive oxygen species (ROS) by participating in the Fenton chemistry, which can induce oxidative damage and apoptosis. The aim of this review is to present...... and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...

  17. Fortification with iron chelate and substitution of sucrose by sucralose in light uvaia sherbet (Eugenia pyriformis Cambess): physical, chemical and sensory characteristics.

    Science.gov (United States)

    Giarola, Tales Márcio de Oliveira; Pereira, Cristina Guimarães; de Resende, Jaime Vilela

    2015-09-01

    In this work, iron fortified light uvaia sherbet, with low sucrose content, was developed and its physical, chemical and sensory characteristics were evaluated. The central composite rotational design (CCRD), applicable to the response surface methodology, was used to analyze the formulations. In the formulations, in addition of iron fortification (9 to 15 mg/100 g), the sucrose was substituted by micronized sucralose in a proportion of 66-94 %. The responses were analyzed with respect to changes in pH, total solids, ash, carbohydrates, proteins, calories, overrun, nucleation and thawing temperatures, rheological parameters and sensory attributes. Protein contents and acidity were similar in all formulations. There was a reduction of over 25 % in the caloric value. The rheological results showed pseudoplastic behavior and significant viscosity differences among the tested sherbets. In the overrun and thawing behavior results the sucrose concentration had a significant influence as the formulations with substitution by 28 g of sucralose/kg of sucrose showed greater air incorporation. In the flavor attribute there was not significance in relation to the iron fortification. Sherbets prepared with substitution of sucrose by sucralose and fortified with iron showed good acceptability, more stability and more resistant to thawing.

  18. Brain antioxidant responses to acute iron and copper intoxications in rats.

    Science.gov (United States)

    Semprine, Jimena; Ferrarotti, Nidia; Musacco-Sebio, Rosario; Saporito-Magriñá, Christian; Fuda, Julián; Torti, Horacio; Castro-Parodi, Mauricio; Damiano, Alicia; Boveris, Alberto; Repetto, Marisa G

    2014-11-01

    Dose- and time-dependent antioxidant responses to Fe (0-60 mg kg(-1)) and Cu overloads (0-30 mg kg(-1)) in rat brains are described by the C50 and the t1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50-80%) with a t1/2 of 9-10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C50 for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32-36 μg Fe g(-1) brain and 10-18 μg Cu g(-1) brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46-68% with a t1/2 of 10-11 h and lipophilic antioxidants decreased by 75-45% with a t1/2 of 10-12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100-90% after Fe and Cu loads), with a t1/2 of 8-12 h. GPx-4 activity decreased after both metal loads by 73-27% with a t1/2 of 8-4 h with decreased protein expression.

  19. Antimicrobial and antioxidant activities of Flammulina velutipes polysacchrides and polysacchride-iron(III) complex.

    Science.gov (United States)

    Dong, Ya-Ru; Cheng, Shu-Jie; Qi, Guo-Hong; Yang, Zhi-Ping; Yin, Shi-Yu; Chen, Gui-Tang

    2017-04-01

    FVP is polysacchrides obtained from Flammulina velutipes. A polysacchride named FVP2 was isolated from FVP by DEAE cellulose-52 chromatography and Sephadex G-100 size-exclusion chromatography. FVP-Fe and FVP2-Fe were synthesized by neutralization of FeCl3 carbohydrate solution. The antibacterial and antifungal activities of FVP, FVP2, FVP-Fe, FVP2-Fe were investigated and their antioxidant effects on hydroxyl, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, reducing power, inhibition of malondialdehyde (MDA) were assessed in vitro. The results suggested that FVP-Fe and FVP2-Fe significantly suppressed the growth of bacteria Staphylococcus aureus, Escherichia coli, and Bacillus subtilis, and have relatively strong antioxidant activity to scavenge superoxide anion radical. In addition, FVP exhibited strong antioxidant activity to eliminate hydroxyl, DPPH, ABTS radicals, had high reducing power and inhibited the MDA production of health mice liver homogenate induced by auto-oxidation and Fe(2+)-H2O2 system.

  20. The preparation and antioxidant activity of glucosamine sulfate

    Science.gov (United States)

    Xing, Ronge; Liu, Song; Wang, Lin; Cai, Shengbao; Yu, Huahua; Feng, Jinhua; Li, Pengcheng

    2009-05-01

    Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of chitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O{2/-})/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O{2/-} scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL. Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL. However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.

  1. The preparation and antioxidant activity of glucosamine sulfate

    Institute of Scientific and Technical Information of China (English)

    XING Ronge; LIU Song; WANG Lin; CAI Shengbao; YU Huahua; FENG Jinhua; LI Pengcheng

    2009-01-01

    Glucosamine sulfate was prepared from glucosamine hydrochloride that was produced by acidic hydrolysis of chitin by ion-exchange method. Optical rotation and elemental analysis characterized the degree of its purity. In addition, the antioxidant potency of chitosan derivative-glucosamine sulfate was investigated in various established in vitro systems, such as superoxide (O(2))/hydroxyl (·OH) radicals scavenging, reducing power, iron ion chelating. The following results are obtained: first, glucosamine sulfate had pronounced scavenging effect on superoxide radical. For example the O(2) scavenging activity of glucosamine sulfate was 92.11% at 0.8 mg/mL. Second, the ·OH scavenging activity of glucosamine sulfate was also strong, and was about 50% at 3.2 mg/mL Third, the reducing power of glucosamine sulfate was more pronounced. The reducing power of glucosamine sulfate was 0.643 at 0.75 mg/mL.However, its potency for ferrous ion chelating was weak. Furthermore, except for ferrous ion chelating potency, the scavenging rate of radical and reducing power of glucosamine sulfate were concentration-dependent and increased with their increasing concentrations, but its ferrous ion chelating potency decreased with the increasing concentration. The multiple antioxidant activities of glucosamine sulfate were evidents of reducing power and superoxide/hydroxyl radicals scavenging ability. These in vitro results suggest the possibility that glucosamine sulfate could be used effectively as an ingredient in health or functional food, to alleviate oxidative stress.

  2. The Chelate Effect Redefined.

    Science.gov (United States)

    da Silva, J. J. R. Frausto

    1983-01-01

    Discusses ambiguities of the accepted definition of the chelate effect, suggesting that it be defined in terms of experimental observation rather than mathematical abstraction. Indicates that the effect depends on free energy change in reaction, ligand basicity, pH of medium, type of chelates formed, and concentration of ligands in solution. (JN)

  3. Selective preconcentration/separation of copper(II), iron(III), and lead(II) as their N'-benzoyl-N,N-diisobutylthiourea chelates on Amberlite XAD-16 resin.

    Science.gov (United States)

    Soylak, Mustafa; Kariper, I Afsin

    2010-01-01

    A preconcentration/separation procedure for copper(II), iron(III), and lead(II) ions has been established for use prior to their flame atomic absorption spectrometric determination. The presented procedure is based on adsorption of analyte ions on Amberlite XAD-16 resin as their N'-benzoyl-N,N-diisobutylthiourea chelates. The influence of analytical parameters including pH of the solutions and type of eluent on the recoveries of Cu(II), Fe(III), and Pb(II) ions was investigated. The recoveries of the analytes were generally > 95%. No interference effects were observed from alkaline, earth alkaline, or transition metals on the recoveries of the studied metals. The LODs based on 3sigma were 1.9 microg/L for Cu, 5.9 microg/L for Fe, and 3.1 microg/L for Pb. Validation of the procedure was carried out by analyzing standard reference material 1568a (rice flour). The procedure was applied to the determination of analytes in natural water samples.

  4. Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe(2+)/Cu(2+) Chelator in Cell and Animal Models of Parkinson's Disease.

    Science.gov (United States)

    Aguirre, Pabla; García-Beltrán, Olimpo; Tapia, Victoria; Muñoz, Yorka; Cassels, Bruce K; Núñez, Marco T

    2017-01-18

    Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson's disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu(2+) ∼ Fe(2+) > Zn(2+) > Fe(3+). No binding capacity was detected for Hg(2+), Co(2+), Ca(2+), Mn(2+), Mg(2+), Ni(2+), Pb(2+), or Cd(2+). DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY(581/591). DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetramethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.

  5. Antioxidant properties and efficacies of synthesized alkyl caffeates, ferulates, and coumarates

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit Moltke; Durand, Erwann; Laguerre, Mickaël

    2014-01-01

    Caffeic, ferulic, and coumaric acids were lipophilized with saturated fatty alcohols (C1-C20). The antioxidant properties of these hydroxycinnamic acids and their alkyl esters were evaluated in various assays. Furthermore, the antioxidant efficiency of the compounds was evaluated in a simple o....../w microemulsion using the conjugated autoxidizable triene (CAT) assay. All evaluated phenolipids had radical scavenging, reducing power, and metal chelating properties. Only caffeic acid and caffeates were able to form a complex with iron via their catechol group in the phenolic ring. In the o/w emulsion...

  6. Chelation in metal intoxication—Principles and paradigms

    DEFF Research Database (Denmark)

    Aaseth, Jan; Skaug, Marit Aralt; Cao, Yang;

    2015-01-01

    of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new...... oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review...

  7. BIOACTIVE COMPOUNDS AND ANTIOXIDANT POTENTIAL OF SOY PRODUCTS

    Directory of Open Access Journals (Sweden)

    Beatriz Cervejeira BOLANHO

    2011-12-01

    Full Text Available The aim of this work was to evaluated the amounts of bioactive compounds in soybean and derived products and the antioxidant activity (AA assessed by the methods of ABTS·+ , DPPH· , FRAP and peroxidation of linoleic acid (PLA. The micronized soy protein (MSP, defatted soy flour (DSF and textured soy protein (TSP had a higher content of phenolic compounds and higher antioxidant activity (AA, than the other products. MSP and tofus had the highest content of flavonoids and phytic acid (PA, respectively. The AA correlated with total phenolics and flavonoids, but the PA can act synergistically chelating the pro oxidants ions iron and copper. The highest concentration of copper was in soy protein isolate, and of iron in an ingredient of soy fiber and soy germ. Many compounds present in soy products contribute for the AA, but the concentration and potential will depend on final preparation of the grain or ingredients before consumption.

  8. Effect of iron stress on Withania somnifera L.: antioxidant enzyme response and nutrient elemental uptake of in vitro grown plants.

    Science.gov (United States)

    Rout, Jyoti Ranjan; Behera, Sadhana; Keshari, Nitin; Ram, Shidharth Sankar; Bhar, Subhajit; Chakraborty, Anindita; Sudarshan, Mathummal; Sahoo, Santi Lata

    2015-03-01

    In the present study the response of antioxidant enzyme activities and the level of expression of their corresponding genes on bioaccumulation of iron (Fe) were investigated. In vitro germinated Withania somnifera L. were grown in Murashige and Skoog's liquid medium with increasing concentrations (0, 25, 50, 100 and 200 µM) of FeSO4 for 7 and 14 days. Root and leaf tissues analyzed for catalase (CAT, EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1) and guaiacol peroxidase (GPX, EC 1.11.1.7), have shown an increase in content with respect to exposure time. Isoforms of CAT, SOD and GPX were separated using non-denaturing polyacrylamide gel electrophoresis and observed that the isoenzymes were greatly affected by higher concentrations of Fe. Reverse transcriptase polymerase chain reaction analysis performed by taking three pairs of genes of CAT (RsCat, Catalase1, Cat1) and SOD (SodCp, TaSOD1.2, MnSOD) to find out the differential expression of antioxidant genes under Fe excess. RsCat from CAT and MnSOD from SOD have exhibited high levels of gene expression under Fe stress, which was consistent with the changes of the activity assayed in solution after 7 days of treatment. Analysis by proton induced X-ray emission exhibited an increasing uptake of Fe in plants by suppressing and expressing of other nutrient elements. The results of the present study suggest that higher concentration of Fe causes disturbance in nutrient balance and induces oxidative stress in plant.

  9. 复合氨基酸络合铁、锌对肥育猪铁、锌吸收代谢的影响%Effects of Iron and Zinc Complex Amino Acid Chelate on Absorption Metabolism of Iron and Zinc of Finishing Pigs

    Institute of Scientific and Technical Information of China (English)

    詹康; 占今舜; 赵国琦; 霍永久

    2014-01-01

    本试验旨在研究复合氨基酸络合铁、锌对肥育猪血液生化指标,血清中免疫球蛋白含量,毛发中铁、锌含量及铁、锌表观消化率的影响。选择体重[(55.63±1.33)kg]相近的“杜×长×大”肥育猪36头,随机分至对照组和2个试验组,每组3个重复,每个重复4头猪。对照组饲喂铁、锌含量均为100 mg/kg(由硫酸亚铁、硫酸锌提供)的基础饲粮,试验1组饲喂铁、锌含量均为50 mg/kg(由硫酸亚铁、硫酸锌提供)+50 mg/kg(由复合氨基酸络合铁、锌提供)的基础饲粮,试验2组饲喂铁、锌含量均为100 mg/kg(由复合氨基酸络合铁、锌提供)的基础饲粮。结果表明:1)3组间的红细胞数量、血细胞压积、血清免疫球蛋白A和免疫球蛋白M含量无显著差异( P>0.05)。2)试验2组的血红蛋白含量和血清免疫球蛋白 G含量显著高于对照组( P<0.05)。3)试验2组毛发中铁含量显著高于对照组( P<0.05),试验2组毛发中锌含量显著高于试验1组和对照组( P<0.05);4)试验2组粪中铁含量和试验2组、试验1组粪中锌含量显著低于对照组( P<0.05);3组间铁和锌表观消化率无显著差异( P>0.05)。由此可见,添加复合氨基酸络合铁、锌可显著增加肥育猪血红蛋白、血清免疫球蛋白G含量及毛发中铁、锌含量,显著降低粪中铁、锌含量。%To study the effects of iron and zinc complex amino acid chelate on blood biochemical indexes,im-munoglobulin content in serum,iron and zinc contents in hair and apparent digestibility of iron and zinc of fin-ishing pigs,thirty-six finishing pigs( Duroc × Landrace × Yorkshire ) with an average initial body weight of (55.63±1.33)kg were selected and randomly allotted to three groups. There were three replicates per group and four pigs in each replicate. Pigs of the control group fed a basal diet with 100 mg

  10. Salmonella proteomics under oxidative stress reveals coordinated regulation of antioxidant defense with iron metabolism and bacterial virulence.

    Science.gov (United States)

    Fu, Jiaqi; Qi, Linlu; Hu, Mo; Liu, Yanhua; Yu, Kaiwen; Liu, Qian; Liu, Xiaoyun

    2017-02-11

    Salmonella Typhimurium is a bacterial pathogen that can cause widespread gastroenteritis. Salmonella encounters reactive oxygen species both under free-living conditions and within their mammalian host during infection. To study its response to oxidative stress, we performed the first large-scale proteomic profiling of Salmonella upon exposure to H2O2. Among 1600 detected proteins, 83 proteins showed significantly altered abundance. Interestingly, only a subset of known antioxidants was induced, likely due to distinct regulatory mechanisms. In addition, we found elevation of several Salmonella acquired phage products with potential contribution to DNA repair under oxidative stress. Furthermore, we observed robust induction of iron-uptake systems and disruption of these pathways led to bacterial survival defects under H2O2 challenge. Importantly, this work is the first to report that oxidative stress severely repressed the Salmonella type III secretion system (T3SS), reducing its virulence. Biological significance Salmonella, a Gram-negative bacterial pathogen, encounters reactive oxygen species (ROS) both endogenously and exogenously. To better understand its response to oxidative stress, we performed the first large-scale profiling of Salmonella protein expression upon H2O2 treatment. Among 1600 quantified proteins, the abundance of 116 proteins was altered significantly. Notably, iron acquisition systems were induced to promote bacterial survival under oxidative stress. Furthermore, we are the first to report that oxidative stress severely repressed Salmonella type III secretion system and hence reduced its virulence. We believe that these findings will not only help us better understand the molecular mechanisms that Salmonella has evolved to counteract ROS but also the global impact of oxidative stress on bacterial physiology.

  11. $\\beta$-Caseinophosphopeptide (f1-25) confers on $\\beta$-casein tryptic hydrolysate an antioxidant activity during iron/ascorbate-induced oxidation of liposomes

    OpenAIRE

    2004-01-01

    International audience; Protein ingredients such as hydrolysates of milk proteins may improve the nutritive value of functional foods. For instance, $\\beta$-casein tryptic hydrolysate could simultaneously increase iron absorption and prevent lipid oxidation in foods containing high contents of polyunsaturated fatty acids (PUFA). The aim of this study was to determine the antioxidant activity of $\\beta$-casein tryptic hydrolysate and of its $\\beta$-caseinophosphopeptide (f1-25) on Fe(III)/asco...

  12. Metal based pharmacologically active agents: Synthesis, structural characterization, molecular modeling, CT-DNA binding studies and in vitro antimicrobial screening of iron(II) bromosalicylidene amino acid chelates

    Science.gov (United States)

    Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.; Ismael, Mohamed; Seleem, Amin Abdou

    2014-01-01

    In recent years, great interest has been focused on Fe(II) Schiff base amino acid complexes as cytotoxic and antitumor drugs. Thus a series of new iron(II) complexes based on Schiff bases amino acids ligands have been designed and synthesized from condensation of 5-bromosalicylaldehyde (bs) and α-amino acids (L-alanine (ala), L-phenylalanine (phala), L-aspartic acid (aspa), L-histidine (his) and L-arginine (arg)). The structure of the investigated iron(II) complexes was elucidated using elemental analyses, infrared, ultraviolet-visible, thermogravimetric analysis, as well as conductivity and magnetic susceptibility measurements. Moreover, the stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically. The results suggest that 5-bromosalicylaldehyde amino acid Schiff bases (bs:aa) behave as dibasic tridentate ONO ligands and coordinate to Fe(II) in octahedral geometry according to the general formula [Fe(bs:aa)2]ṡnH2O. The conductivity values between 37 and 64 ohm-1 mol-1 cm2 in ethanol imply the presence of nonelectrolyte species. The structure of the complexes was validated using quantum mechanics calculations based on accurate DFT methods. Geometry optimization of the Fe-Schiff base amino acid complexes showed that all complexes had octahedral coordination. In addition, the interaction of these complexes with (CT-DNA) was investigated at pH = 7.2, by using UV-vis absorption, viscosity and agarose gel electrophoresis measurements. Results indicated that the investigated complexes strongly bind to calf thymus DNA via intercalative mode and showed a different DNA binding according to the sequence: bsari > bshi > bsali > bsasi > bsphali. Moreover, the prepared compounds are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus

  13. ANTIOXIDANT MUSHROOMS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Aggarwal Preeti

    2012-06-01

    Full Text Available The antioxidant properties of wild mushrooms have been extensively studied and many antioxidant compounds such as phenolic compounds, tocopherols, ascorbic acid, and carotenoids identified. The various antioxidant mechanisms of the mushroom species extracts may be attributed to strong hydrogen-donating ability, metal-chelating ability, and their effectiveness as good scavengers of superoxide and free radicals. This indicates the potential of mushrooms as panacea for many diseases and also reveals a novel potential to fight against tumors in man.

  14. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  15. Treatment of chelated copper in EDTA solution by iron chip inner-electrolysis%铁屑内电解法处理EDTA溶液中络合铜离子

    Institute of Scientific and Technical Information of China (English)

    鞠峰; 胡勇有; 程建华; 伍健东

    2011-01-01

    采用批式试验和现代仪器分析研究了铁屑内电解法处理EDTA溶液中络合铜离子,考察了溶液浓度、溶液pH、温度和铁屑粒径等因素对铜离子去除过程的影响.结果表明,铜离子去除过程符合表观一级动力学方程.在pH 2.0~11.0范围内,pH值越低越利于铜离子去除;在酸性条件下溶液pH随内电解进行升高,在碱性条件下溶液pH随内电解进行降低.EDTA络合铜浓度过高和铁屑粒径过大都不利于铜离子去除.在288~318 K范围内,提高温度可提高反应速率;表观反应活化能为26.57 kJ·mol-1,反应过程受化学反应控制.经铁屑内电解法处理后EDTA络合铜最终转变为Fe(Ⅲ)-EDTA,该过程涉及铁屑置换还原,铁离子置换沉淀作用,电附集和吸附共沉淀等作用.%The removal of copper from EDTA solution by iron chip inner-electrolysis was studied using a hatch method and modem instruments. The effects of EDTA-Cu concentration, solution pH, reaction temperature and iron chip diameter on copper removal were investigated. The results showed that chelated copper removal by iron chip inner-electrolysis followed pseudo first-order kinetics. In the pH range of 2.0 - 11. O, lower solution pH was favorable for copper removal; solution pH increased over time under acidic conditions, and decreased over time under alkaline conditions. Too high EDTA-Cu concentration and too large iron diameter were disadvantageous to copper removal. At the reaction temperature of 288 ~ 318 K, increased temperature led to faster copper removal. The apparent activation energy was 26.57 kJ · mol - 1, indicating that copper removal was controlled by a chemical process. After treatment by iron chip inner-electrolysis, Cu-EDTA was converted into Fe( Ⅲ )-EDTA, and this process involved the combined effects of Fe3 + replacement-precipitation, Fe0 replacement & reduction, electro-deposition, adsorption and co-precipitation.

  16. Combination of Antioxidants from Different Sources Could Offer Synergistic Benefits: A Case Study of Tea and Ginger Blend.

    Science.gov (United States)

    Makanjuola, Solomon A; Enujiugha, Victor N; Omoba, Olufunmilayo S; Sanni, David M

    2015-11-01

    Tea and ginger are plants with high antioxidant potential. Combinations of antioxidants from different sources could also produce synergistic antioxidant effects. This study investigated the influence of solvent on antioxidant content of tea, ginger, and tea + ginger blends. Under the investigated extraction conditions, water was the most effective extraction solvent to maximise peroxide scavenging and iron chelating activity of tea, ginger, and their blends. Aqueous ethanol was the most effective solvent to maximise ABTS radical scavenging activity and ethanol was the best solvent to maximise DPPH radical scavenging activity. A good multivariate regression model that explains the relationship between the total flavonoid content of the extracts and their antioxidant activities was obtained (R2 and Q2 of 0.93 and 0.83, respectively). Extracts of tea-ginger blends exhibited synergistic effects in their ABTS and DPPH radical scavenging activity.

  17. Nanoparticle and other metal chelation therapeutics in Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Garrett, Matthew R; Men, Ping; Zhu, Xiongwei; Perry, George; Smith, Mark A

    2005-09-25

    Current therapies for Alzheimer disease (AD) such as the anticholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of disease, but do not arrest disease progression or supply meaningful remission. As such, new approaches to disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. In this review, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show a unique ability to cross the blood-brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may prove to be a safe and effective means of reducing the metal load in neural tissue thus staving off the harmful effects of oxidative damage and its sequelae.

  18. Simulated gastrointestinal pH condition improves antioxidant properties of wheat and rice flours.

    Science.gov (United States)

    Chan, Kim Wei; Khong, Nicholas M H; Iqbal, Shahid; Ismail, Maznah

    2012-01-01

    The present study was conducted to evaluate the antioxidant properties of wheat and rice flours under simulated gastrointestinal pH condition. After subjecting the wheat and rice flour slurries to simulated gastrointestinal pH condition, both slurries were centrifuged to obtain the crude phenolic extracts for further analyses. Extraction yield, total contents of phenolic and flavonoids were determined as such (untreated) and under simulated gastrointestinal pH condition (treated). 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(•)) scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS(•+)) scavenging activity, ferric reducing antioxidant power (FRAP), beta-carotene bleaching (BCB) and iron chelating activity assays were employed for the determination of antioxidant activity of the tested samples. In almost all of the assays performed, significant improvements in antioxidant properties (p properties might be improved under gastrointestinal digestive conditions.

  19. Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity.

    Science.gov (United States)

    Vallelian, Florence; Schaer, Christian A; Kaempfer, Theresa; Gehrig, Peter; Duerst, Elena; Schoedon, Gabriele; Schaer, Dominik J

    2010-12-09

    Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb.

  20. Chelation Therapy for Mercury Poisoning

    Directory of Open Access Journals (Sweden)

    Rong Guan

    2009-01-01

    Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

  1. Fixation kinetics of chelated and non-chelated zinc in semi-arid alkaline soils: application to zinc management

    Science.gov (United States)

    Udeigwe, Theophilus K.; Eichmann, Madeleine; Menkiti, Matthew C.

    2016-07-01

    This study was designed to examine the fixation pattern and kinetics of zinc (Zn) in chelated (ethylenediaminetetraacetic acid, EDTA) and non-chelated mixed micronutrient systems of semi-arid alkaline soils from the Southern High Plains, USA. Soils were characterized for a suite of chemical and physical properties and data obtained from extraction experiments fitted to various kinetic models. About 30 % more plant-available Zn was fixed in the non-chelated system within the first 14 days with only about 18 % difference observed between the two systems by day 90, suggesting that the effectiveness of the chelated compounds tended to decrease over time. The strengths of the relationships of change in available Zn with respect to other micronutrients (copper, iron, and manganese) were higher and more significant in the non-chelated system (average R2 of 0.83), compared to the chelated (average R2 of 0.42). Fixation of plant-available Zn was best described by the power-function model (R2 = 0.94, SE = 0.076) in the non-chelated system, and was poorly described by all the models examined in the chelated system. Reaction rate constants and relationships generated from this study can serve as important tools for micronutrient management and for future micronutrient modeling studies on these soils and other semi-arid regions of the world.

  2. Total antioxidant capacity, total phenolic content and iron and zinc dialyzability in selected Greek varieties of table olives, tomatoes and legumes from conventional and organic farming.

    Science.gov (United States)

    Drakou, Marina; Birmpa, Angeliki; Koutelidakis, Antonios E; Komaitis, Michael; Panagou, Efstathios Z; Kapsokefalou, Maria

    2015-03-01

    The objective was to compare 10 types of table olives, 11 types of tomatoes and tomato products and 18 types of legumes from conventional or organic farming for selected nutritional properties. All products were tested for their total antioxidant capacity (TAC) (Ferric Reducing Antioxidant Power (FRAP) assay) and total phenolic content (Folin-Ciocalteau method). Tomatoes and legumes were further tested for iron and zinc dialyzability after in vitro digestion. Ascorbic acid content of tomatoes was also measured. The study resulted that the nutritional properties of olives, tomatoes and legumes tested were different among the various cultivars but, in most cases, not between products from organic or conventional farming. Natural black olives, cherry and santorini tomatoes and lentils exhibited superior nutritional properties.

  3. MRI marrow observations in thalassemia: the effects of the primary disease, transfusional therapy, and chelation

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States); Abramson, S. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Piomelli, S. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital, New York, NY (United States)

    1995-11-01

    The magnetic resonance bone marrow patterns in thalassemia were evaluated to determine changes produced by transfusion and chelation therapy. Thirteen patients had T1- and T2-weighted images of the spine, pelvis and femurs. Three received no therapy (age range 2.5-3 years). Three were ``hypertransfused`` (transfused to maintain a hemoglobin greater than 10 g/dl) and not chelated because of age (age range 6 months-8 years). Seven were ``hypertransfused`` and chelated (age range 12-35 years). Signal characteristics of marrow were compared with those of surrounding muscle and fat. Fatty marrow (isointense with subcutaneous fat) was compared with red marrow (hypointense to fat and slightly hyperintense to muscle). Marrow hypointense to muscle was identified as iron deposition within red marrow. The untreated group demonstrated signal consistent with red marrow throughout the central and peripheral skeleton. Hypertransfused but not chelated patients demonstrated marked iron deposition in the central and peripheral skeleton. Hypertransfused and chelated patients demonstrated iron deposition in the central skeleton and a mixed appearance of marrow in the peripheral skeleton. The MR appearance of marrow in thalassemia is a reflection of the patient`s transfusion and chelation therapy. Iron deposition occurs despite chelation therapy in sites of active red marrow. As red marrow retreats centrally with age, so does the pattern of iron deposition. The long-term biological effects of this iron deposition are unknown. (orig.). With 8 figs., 1 tab.

  4. Chelation Therapy for Mercury Poisoning

    OpenAIRE

    Rong Guan; Han Dai

    2009-01-01

    Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role o...

  5. MULTIDENTATE TEREPHTHALAMIDATE AND HYDROXYPYRIDONATE LIGANDS: TOWARDS NEW ORALLY ACTIVE CHELATORS

    Energy Technology Data Exchange (ETDEWEB)

    Abergel, Rebecca J.; Raymond, Kenneth N.

    2011-07-13

    The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using {sup 59}Fe, {sup 238}Pu, and {sup 241}Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.

  6. Metal chelate process to remove pollutants from fluids

    Science.gov (United States)

    Chang, Shih-Ger T.

    1994-01-01

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO.sub.x and optionally SO.sub.2 from a fluid using a metal ion (Fe.sup.2+) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC' is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution.

  7. Metal chelate process to remove pollutants from fluids

    Science.gov (United States)

    Chang, S.G.T.

    1994-12-06

    The present invention relates to improved methods using an organic iron chelate to remove pollutants from fluids, such as flue gas. Specifically, the present invention relates to a process to remove NO[sub x] and optionally SO[sub 2] from a fluid using a metal ion (Fe[sup 2+]) chelate wherein the ligand is a dimercapto compound wherein the --SH groups are attached to adjacent carbon atoms (HS--C--C--SH) or (SH--C--CCSH) and contain a polar functional group so that the ligand of DMC chelate is water soluble. Alternatively, the DMC is covalently attached to a water insoluble substrate such as a polymer or resin, e.g., polystyrene. The chelate is regenerated using electroreduction or a chemical additive. The dimercapto compound bonded to a water insoluble substrate is also useful to lower the concentration or remove hazardous metal ions from an aqueous solution. 26 figures.

  8. Studies on the antioxidant activities of Desmodium gangeticum.

    Science.gov (United States)

    Govindarajan, Raghavan; Rastogi, Subha; Vijayakumar, Madhavan; Shirwaikar, Annie; Rawat, Ajay Kumar Singh; Mehrotra, Shanta; Pushpangadan, Palpu

    2003-10-01

    Desmodium gangeticum is herbal species which is widely used in the indigenous system of medicine and is reported to contain flavone and isoflavanoid glycosides. In view of its wide use and it's chemical composition, this study was aimed at examining the antioxidant activity of the extract of D. gangeticum. The extract was studied for diphenyl picryl hydrazyl (DPPH), nitric oxide, ferryl-bipyridyl and hypochlorous acid scavenging activity along with lipid peroxidation. Nitric oxide was generated using sodium nitroprusside and was studied using Griess reagent. In order to study the iron chelating capacity of the extract, the percentage ferryl-bipyridyl inhibition was studied. Hypochlorous acid scavenging activity was tested by measuring the inhibition of 5-thio-2-nitrobenzoic acid oxidation. The extract was also studied for lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat brain homogenate. The results indicate that D. gangeticum extract has potent antioxidant activity.

  9. Reductive iron assimilation and intracellular siderophores assist extracellular siderophore-driven iron homeostasis and virulence

    Science.gov (United States)

    Iron is an essential nutrient and prudent iron acquisition and management are key traits of a successful pathogen. Fungi use nonribosomally synthesized secreted iron chelators (siderophores) or Reductive Iron Assimilation (RIA) mechanisms to acquire iron in a high affinity manner. Previous studies...

  10. Rapid reductive degradation of aqueous p-nitrophenol using nanoscale zero-valent iron particles immobilized on mesoporous silica with enhanced antioxidation effect

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Lin, E-mail: tanglin@hnu.edu.cn [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Tang, Jing [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Zeng, Guangming, E-mail: zgming@hnu.edu.cn [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Yang, Guide; Xie, Xia; Zhou, Yaoyu [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Pang, Ya [Department of Biological Engineering and Environmental Science, Changsha College, Changsha 410003 (China); Fang, Yan; Wang, Jiajia [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Xiong, Weiping [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China)

    2015-04-01

    Highlights: • Nanoscale zero-valent iron (nZVI) was doped in mesoporous silica (SBA-15). • High capacity and fast rate for the removal of p-nitrophenol. • Better antioxidant ability of nZVI/SBA-15 than nZVI. • p-Nitrophenol removal depended heavily on immobilized nZVI amount. • Mechanism of PNP removal by nZVI/SBA-15 was proposed. - Abstract: In this study, nanoscale zero-valent iron particles immobilized on mesoporous silica (nZVI/SBA-15) were successfully prepared for effective degradation of p-nitrophenol (PNP). The nZVI/SBA-15 composites were characterized by N{sub 2} adsorption/desorption, transmission electron microscopy (TEM), UV–vis spectrum and X-ray photoelectron spectroscopy (XPS). Results showed that abundant ultrasmall nanoscale zero-valent iron particles were formed and well dispersed on mesoporous silica (SBA-15). Batch experiments revealed that PNP removal declined from 96.70% to 16.14% as solution pH increased from 3.0 to 9.0. Besides, degradation equilibrium was reached within 5 min, which was independent of initial PNP concentration. Furthermore, only a little PNP elimination on SBA-15 indicated that nZVI immobilized on mesoporous silica was mainly responsible for the target contaminant removal. The UV–vis spectrum and XPS measurement confirmed that the PNP removal was a reductive degradation process, which was further proved by the detected intermediates using gas chromatography–mass spectrometry (GC/MS). The excellent antioxidation ability had been discovered with more than 80% of PNP being removed by nZVI/SBA-15 treated with 30 days’ exposure to air. These results demonstrated the feasible and potential application of nZVI/SBA-15 composites in organic wastewater treatment.

  11. Efficient solvent extraction of antioxidant-rich extract from a tropical diatom,Chaetoceros calcitrans (Paulsen) Takano 1968简

    Institute of Scientific and Technical Information of China (English)

    Su; Chern; Foo; Fatimah; Md.Yusoff; Maznah; Ismail; Mahiran; Basri; Nicholas; Mun; Hoe; Khong; Kim; Wei; Chan; Sook; Kun; Yau

    2015-01-01

    Objective: To compare the in vitro antioxidant capacity of a diatom, Chaetoceros calcitrans(C. calcitrans) extracted using six types of solvents.Methods: Each extract was evaluated in terms of extraction yield, total carotenoid,fucoxanthin content, total phenolic and antioxidant capacities(DPPH and ABTS +scavenging activity and iron chelating activity).Results: The methanol extract exhibited the highest yield [(22.71 ± 0.96) g/100 g dry weight(DW)], total carotenoid [(4.46 ± 0.36) mg/g DW], total phenolic [(2.49 ± 0.08) mg gallic acid equivalents/g DW] and second highest fucoxanthin content [(2.08 ± 0.03) mg fucoxanthin/g DW] as compared to other solvent extracts. Methanolic extract also exhibited significantly higher(P < 0.05) scavenging(DPPH, ABTS +) and iron chelating activities.Conclusions: Methanol was the recommended solvent for the production of antioxidant rich extract from C. calcitrans. Both carotenoids and phenolic acids were found to be positively correlated to the antioxidant capacities of C. calcitrans. Lead bioactives confirmed by subsequent high performance liquid chromatography studies were fucoxanthin, gallic acid and protocatechuic acid.

  12. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  13. Chelated minerals for poultry

    Directory of Open Access Journals (Sweden)

    SL Vieira

    2008-06-01

    Full Text Available Organic minerals have been subject of an increasing number of investigations recently. These compounds can be considered the most significant event regarding commercial forms of minerals targeting animal supplementation in the last decades. Minerals, especially metals, are usually supplemented in poultry feeds using cheap saline sources and have never required a lot of attention in terms of quality. On the other hand, definitions of organic minerals are very broad and frequently lead to confusion when decision-making becomes necessary. Organic minerals include any mineral bound to organic compounds, regardless of the type of existing bond between mineral and organic molecules. Proteins and carbohydrates are the most frequent candidates in organic mineral combinations. Organic fraction size and bond type are not limitations in organic mineral definition; however, essential metals (Cu, Fe, Zn, and Mn can form coordinated bonds, which are stable in intestinal lumen. Metals bound to organic ligands by coordinated bonds can dissociate within animal metabolism whereas real covalent bonds cannot. Chelated minerals are molecules that have a metal bound to an organic ligand through coordinated bonds; but many organic minerals are not chelates or are not even bound through coordinated bonds. Utilization of organic minerals is largely dependent on the ligand; therefore, amino acids and other small molecules with facilitated access to the enterocyte are supposed to be better utilized by animals. Organic minerals with ligands presenting long chains may require digestion prior to absorption. After absorption, organic minerals may present physiological effects, which improve specific metabolic responses, such as the immune response. Many studies have demonstrated the benefits of metal-amino acid chelates on animal metabolism, but the detection positive effects on live performance is less consistent.

  14. Analgesic and Antioxidant Activities of Stem Bark Extract and Fractions of Petersianthus macrocarpus

    Science.gov (United States)

    Orabueze, Celestina Ifeoma; Adesegun, Sunday Adeleke; Coker, Herbert Alexander

    2016-01-01

    Background: Petersianthus macrocarpus (Lecythidaceae) is widely used in the folk medicine in Nigeria to relieve pain and fever associated with malaria. This study evaluated the analgesic and antioxidant activities of the methanol extract and fractions of the stem bark of the plant. Materials and Methods: The analgesic activity was determined in mice using hotplate and acetic acid-induced writhing models. Morphine sulphate (5 mg/kg, i.p.) and aspirin (100 mg/ml, p.o.) were used as reference analgesic agents. The antioxidant potential was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical; reducing power, iron chelating properties and determination of total phenolic content. Results: The extract at 200 and 500 mg/kg, produced an insignificant (P > 0.05) increase in pain threshold in hotplate but a significant (P < 0.05) increase at 1000 mg/kg. The extract significantly (P < 0.05) reduced the writhing induced by acetic acid in mice in a dose dependent manner. Fractionation increased the analgesic activities significantly (P < 0.05) in ethyl acetate and aqueous fractions (200 mg/kg). The extract demonstrated strong DPPH radical scavenging activity with IC50 0.05 mg/ml, good reducing power and weak iron chelating activities. The total phenol content was 142.32 mg/gin term of gallic acid. The antioxidant effects were more pronounced in ethyl acetate and aqueous fractions. Conclusion: The findings of the study suggested that the extract has strong analgesic and antioxidant activities which reside mainly in the polar fractions thus confirming the traditional use of the plant to alleviate pains. SUMMARY Analgesic and antioxidant activities of extract and solvent fractions of Petersianthus macrocarpus investigated indicated that extract has analgesic and antioxidant properties that reside mainly in the polar fractions. Abbreviations Used: DMSO: Dimethyl sulphoxide, ANOVA: analysis of variance, EDTA: ethylene diamne tetraacetic acid, SDM: standard deviation of mean

  15. Combined Chelation Therapy with Deferasirox and Deferoxamine in Thalassemia

    OpenAIRE

    Lal, Ashutosh; Porter, John; Sweeters, Nancy; Ng, Vivian; Evans, Patricia; Neumayr, Lynne; Kurio, Gregory; Harmatz, Paul; Vichinsky, Elliott

    2012-01-01

    Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50 mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9...

  16. Chelation of aluminum by combining deferasirox and deferiprone in rats.

    Science.gov (United States)

    Saljooghi, Amir Shokooh

    2012-09-01

    The hypothesis that two known chelators deferasirox and deferiprone (L1) might be more efficient as combined treatment than as single therapies in removing aluminum from the body was tested in a new acute rat model. Seven-week-old male Wistar rats received chelators: deferasirox (orally [p.o.]), L1 (p.o.) or deferasirox + L1 as 100 or 200 mg/kg dose half an hour after a single intraperitoneal administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminum concentration, urinary aluminum and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While deferasirox was more effective than L1 in enhancing urinary aluminum excretion, L1 was more effective than deferasirox in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the L1 effect on aluminum and L1 did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminum chelators. Urinary values were more useful due to the high variability of serum results.

  17. Influence of silymarin and its flavonolignans on doxorubicin-iron induced lipid peroxidation in rat heart microsomes and mitochondria in comparison with quercetin.

    Science.gov (United States)

    Psotová, Jitka; Chlopcíková, Sárka; Grambal, Frantisek; Simánek, Vilím; Ulrichová, Jitka

    2002-03-01

    Silymarin, an extract of Silybum marianum seeds, and the constituent flavonolignans silybin, silydianin and silychristin, as well as the flavonol quercetin, protected rat heart microsomes and mitochondria against iron-dependent doxorubicin induced lipid peroxidation. Quercetin was found to be more potent than either silymarin or its three constituents, whose cytoprotectivity was comparable. The radical scavenging activity of the compounds was investigated using a DPPH colour reduction assay and cyclic voltametry to assess their antioxidant activities. In contrast to quercetin, silybin, silydianin and silychristin did not chelate iron in aqueous solution. The results suggest that silymarin may prevent doxorubicin-mediated damage to rat heart membrane primarily through a free radical scavenging mechanism.

  18. Nitroaryl-1,4-dihydropyridines as antioxidants against rat liver microsomes oxidation induced by iron/ascorbate, nitrofurantoin and naphthalene.

    Science.gov (United States)

    Letelier, María Eugenia; Entrala, Paz; López-Alarcón, Camilo; González-Lira, Víctor; Molina-Berríos, Alfredo; Cortés-Troncoso, Juan; Jara-Sandoval, José; Santander, Paola; Núñez-Vergara, Luis

    2007-12-01

    1,4-Dihydropyridines (DHPs) used in the treatment of cardiovascular diseases, are calcium channel antagonists and also antioxidant agents. These drugs are metabolized through cytochrome P(450) oxidative system, majority localized in the hepatic endoplasmic reticulum. Several lipophilic drugs generate oxidative stress to be metabolized by this cellular system. Thus, DHP antioxidant properties may prevent the oxidative stress associated with hepatic biotransformation of drugs. In this work, we tested the antioxidant capacity of several synthetic nitro-phenyl-DHPs. These compounds (I-IV) inhibited the microsomal lipid peroxidation, UDPGT oxidative activation and microsomal thiols oxidation; all phenomena induced by Fe(3+)/ascorbate, a generator system of oxygen free radicals. As the same manner, these compounds inhibited the oxygen consumption induced by Cu(2+)/ascorbate in the absence of microsomes. Furthermore, compound III (2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridin-3,5-ethyl-dicarboxylate) and compound V (N-ethyl-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridin-3,5-methyl-dicarboxylate) inhibited the microsomal lipid peroxidation induced by Nitrofurantoin and naphthalene in the presence of NADPH. Oxidative stress induced on endoplasmic reticulum may alter the biotransformation of drugs, so, modifying their plasmatic concentrations and therapeutic effects. When drugs which are activated by biotransformation are administered together with antioxidant drugs, such as DHPs, oxidative stress induced in situ may be prevented.

  19. Examining the fixation kinetics of chelated and non-chelated copper and the applications to micronutrient management in semiarid alkaline soils

    Science.gov (United States)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.; Kusi, N. Y. O.

    2016-02-01

    This study examined and compared the fixation and fixation kinetics of copper (Cu) in chelated (ethylene diamine tetraacetic acid, EDTA) and non-chelated mixed systems of micronutrients in the semiarid soils of the Southern High Plains, USA, using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system compared to the chelated within the first 14 days with only 7 % difference between the two systems by day 90. Findings suggest a decrease in the effectiveness of chelated micronutrients over time, highlighting the significance of timing even when chelated micronutrients are used. The strengths of the relationship of change in available Cu with respect to other micronutrients (iron (Fe), manganese (Mn), and zinc (Zn)) were higher in the non-chelated system (R2: 0.68-0.94), compared to the chelated (R2: 0.42-0.81), with slopes of 0.40 (Cu-Fe), 0.31 (Cu-Mn), and 1.04 (Cu-Zn) in the non-chelated system and 0.26 (Cu-Fe), 0.22 (Cu-Mn), and 0.90 (Cu-Zn) in the chelated system. Reduction in the amount of available Cu was best described by the power function model (R2 = 0.91, SE = 0.081) in the non-chelated system and second-order model (R2 = 0.95, SE = 0.010) in the chelated system. The applications generated from this study could be used as tools for improved micronutrient management and also provide baseline data for future work in other semiarid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  20. Macroreticular chelating ion-exchangers.

    Science.gov (United States)

    Hirsch, R F; E Gancher, R; Russo, F R

    1970-06-01

    Two macroreticular chelating ion-exchangers have been prepared and characterized. One contains the iminodiacetate group and the second contains the arsonate group as the ion-exchanging site. The macroreticular resins show selectivities among metal ions similar to those of the commercially available naicroreticular chelating resins. Chromatographie separations on the new resins are rapid and sharp.

  1. Efficacy of chelation therapy to remove aluminium intoxication.

    Science.gov (United States)

    Fulgenzi, Alessandro; De Giuseppe, Rachele; Bamonti, Fabrizia; Vietti, Daniele; Ferrero, Maria Elena

    2015-11-01

    There is a distinct correlation between aluminium (Al) intoxication and neurodegenerative diseases (ND). We demonstrated how patients affected by ND showing Al intoxication benefit from short-term treatment with calcium disodium ethylene diamine tetraacetic acid (EDTA) (chelation therapy). Such therapy further improved through daily treatment with the antioxidant Cellfood. In the present study we examined the efficacy of long-term treatment, using both EDTA and Cellfood. Slow intravenous treatment with the chelating agent EDTA (2 g/10 mL diluted in 500 mL physiological saline administered in 2 h) (chelation test) removed Al, which was detected (using inductively coupled plasma mass spectrometry) in urine samples collected from patients over 12 h. Patients that revealed Al intoxication (expressed in μg per g creatinine) underwent EDTA chelation therapy once a week for ten weeks, then once every two weeks for a further six or twelve months. At the end of treatment (a total of 22 or 34 chelation therapies, respectively), associated with daily assumption of Cellfood, Al levels in the urine samples were analysed. In addition, the following blood parameters were determined: homocysteine, vitamin B12, and folate, as well as the oxidative status e.g. reactive oxygen species (ROS), total antioxidant capacity (TAC), oxidized LDL (oxLDL), and glutathione. Our results showed that Al intoxication reduced significantly following EDTA and Cellfood treatment, and clinical symptoms improved. After treatment, ROS, oxLDL, and homocysteine decreased significantly, whereas vitamin B12, folate and TAC improved significantly. In conclusion, our data show the efficacy of chelation therapy associated with Cellfood in subjects affected by Al intoxication who have developed ND.

  2. Preliminary in vitro evaluation of Caryocar coriaceum Wittm. leaf and bark extracts as antioxidants

    Directory of Open Access Journals (Sweden)

    Sandra Mara Duavy

    2016-07-01

    Full Text Available Summary. Caryocar coriaceum Wittm (C. coriaceum has been traditionally used as wound healing and for the treatment of inflammatory diseases. This study was carried out to evaluate in vitro antioxidant activity of the tree leaf and fruit bark extracts from C.coriaceum. The extracts exhibited a similar and significant DPPH and hydroxyl radical scavenging activity and were effective in reducing and chelating iron. Indeed, the extracts diminished lipid peroxidation ferrous-induced and reactive species overproduction calcium-induced in liver homogenate. The extracts did not modify the levels of superoxide radical in liver mitochondria treated with antimicin A. The extract samples presented significant content of total phenols. Our findings showed that the extracts from species C. coriaceum were strong antioxidants in vitro and point that they might be useful as potent sources of natural bioactive compounds for further in vivo studies. Industrial Relevance. This study demonstrated, for the first time, the in vitro antioxidant action of leaf and bark fruit extracts from species C. Coriaceum. The extracts were able to scavenge free radicals, modulate iron redox state and inhibit lipid peroxidation and reactive oxygen species (ROS overproduction. In addition to the pharmacological activities already documented toward fruit known as Pequi, the results obtained here highlight leaves and fruit barks as important antioxidant agents and sources of phenolic compounds, characteristics that potentiate the relevance of species C. Coriaceum as functional/nutraceutical food. Keywords: Caryocar coriaceum Wittm; pequi; antioxidant activity; oxidative stress

  3. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease.

    Science.gov (United States)

    House, Emily; Collingwood, Joanna; Khan, Ayesha; Korchazkina, Olga; Berthon, Guy; Exley, Christopher

    2004-06-01

    Metals are found associated with beta-pleated sheets of Abeta42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Abeta peptides. We have followed fibrillisation of Abeta42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Abeta42 either alone or in the presence of Al(III) or Fe(III) formed beta-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of beta-pleated sheets of Abeta42and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Abeta42 either alone or in the presence of added Al(III) or Fe(III) did not form beta-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent beta-pleated amyloid formation in the same treatments and promoted beta-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Abeta42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabilising the structure of beta-pleated amyloid. If the formation of such amyloid is critical to the aetiology of AD then the chelation of Al(III) and Fe(III) may prove to be a protective mechanism whilst the chelation of Cu(II) and Zn(II) without also chelating Al(III) and Fe(III) might actually exacerbate the condition.

  4. Rapid reductive degradation of aqueous p-nitrophenol using nanoscale zero-valent iron particles immobilized on mesoporous silica with enhanced antioxidation effect

    Science.gov (United States)

    Tang, Lin; Tang, Jing; Zeng, Guangming; Yang, Guide; Xie, Xia; Zhou, Yaoyu; Pang, Ya; Fang, Yan; Wang, Jiajia; Xiong, Weiping

    2015-04-01

    In this study, nanoscale zero-valent iron particles immobilized on mesoporous silica (nZVI/SBA-15) were successfully prepared for effective degradation of p-nitrophenol (PNP). The nZVI/SBA-15 composites were characterized by N2 adsorption/desorption, transmission electron microscopy (TEM), UV-vis spectrum and X-ray photoelectron spectroscopy (XPS). Results showed that abundant ultrasmall nanoscale zero-valent iron particles were formed and well dispersed on mesoporous silica (SBA-15). Batch experiments revealed that PNP removal declined from 96.70% to 16.14% as solution pH increased from 3.0 to 9.0. Besides, degradation equilibrium was reached within 5 min, which was independent of initial PNP concentration. Furthermore, only a little PNP elimination on SBA-15 indicated that nZVI immobilized on mesoporous silica was mainly responsible for the target contaminant removal. The UV-vis spectrum and XPS measurement confirmed that the PNP removal was a reductive degradation process, which was further proved by the detected intermediates using gas chromatography-mass spectrometry (GC/MS). The excellent antioxidation ability had been discovered with more than 80% of PNP being removed by nZVI/SBA-15 treated with 30 days' exposure to air. These results demonstrated the feasible and potential application of nZVI/SBA-15 composites in organic wastewater treatment.

  5. Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay

    Directory of Open Access Journals (Sweden)

    Bhaveshkumar D. Dhorajiya

    2014-01-01

    Full Text Available A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3-TBA manifested the best protective effect against DNA damage induced by bleomycin.

  6. Effect of metal chelators on the oxidative stability of model wine.

    Science.gov (United States)

    Kreitman, Gal Y; Cantu, Annegret; Waterhouse, Andrew L; Elias, Ryan J

    2013-10-02

    Oxidation is a major problem with respect to wine quality, and winemakers have few tools at their disposal to control it. In this study, the effect of exogenous Fe(II) (bipyridine; Ferrozine) and Fe(III) chelators (ethylenediaminetetraacetic acid, EDTA; phytic acid) on nonenzymatic wine oxidation was examined. The ability of these chelators to affect the formation of 1-hydroxyethyl radicals (1-HER) and acetaldehyde was measured using a spin trapping technique with electron paramagnetic resonance (EPR) and by HPLC-PDA, respectively. The chelators were then investigated for their ability to prevent the oxidative loss of an important aroma-active thiol, 3-mercaptohexan-1-ol (3MH). The Fe(II)-specific chelators were more effective than the Fe(III) chelators with respect to 1-HER inhibition during the early stages of oxidation and significantly reduced oxidation markers compared to a control during the study. However, although the addition of Fe(III) chelators was less effective or even showed an initial pro-oxidant activity, the Fe(III) chelators proved to be more effective antioxidants compared to Fe(II) chelators after 8 days of accelerated oxidation. In addition, it is shown for the first time that Fe(II) and Fe(III) chelators can significantly inhibit the oxidative loss of 3MH in model wine.

  7. Examining the fixation kinetics of chelated and non-chelated copper micronutrient and the applications to micronutrient management in semi-arid alkaline soils

    Science.gov (United States)

    Udeigwe, T. K.; Eichmann, M. B.; Menkiti, M. C.

    2015-10-01

    The relationship between the deficiency of a nutrient in plants and its total concentration in the soil is complex. This study examined and compared the fixation and fixation kinetics of copper (Cu) in chelated (Ethylene diamine tetraacetic acid, EDTA) and non-chelated mixed systems of micronutrients in the semi-arid soils of the Southern High Plains, US using findings from Cu extraction studies and kinetic models. Approximately, 22 % more Cu was fixed in the non-chelated system within the first 14 days with only 7 % difference between the two systems by day 90. Findings suggest a decrease in the effectiveness of chelated micronutrient over time, highlighting the significance of timing even when chelated micronutrients are applied. The strengths of the relationship of change in available Cu with respect to other micronutrients [iron (Fe), manganese (Mn), and zinc (Zn)] were higher in the non-chelated system (R2: 0.68-0.94), compared to the chelated (R2: 0.42-0.81) with slopes of 0.40 (Cu-Fe), 0.31 (Cu-Mn), and 1.04 (Cu-Zn) in the non-chelated system and 0.26 (Cu-Fe), 0.22 (Cu-Mn), and 0.90 (Cu-Zn) in the chelated. Reduction in the amount of available Cu was best described by the power function model (R2 = 0.91, SE = 0.081) in the non-chelated system and second order model (R2 = 0.95, SE = 0.010) in the chelated system. The applications generated from this study could be used as tools for improved micronutrient management and also provide baseline data for future work in other semi-arid/arid alkaline soils of the world. Findings are also more applicable to field settings, an improvement over related previous studies.

  8. In Vitro Ion Chelating, Antioxidative Mechanism of Extracts from Fruits and Barks of Tetrapleura tetraptera and Their Protective Effects against Fenton Mediated Toxicity of Metal Ions on Liver Homogenates

    Directory of Open Access Journals (Sweden)

    Bruno Moukette Moukette

    2015-01-01

    Full Text Available The aim of the present study was to investigate the antioxidant activity and protective potential of T. tetraptera extracts against ion toxicity. The antioxidant activity of the extracts was investigated spectrophotometrically against several radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH•, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS•, hydroxyl radical (HO•, and nitric oxide (NO•, followed by the ferric reducing power, total phenols, flavonoid, and flavonol contents. The effects of the extracts on catalase (CAT, superoxide dismutase (SOD, and peroxidase activities were also determined using the standard methods as well as the polyphenol profile using HPLC. The results showed that the hydroethanolic extract of T. tetraptera (CFH has the lowest IC50 value with the DPPH, ABTS, OH, and NO radicals. The same extract also exhibited the significantly higher level of total phenols (37.24 ± 2.00 CAE/g dried extract; flavonoids (11.36 ± 1.88 QE/g dried extract; and flavonols contents (3.95 ± 0.39 QE/g dried extract. The HPLC profile of T. tetraptera revealed that eugenol (958.81 ± 00 mg/g DW, quercetin (353.78 ± 00 mg/g DW, and rutin (210.54 ± 00 mg/g DW were higher in the fruit than the bark extracts. In conclusion, extracts from T. tetraptera may act as a protector against oxidative mediated ion toxicity.

  9. Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

    OpenAIRE

    Adly, Amira A.M.; Dalia N. Toaima; Noha Refaat Mohamed; Karim Mahmoud Abu El Seoud

    2014-01-01

    Background: Limited data are available about renal involvement in thalassemia patients. Renal dysfunction in these patients seems to be multifactorial attributed mainly to long standing anemia, chronic hypoxia, iron overload and toxicity of iron chelators. Objective: To assess the frequency of subclinical glomerular and tubular dysfunctions in children and adolescents with β-thalassemia major and intermedia, and to correlate these findings with the degree of iron overload and type of chela...

  10. Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds

    Directory of Open Access Journals (Sweden)

    Diaz Patricia

    2012-11-01

    Full Text Available Abstract Background This study aims to determine the relationship between the antioxidant and anti-inflammatory activities of the thirteen herbs and two fungi extracts, and their total phenolic and flavonoid contents. Methods Antioxidant activities were evaluated by four assays: an antioxidant activity assay using Saccharomyces cerevisiae, a DPPH ((2, 2-diphenyl-1-picrylhydrazyl assay to assess free radical scavenging, an assay assessing ferrous ions or iron (II chelating ability, and a ferric reducing antioxidant power (FRAP assay. Total phenolic and flavonoid contents were determined using the Folin-Ciocalteu and aluminium chloride methods, respectively. Anti-inflammatory activities were determined by measuring the inhibition of nitric oxide and TNF-α production in lipopolysaccharide- and interferon-γ-activated J774A.1 macrophages. Their cytotoxicities against macrophages were determined by MTT assay. Results A positive linear correlation between antioxidant activities and the total phenolic and flavonoid content of the plant extracts was found. The plant extracts with high phenolic and flavonoid content also exhibited significant anti-inflammatory activity with good cell viability. Conclusion The selected herbs could be a rich source of antioxidants and free radical scavenging compounds. The levels of phenolic and flavonoid compounds were correlated with the antioxidant and anti-inflammatory activities of the extracts from the herbs.

  11. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron.

    Science.gov (United States)

    van der Ende, A; du Maine, A; Simmons, C F; Schwartz, A L; Strous, G J

    1987-06-25

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at least each 19 min. The accumulated iron is released from the BeWo cells at a considerable rate. The time required to release 50% of previously accumulated iron into the extracellular medium is 30 h. This release process is cell line-specific as HeLa cells release very little if any iron. The release of iron by BeWo cells is stimulated by exogenous chelators such as apotransferrin, diethylenetriaminepenta-acetic acid, desferral, and apolactoferrin. The time required to release 50% of the previously accumulated iron into medium supplemented with chelator is 15 h. In the absence of added chelators iron is released as a low molecular weight complex, whereas in the presence of chelator the iron is found complexed to the chelator. Uptake of iron is inhibited by 250 microM primaquine or 2.5 microM monensin. However, the release of iron is not inhibited by these drugs. Intracellular iron is stored bound to ferritin. A model for the release of iron by BeWo cells and its implication for transplacental iron transport is discussed.

  12. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    Science.gov (United States)

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-05

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  13. Extraction optimization of polysaccharide from Zanthoxylum bungeanum using RSM and its antioxidant activity.

    Science.gov (United States)

    Li, Peiqin; Zhou, Ligang; Mou, Yan; Mao, Ziling

    2015-01-01

    Polysaccharide prepared from pericarp of Zanthoxylum bungeanum was proved to possess excellent antioxidant activities in vitro by using reducing ferric iron power, DPPH radical scavenging activity, chelating ferrous iron capacity, and hydroxyl radical scavenging activity assays in the present study. In those four antioxidant assay models, Z. bungeanum polysaccharide (ZBP) displayed prominent antioxidant activities with low EC50 values of 0.011, 0.021, 0.056 and 0.008 mg/mL, respectively. Moreover, the extraction process of ZBP was further optimized by response surface methodology combined with Box-Behnken design. The highest polysaccharide yield 13.96%, which agreed closely with the predicted yield 13.20%, was obtained under the optimal extraction conditions as follows: extraction temperature 89 °C, extraction time 3h, ratio of water volume (mL) to raw material weight (g) 29 (v/w), and extraction number two times. The present research not only provide theoretical basis for exploitation of natural polysaccharide antioxidants, but also establish the foundation of large-scale production and further system utilization of ZBP.

  14. In vitro evaluation of antioxidant and cytotoxic activities of lignin fractions extracted from Acacia nilotica.

    Science.gov (United States)

    Barapatre, Anand; Meena, Avtar Singh; Mekala, Sowmya; Das, Amitava; Jha, Harit

    2016-05-01

    Lignin is one of the most important phytomacromolecule with diverse therapeutic properties such as anticancer, antimicrobial, anti-inflammatory and immune-stimulatory. The present study was carried out to evaluate the in vitro antioxidant, free radical scavenging and anti-proliferative/cytotoxic activities of eleven different lignin fractions, extracted from the wood of Acacia nilotica by pressurized solvent extraction (PSE) and successive solvent extraction (SSE) methods. Results indicate that the PSE fractions have high polyphenolic content and reducing power. However, the antioxidant efficiency examined by DPPH and ABTS radical scavenging assay was higher in SSE fractions. All lignin fractions revealed a significant ability to scavenge nitric oxide, hydroxyl and superoxide radicals. The extracted lignin fractions display high ferric ion reducing capacity and also possess excellent antioxidant potential in the hydrophobic (linoleic acid) system. Fractions extracted by polar solvent has the highest iron (Fe(2+)) chelating activity as compared to other factions, indicating their effect on the redox cycling of iron. Four lignin fractions depicted higher cytotoxic potential (IC50: 2-15 μg/mL) towards breast cancer cell line (MCF-7) but were ineffective (IC50: ≥ 100 μg/mL) against normal primary human hepatic stellate cells (HHSteCs). These findings suggest that the lignin extracts of A. nilotica wood has a remarkable potential to prevent disease caused by the overproduction of radicals and also seem to be a promising candidate as natural antioxidant and anti-cancer agents.

  15. Antioxidant activity of leaves and inflorescence of Eryngium Caucasicum Trautv at flowering stage

    Directory of Open Access Journals (Sweden)

    Mohamamd Ali Ebrahimzadeh

    2009-01-01

    Full Text Available Methanol extracts of leaves and inflorescence of Eryngium Caucasicum Trautv at flowering stage were investigated for their antioxidant activities employing six in vitro assay systems, i.e. DPPH and nitric oxide radical scavenging, reducing power, linoleic acid and iron ion chelating power. IC50 for DPPH radical-scavenging activity was 0.15 ± 0.01 for leaves and 0.39 ± 0.02 mg ml−1 for inflorescence. Reducing powers of both extracts increased with the increase of their concentrations. Leaves extract showed better activity than Vitamin C (p< 0.05. Extracts showed weak nitric oxide-scavenging activity. Leaves extract exhibited better Fe2+ chelating ability (IC50=0.25 mg ml−1 that was comparable with EDTA. (IC50=18 ìg ml−1. Inflorescence extracts had shown a very weak activity. Extracts showed very good scavenging activity of H2O2. IC50 was 25.5 ± 1.3 for leaves and 177.2 ± 11.6 mg ml−1 for inflorescence, respectively. No antioxidant activity exhibited in linoleic acid test. Extracts exhibited different levels of antioxidant activity in all the models studied.

  16. Betalain, Acid Ascorbic, Phenolic Contents and Antioxidant Properties of Purple, Red, Yellow and White Cactus Pears

    Science.gov (United States)

    Sumaya-Martínez, María Teresa; Cruz-Jaime, Sandra; Madrigal-Santillán, Eduardo; García-Paredes, Juan Diego; Cariño-Cortés, Raquel; Cruz-Cansino, Nelly; Valadez-Vega, Carmen; Martinez-Cardenas, Leonardo; Alanís-García, Ernesto

    2011-01-01

    Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a β-carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH•), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05) and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05) to the concentration of total phenolic compounds (R2 = 0.90) and ascorbic acid (R2 = 0.86). All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•. PMID:22072899

  17. Betalain, Acid Ascorbic, Phenolic Contents and Antioxidant Properties of Purple, Red, Yellow and White Cactus Pears

    Directory of Open Access Journals (Sweden)

    Leonardo Martinez-Cardenas

    2011-09-01

    Full Text Available Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a β-carotene-linoleic acid emulsion, and iron (II chelation, the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II-dependent hydroxyl radicals (OH•, in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05 and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05 to the concentration of total phenolic compounds (R2 = 0.90 and ascorbic acid (R2 = 0.86. All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•.

  18. Betalain, Acid ascorbic, phenolic contents and antioxidant properties of purple, red, yellow and white cactus pears.

    Science.gov (United States)

    Sumaya-Martínez, María Teresa; Cruz-Jaime, Sandra; Madrigal-Santillán, Eduardo; García-Paredes, Juan Diego; Cariño-Cortés, Raquel; Cruz-Cansino, Nelly; Valadez-Vega, Carmen; Martinez-Cardenas, Leonardo; Alanís-García, Ernesto

    2011-01-01

    Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a β-carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH•), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•.

  19. Stress hardening under long-term cadmium treatment is correlated with the activation of antioxidative defence and iron acquisition of chloroplasts in Populus.

    Science.gov (United States)

    Solti, Ádám; Sárvári, Éva; Szöllősi, Erzsébet; Tóth, Brigitta; Mészáros, Ilona; Fodor, Ferenc; Szigeti, Zoltán

    2016-09-01

    Cadmium (Cd), a highly toxic heavy metal affects growth and metabolic pathways in plants, including photosynthesis. Though Cd is a transition metal with no redox capacity, it generates reactive oxygen species (ROS) indirectly and causes oxidative stress. Nevertheless, the mechanisms involved in long-term Cd tolerance of poplar, candidate for Cd phytoremediation, are not well known. Hydroponically cultured poplar (Populus jacquemontiana var. glauca cv. 'Kopeczkii') plants were treated with 10 μM Cd for 4 weeks. Following a period of functional decline, the plants performed acclimation to the Cd induced oxidative stress as indicated by the decreased leaf malondialdehyde (MDA) content and the recovery of most photosynthetic parameters. The increased activity of peroxidases (PODs) could have a great impact on the elimination of hydrogen peroxide, and thus the recovery of photosynthesis, while the function of superoxide dismutase (SOD) isoforms seemed to be less important. Re-distribution of the iron content of leaf mesophyll cells into the chloroplasts contributed to the biosynthesis of the photosynthetic apparatus and some antioxidative enzymes. The delayed increase in photosynthetic activity in relation to the decline in the level of lipid peroxidation indicates that elimination of oxidative stress damage by acclimation mechanisms is required for the restoration of the photosynthetic apparatus during long-term Cd treatment.

  20. Fortification Iron as Ferrous Sulfate Plus Ascorbic Acid Is More Rapidly Absorbed Than as Sodium Iron EDTA but Neither Increases Serum Nontransferrin-Bound Iron in Women

    NARCIS (Netherlands)

    Troesch, B.; Egli, I.; Zeder, C.; Hurrell, R.F.; Zimmermann, M.B.

    2011-01-01

    The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished wi

  1. Synergistic effect of chelators and Herbaspirillum sp. GW103 on lead phytoextraction and its induced oxidative stress in Zea mays.

    Science.gov (United States)

    Govarthanan, Muthusamy; Kamala-Kannan, Seralathan; Kim, Seol Ah; Seo, Young-Seok; Park, Jung-Hee; Oh, Byung-Taek

    2016-10-01

    Phytoremediation is an in situ, low-cost strategy for cleanup of the sites contaminated with heavy metals. Experiments were conducted to assess the impact of synthetic chelators and plant growth-promoting rhizosphere bacteria (Herbaspirillum sp. GW103) on heavy metal lead (Pb) uptake in Z. mays cultivated in Pb-contaminated soil. The present study investigated the Pb phytoaccumulation rate and plant antioxidant enzyme activities in Z. mays exposed to 100 mg/kg of PbNO3. The combination of gluconic acid (GA) with Herbaspirillum sp. GW103 treatment showed higher Pb solubility (18.9 mg/kg) compared with other chelators. The chemical chelators showed the significant difference in phytoaccumulation as well as antioxidant enzyme activities. The antioxidant enzymes such as catalase, peroxidase and superoxide dismutase activities changed under Pb stress. The study indicated that increased activity of antioxidant enzymes may play as signal inducers to fight against Pb.

  2. In vitro antioxidant and anti-inflammatory properties of Limonium algarvense flowers' infusions and decoctions: A comparison with green tea (Camellia sinensis).

    Science.gov (United States)

    Rodrigues, Maria João; Neves, Vanessa; Martins, Alice; Rauter, Amélia P; Neng, Nuno R; Nogueira, José M F; Varela, João; Barreira, Luísa; Custódio, Luísa

    2016-06-01

    This work reports the in vitro antioxidant and anti-inflammatory activities and toxicity of infusions and decoctions of Limonium algarvense flowers, and green tea. The total contents in different phenolic groups and the quantification of individual phenolics by HPLC are also reported. L. algarvense and green tea had similar antioxidant properties, except for hydroxyl radical-scavenging activity, higher on green tea, and iron chelating potential, higher on L. algarvense. The later species also had the uppermost anti-inflammatory potential. Green tea decoction had the highest content of phenolic groups, but the infusion of L. algarvense had higher amounts of salicylic, gallic and coumaric acids. L. algarvense was not toxic, whereas green tea was toxic for S17 cells. Under our experimental conditions, infusions and decoctions of L. algarvense flowers had similar or higher antioxidant and anti-inflammatory properties than green tea, and thus, may be useful for alleviating symptoms associated with oxidative and inflammatory-related diseases.

  3. Emulsifier type, metal chelation and pH affect oxidative stability of n-3-enriched emulsions

    DEFF Research Database (Denmark)

    Haahr, Anne-Mette; Jacobsen, Charlotte

    2008-01-01

    Recent research has shown that the oxidative stability of oil-in-water emulsions is affected by the type of surfactant used as emulsifier. The aim of this study was to evaluate the effect of real food emulsifiers as well as metal chelation by EDTA and pH on the oxidative stability of a 10% n-3...... to their ability to chelate iron, scavenge free radicals, interfere with interactions between the lipid hydroperoxides and iron as well as to form a physical harrier around the oil droplets....

  4. Complexation of Flavonoids with Iron: Structure and Optical Signatures

    Science.gov (United States)

    Ren, Jun; Meng, Sheng; Lekka, Ch. E.; Kaxiras, Efthimios

    2008-03-01

    Flavonoids exhibit antioxidant behavior believed to be related to their metal ion chelation ability. We investigate the complexation mechanism of several flavonoids, quercetin, luteolin, galangin, kaempferol and chrysin with iron, the most abundant type of metal ions in the body, through first- principles electronic structure calculations based on Density Functional Theory (DFT). We find that the most likely chelation site for Fe is the 3-hydroxyl-4-carbonyl group, followed by 4- carbonyl-5-hydroxyl group and the 3'-4' hydroxyl (if present) for all the flavonoid molecules studied. Three quercetin molecules are required to saturate the bonds of a single Fe ion by forming six orthogonal Fe-O bonds, though the binding energy per molecule is highest for complexes consisting of two quercetin molecules and one Fe atom, in agreement with experiment. Optical absorption spectra calculated with time- dependent DFT serve as signatures to identify various complexes. For the iron-quercetin complexes, we find a redshift of the first absorbance peak upon complexation in good agreement with experiment; this behavior is explained by the narrowing of the optical gap of quercetin due to Fe(d)--O(p) orbital hybridization.

  5. The scientific basis for chelation: animal studies and lead chelation.

    Science.gov (United States)

    Smith, Donald; Strupp, Barbara J

    2013-12-01

    This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating

  6. Removal of cadmium from fish sauce using chelate resin.

    Science.gov (United States)

    Sasaki, Tetsuya; Araki, Ryohei; Michihata, Toshihide; Kozawa, Miyuki; Tokuda, Koji; Koyanagi, Takashi; Enomoto, Toshiki

    2015-04-15

    Fish sauce that is prepared from squid organs contains cadmium (Cd), which may be present at hazardous concentrations. Cd molecules are predominantly protein bound in freshly manufactured fish sauce, but are present in a liberated form in air-exposed fish sauce. In the present study, we developed a new method for removing both Cd forms from fish sauce using chelate resin and a previously reported tannin treatment. Sixteen-fold decreases in Cd concentrations were observed (0.78-0.05 mg/100 mL) following the removal of liberated Cd using chelate resin treatment, and the removal of protein-bound Cd using tannin treatment. Major nutritional components of fish sauce were maintained, including free amino acids and peptides, and angiotensin I-converting enzyme inhibitory and antioxidant activities.

  7. Simulated Gastrointestinal pH Condition Improves Antioxidant Properties of Wheat and Rice Flours

    Directory of Open Access Journals (Sweden)

    Nicholas M. H. Khong

    2012-06-01

    Full Text Available The present study was conducted to evaluate the antioxidant properties of wheat and rice flours under simulated gastrointestinal pH condition. After subjecting the wheat and rice flour slurries to simulated gastrointestinal pH condition, both slurries were centrifuged to obtain the crude phenolic extracts for further analyses. Extraction yield, total contents of phenolic and flavonoids were determined as such (untreated and under simulated gastrointestinal pH condition (treated. 1,1-diphenyl-2-picrylhydrazyl radical (DPPH scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid radical cation (ABTS•+ scavenging activity, ferric reducing antioxidant power (FRAP, beta-carotene bleaching (BCB and iron chelating activity assays were employed for the determination of antioxidant activity of the tested samples. In almost all of the assays performed, significant improvements in antioxidant properties (p < 0.05 were observed in both flours after treatment, suggesting that wheat and rice flours contain considerably heavy amounts of bound phenolics, and that their antioxidant properties might be improved under gastrointestinal digestive conditions.

  8. Intestinal Iron Homeostasis and Colon Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yatrik M. Shah

    2013-06-01

    Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

  9. The effect of metal chelators on the production of hydroxyl radicals in thylakoids.

    Science.gov (United States)

    Snyrychová, Iva; Pospísil, Pavel; Naus, Jan

    2006-06-01

    The effect of metal chelators (EDTA, DTPA and Desferal) on the metal-catalyzed decomposition of hydrogen peroxide was studied using EPR spin-trapping spectroscopy. The formation of hydroxyl radicals (OH*) in both chemical (Fenton reaction) and biological (thylakoids) systems was stimulated by EDTA. DTPA promoted the generation of OH* in the presence of strong reducing agents, whereas in their absence it acted as an antioxidant. Desferal suppressed OH* production even in the presence of reductants. In our study, we have shown that metal chelators can both stimulate and suppress the formation of OH*, depending on the experimental conditions. In illuminated thylakoids we have observed prooxidant effect of EDTA and DTPA, possibly due to their reduction by some component of the electron transport chain. According to our results, metal chelators should not be used as antioxidants without prior testing of their effect in given samples.

  10. Mineral components and anti-oxidant activities of tropical seaweeds

    Science.gov (United States)

    Takeshi, Suzuki; Yumiko, Yoshie-Stark; Joko, Santoso

    2005-07-01

    Seaweeds are known to hold substances of high nutritional value; they are the richest resources of minerals important to the biochemical reactions in the human body. Seaweeds also hold non-nutrient compounds like dietary fiber and polyphenols. However, there is not enough information on the mineral compounds of tropical seaweeds. Also we are interested in the antioxidant activities of seaweeds, especially those in the tropical area. In this study, Indonesian green, brown and red algae were used as experimental materials with their mineral components analyzed by using an atomic absorption spectrophotometer. The catechins and flavonoids of these seaweeds were extracted with methanol and analyzed by high performance liquid chromatography (HPLC); the antioxidant activities of these seaweeds were evaluated in a fish oil emulsion system. The mineral components of tropical seaweeds are dominated by calcium, potassium and sodium, as well as small amounts of copper, iron and zinc. A green alga usually contains epigallocatechin, gallocatechin, epigallocatechin gallate and catechin. However, catechin and its isomers are not found in some green and red algae. In the presence of a ferrous ion catalyst, all the methanol extracts from the seaweeds show significantly lower peroxide values of the emulsion than the control, and that of a green alga shows the strongest antioxidant activity. The highest chelation on ferrous ions is also found in the extract of this alga, which is significantly different from the other methanol extracts in both 3 and 24 h incubations.

  11. Mineral Components and Anti-oxidant Activities of Tropical Seaweeds

    Institute of Scientific and Technical Information of China (English)

    Suzuki Takeshi; Yoshie-Stark Yumiko; Santoso Joko

    2005-01-01

    Seaweeds are known to hold substances of high nutritional value; they are the richest resources of minerals important to the biochemical reactions in the human body. Seaweeds also hold non-nutrient compounds like dietary fiber and polyphenols. However, there is not enough information on the mineral compounds of tropical seaweeds. Also we are interested in the antioxidant activities of seaweeds, especially those in the tropical area. In this study, Indonesian green, brown and red algae were used as experimental materials with their mineral components analyzed by using an atomic absorption spectrophotometer. The catechins and flavonoids of these seaweeds were extracted with methanol and analyzed by high performance liquid chromatography (HPLC); the anti-oxidant activities of these seaweeds were evaluated in a fish oil emulsion system. The mineral components of tropical seaweeds are dominated by calcium, potassium and sodium, as well as small amounts of copper, iron and zinc. A green alga usually contains epigallocatechin, gallocatechin, epigallocatechin gallate and catechin. However, catechin and its isomers are not found in some green and red algae. In the presence of a ferrous ion catalyst, all the methanol extracts from the seaweeds show significantly lower peroxide values of the emulsion than the control,and that of a green alga shows the strongest anti-oxidant activity. The highest chelation on ferrous ions is also found in the extract of this alga, which is significantly different from the other methanol extracts in both 3 and 24 h incubations.

  12. The antioxidant and anti-cadmium toxicity properties of garlic extracts.

    Science.gov (United States)

    Boonpeng, Suwannaporn; Siripongvutikorn, Sunisa; Sae-Wong, Chutha; Sutthirak, Pornpong

    2014-11-01

    Cadmium (Cd) contamination is a highly dangerous international problem because it can transfer into the food chain and become bioaccumulated, endangering human health. Cd detoxication is very interesting particularly the method providing no undesirable side effects. Cd also causes lipid oxidation that leads to undesired food quality. Garlic (Allium sativum L.) has been used as conventional food and in herbal therapy and folklore medicine as an antibacterial, antitumorogenic, and antioxidant agent for over 5000 years. In the present work, fresh garlic and pickled garlic extracted with distilled water was brought to determine antioxidant activities in terms of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging assay, ferric reducing ability power (FRAP) assay, chelating activities, superoxide, and hydroxyl scavenging assay. The data showed that pickled garlic extracts significantly possessed more DPPH, ABTS, FRAP, superoxide, and hydroxyl scavenging assays as 11.86, 13.74, 4.9, 46.67, and 15.33 g trolox equivalent/g sample, respectively, compared with fresh one as 7.44, 7.62, 0.01, 4.07, and 8.09 g trolox equivalent/g sample, respectively. However, iron chelating activity of fresh garlic extract was higher than that of pickled garlic while there was no significant difference in the copper chelating activity of both extracts. For anti-Cd properties, pickled garlic was more effective than fresh garlic and contained less toxicity than standard diallyl disulfide (DADS). Therefore, therapeutic properties of pickled garlic favored its consumption compared with fresh and standard DADS for its antioxidant and anti-Cd properties.

  13. Antioxidant Activities of Aqueous Extract from Cultivated Fruit-bodies of Cordyceps militaris (L.) Link In Vitro

    Institute of Scientific and Technical Information of China (English)

    Yu Zhan; Cai-Hong Dong; Yi-Jian Yao

    2006-01-01

    Biological antioxidants extracted from plants and fungi have potential abilities to scavenge free radicals and inhibit lipid peroxidation, playing important roles in preventing diseases, for example, cancer, and aging induced by reactive oxygen species, which may cause oxidative damage to DNA, proteins and other macromolecules. The antioxidant potency of cultivated fruit-bodies of Cordyceps militaris (L.) Link was investigated in this study. Five established in vitro systems were employed, including the 1,1-diphenyl-2-picryldrazyl (DPPH) free radical scavenging, hydroxyl radical eliminating, iron chelating, inhibition of linoleic acid lipid peroxidation and reducing power. The aqueous extract from cultivated fruit-bodies was subjected to the test of amino acid, polysaccharide and mannitol. Ascorbic acid (Vc), butylated hydroxytoluene (BHT)and ethylenediaminetetraacetic acid (EDTA) were used as positive controls for comparisons. Among the assays, the aqueous extract of C. militaris fruit-bodies shows a significant scavenging effect on DPPH,eliminating the capability on hydroxyl radicals and the chelating effect on ferrous iron. The extract also shows positive results of inhibiting linoleic acid lipid peroxidation and reducing power.

  14. Design and Synthesis of Some New 1,3,4-Thiadiazines with Coumarin Moieties and Their Antioxidative and Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Milan Čačić

    2014-01-01

    Full Text Available A series of newly disubstituted (compounds 4a,b and trisubstituted 1,3,4-thiadiazines 5a–l with various substituents was prepared utilizing different thiosemicarbazides and 3-α-bromoacetylcoumarins as starting compounds. The structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed utilizing the corresponding analytical and spectroscopic data. All of the new thiadiazine derivatives were tested for their antioxidant activity, employing different antioxidant assays (DPPH scavenging activity, iron chelating activity, power reducing activity. Compounds 5b, 5f, 5j and 4b were proven to be the best DPPH radical scavengers, while compounds 5h and 5j have shown the best iron chelating activity. Thiadiazine derivatives were also tested on their antifungal activity against four mycotoxicogenic fungi, Aspergillus flavus, A. ochraceus, Fusarium graminearum and F. verticillioides. The best antifungal against A. flavus was proven to be compound 5e, while compounds 4a and 5c were the best antifungals on A. ochraceus, and compound 5g showed the best antifungal activity on F. verticillioides.

  15. Iron acquisition and regulation systems in Streptococcus species.

    Science.gov (United States)

    Ge, Ruiguang; Sun, Xuesong

    2014-05-01

    Gram-positive Streptococcus species are responsible for millions of cases of meningitis, bacterial pneumonia, endocarditis, erysipelas and necrotizing fasciitis. Iron is essential for the growth and survival of Streptococcus in the host environment. Streptococcus species have developed various mechanisms to uptake iron from an environment with limited available iron. Streptococcus can directly extract iron from host iron-containing proteins such as ferritin, transferrin, lactoferrin and hemoproteins, or indirectly by relying on the employment of specialized secreted hemophores (heme chelators) and small siderophore molecules (high affinity ferric chelators). This review presents the most recent discoveries in the iron acquisition system of Streptococcus species - the transporters as well as the regulators.

  16. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease.

    Science.gov (United States)

    Liu, Gang; Men, Ping; Kudo, Wataru; Perry, George; Smith, Mark A

    2009-05-22

    Oxidative stress and amyloid-beta are considered major etiological and pathological factors in the initiation and promotion of neurodegeneration in Alzheimer disease (AD). Insomuch as causes of such oxidative stress, transition metals, such as iron and copper, which are found in high concentrations in the brains of AD patients and accumulate specifically in the pathological lesions, are viewed as key contributors to the altered redox state. Likewise, the aggregation and toxicity of amyloid-beta is dependent upon transition metals. As such, chelating agents that selectively bind to and remove and/or "redox silence" transition metals have long been considered as attractive therapies for AD. However, the blood-brain barrier and neurotoxicity of many traditional metal chelators has limited their utility in AD or other neurodegenerative disorders. To circumvent this, we previously suggested that nanoparticles conjugated to iron chelators may have the potential to deliver chelators into the brain and overcome such issues as chelator bioavailability and toxic side-effects. In this study, we synthesized a prototype nanoparticle-chelator conjugate (Nano-N2PY) and demonstrated its ability to protect human cortical neurons from amyloid-beta-associated oxidative toxicity. Furthermore, Nano-N2PY nanoparticle-chelator conjugates effectively inhibited amyloid-beta aggregate formation. Overall, this study indicates that Nano-N2PY, or other nanoparticles conjugated to metal chelators, may provide a novel therapeutic strategy for AD and other neurodegenerative diseases associated with excess transition metals.

  17. First report of the nutritional profile and antioxidant potential of Holothuria arguinensis, a new resource for aquaculture in Europe.

    Science.gov (United States)

    Roggatz, Christina C; González-Wangüemert, Mercedes; Pereira, Hugo; Rodrigues, Maria João; da Silva, Manuela Moreira; Barreira, Luísa; Varela, João; Custódio, Luísa

    2016-09-01

    This work reports for the first time the nutritional profile and antioxidant potential of the edible sea cucumber Holothuria arguinensis from the North-eastern Atlantic. H. arguinensis has high levels of protein, with the amino acids profile dominated by alanine, glycine and proline and low lysine/arginine ratios. Its carbohydrate and energetic contents are also low as well as the total lipid levels, although its lipid profile is rich in polyunsaturated fatty acids (PUFA), especially arachidonic, eicosapentaenoic and docosahexaenoic acids. In addition, H. arguinensis has high levels of calcium. The water and ethanol extracts show ability to scavenge free radicals and to chelate copper and iron ions. Our results indicate that H. arguinensis has a balanced nutritional quality suitable for human consumption. In addition, it contains compounds with antioxidant potential; thus its intake can contribute for a healthy and well-balanced diet.

  18. Fermentation temperature affects the antioxidant activity of the enzyme-ripened sufu, an oriental traditional fermented product of soybean.

    Science.gov (United States)

    Huang, Yung-Hsin; Lai, Ying-Jang; Chou, Cheng-Chun

    2011-07-01

    In this study, sufu, a Chinese traditional fermented product of soybean, was prepared by ripening salted tofu cubes in the mash of Aspergillus oryzae-fermented rice-soybean koji possessing various hydrolytic enzymes at 25°C, 37°C and 45°C. Antioxidant activity including 2,2-diphenyl-2-picylhydoxyl (DPPH) radical-scavenging activity, Fe(2+)-chelating ability and reducing power exerted by the methanol extract of sufu was determined and compared with that of the non-fermented tofu extract. It was found that antioxidant activity of the sufu extracts was, generally, higher than the non-fermented tofu extract. Ripening temperature and the duration of ripening period affected the antioxidant activity of the sufu extracts. Taking into account of extraction yields, the sufu product ripened at 45°C for 16 days showed the most profound enhancement in the DPPH radical-scavenging effect and Fe(2+)-iron-chelating ability, which is 3.4 and 11.5 folds, respectively, that noted with the non-fermented tofu.

  19. Selective separation of indium by iminodiacetic acid chelating resin

    Directory of Open Access Journals (Sweden)

    M. C. B. Fortes

    2007-06-01

    Full Text Available Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite®IRC748 (Rohm and Haas Co.-USA. High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite®IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5mol/dm³ sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite®IRC748.

  20. Selective separation of indium by iminodiacetic acid chelating resin

    Energy Technology Data Exchange (ETDEWEB)

    Fortes, M.C.B.; Benedetto, J.S. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Martins, A.H. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Metalurgica e de Materiais]. E-mail: ahmartin@demet.ufmg.br

    2007-04-15

    - Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite{sup R} IRC748 (Rohm and Haas Co.-USA). High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite{sup R} IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5 mol/dm{sup 3} sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite{sup R} IRC748. (author)

  1. Investigation of in vitro cytotoxicity of the redox state of ionic iron in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Ajay Vikram Singh

    2012-01-01

    Full Text Available Background: there is an intimate relation between transition metals and cell homeostasis due to the physiological necessity of metals in vivo. Particularly, iron (ferrous and ferric state is utilized in many physiological processes of the cell but in excess has been linked with negative role contributing in many neurodegenerative processes. Objective: the aim of this study was to investigate which oxidation state of ionic iron (Ferrous (II versus Ferric (III is more toxic to neuronal cells (SHSY5Y. Materials and Methods: The neuroblastoma (SHSY5Y cells were exposed to varying concentration of ferric and ferrous iron. Morphological studies using immunofluorescence staining and microscopic analysis as confirmed by intracellular glutathione (GSH test demonstrated oxidative stress to cells in iron microenvironment. In addition, MTT assay was performed to evaluate the viability and metabolic state of the cells. Results: the results showed that ferrous form has significantly higher toxicity compared to the ferric ionic state of higher concentration. In addition, microscopic analysis shows cell fenestration at higher concentrations and swelling at intermediate ferric dosages as demonstrated by atomic force microscopy (AFM. Interestingly, the addition of a differentiation inducing factor, trans-retinoic rcid (RA retains significant viability and morphological features of the cells irrespective of the ionic state of the iron. AFM images revealed clustered aggregates arising from iron chelation with RA. Conclusions: the results indicate that Fe (II has more toxic effects on cells. In addition, it could be an interesting finding with respect to the antioxidant properties of RA as a chelating agent for the neurodegenerative therapeutics.

  2. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Science.gov (United States)

    Huang, Saibo; Lin, Huimin; Deng, Shang-gui

    2015-01-01

    The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH) were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH) were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE), longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone. PMID:26633476

  3. Study of Anti-Fatigue Effect in Rats of Ferrous Chelates Including Hairtail Protein Hydrolysates

    Directory of Open Access Journals (Sweden)

    Saibo Huang

    2015-12-01

    Full Text Available The ability of ferrous chelates including hairtail protein hydrolysates to prevent and reduce fatigue was studied in rats. After hydrolysis of hairtail surimi with papain, the hairtail protein hydrolysates (HPH were separated into three groups by range of relative molecular weight using ultrafiltration membrane separation. Hairtail proteins were then chelated with ferrous ions, and the antioxidant activity, the amino acid composition and chelation rate of the three kinds of ferrous chelates including hairtail protein hydrolysates (Fe-HPH were determined. Among the three groups, the Fe-HPH chelate showing the best conditions was selected for the anti-fatigue animal experiment. For it, experimental rats were randomly divided into seven groups. Group A was designated as the negative control group given distilled water. Group B, the positive control group, was given glutathione. Groups C, D and E were designated as the Fe-HPH chelate treatment groups and given low, medium, and high doses, respectively. Group F was designated as HPH hydrolysate treatment group, and Group G was designated as FeCl2 treatment group. The different diets were orally administered to rats for 20 days. After that time, rats were subjected to forced swimming training after 1 h of gavage. Rats given Fe-FPH chelate had higher haemoglobin regeneration efficiency (HRE, longer exhaustive swimming time and higher SOD activity. Additionally, Fe-FPH chelate was found to significantly decrease the malondialdehyde content, visibly enhance the GSH-Px activity in liver and reduce blood lactic acid of rats. Fe-HPH chelate revealed an anti-fatigue effect, similar to or better than the positive control substance and superior to HPH or Fe when provided alone.

  4. Luminescent lanthanide chelates and methods of use

    Science.gov (United States)

    Selvin, Paul R.; Hearst, John

    1997-01-01

    The invention provides lanthanide chelates capable of intense luminescence. The celates comprise a lanthanide chelator covalently joined to a coumarin-like or quinolone-like sensitizer. Exemplary sensitzers include 2- or 4-quinolones, 2- or 4-coumarins, or derivatives thereof e.g. carbostyril 124 (7-amino-4-methyl-2-quinolone), coumarin 120 (7-amino-4-methyl-2-coumarin), coumarin 124 (7-amino-4-(trifluoromethyl)-2-coumarin), aminomethyltrimethylpsoralen, etc. The chelates form high affinity complexes with lanthanides, such as terbium or europium, through chelator groups, such as DTPA. The chelates may be coupled to a wide variety of compounds to create specific labels, probes, diagnostic and/or therapeutic reagents, etc. The chelates find particular use in resonance energy transfer between chelate-lanthanide complexes and another luminescent agent, often a fluorescent non-metal based resonance energy acceptor. The methods provide useful information about the structure, conformation, relative location and/or interactions of macromolecules.

  5. Chelators for investigating zinc metalloneurochemistry.

    Science.gov (United States)

    Radford, Robert J; Lippard, Stephen J

    2013-04-01

    The physiology and pathology of mobile zinc signaling has become an important topic in metalloneurochemistry. To study the action of mobile zinc effectively, specialized tools are required that probe the temporal and positional changes of zinc ions within live tissue and cells. In the present article we describe the design and implementation of selective zinc chelators as antagonists to interrogate the function of mobile zinc, with an emphasis on the pools of vesicular zinc in the terminals of hippocampal mossy fiber buttons.

  6. Essential trace metal excretion from rats with lead exposure and during chelation therapy.

    Science.gov (United States)

    Victery, W; Miller, C R; Goyer, R A

    1986-02-01

    Urinary excretion of lead, zinc, calcium, magnesium, iron, copper, sodium, and potassium was measured in rats daily for 1 week after a 6-week exposure to 10,000 micrograms/ml lead in drinking water. Beginning on the third day, half of the lead-exposed and control rats were injected intraperitoneally with calcium disodium ethylenediaminetetraacetate (EDTA) daily for 3 days. Whole blood, plasma, and kidney metal concentrations were determined from samples obtained at the end of the experiment. Exposure to lead increased urinary excretion, not only of lead, but also of calcium, magnesium, zinc, copper, and iron. Excretion of sodium and potassium was not altered. Chelation therapy further increased excretion of lead, zinc, copper, and iron, but not magnesium. The increase in calcium excretion during chelation treatment (beyond that resulting from lead exposure per se) was accounted for by the Ca content of CaNa2-EDTA. EDTA treatment increased renal concentration of zinc but lowered renal concentration of lead, copper, and iron. These multimetal alterations may have implications for essential metal supplementation, particularly zinc, in persons being given chelation agents for excess lead exposure and in infants and children with low-level lead exposure not necessarily requiring chelation therapy.

  7. Effect of chelating agent on oxidation rate of aniline in ferrous ion activated persulfate system at neutral pH

    Institute of Scientific and Technical Information of China (English)

    张永清; 谢晓芳; 黄少斌; 梁海云

    2014-01-01

    In the interest of accelerating aniline degradation, Fe2+and chelated Fe2+activated persulfate oxidations were investigated in neutral pH condition. Three kinds of chelating agents were selected including citric acid, oxalic acid and ethylenediamine tetraaceatate (EDTA) to maintain available Fe2+. The results indicate that the concentration of chelating agent and ferrous ion didn’t follow a linear relationship with the degradation rate of aniline. A 1/1 ratio of chelating agent/Fe2+results in a higher degradation rate compared to the results by other ratios. The oxidation enhancement factor using oxalic acid was found to be relatively low. In contrast, citric acid is more suitable chelating agent in the ferrous iron activated persulfate system and aniline exhibits a highest degradation with a persulfate/Fe2+/citric acid/aniline molar ratio of 50/25/25/1 compared to other molar ratios.

  8. New rat models of iron sucrose-induced iron overload.

    Science.gov (United States)

    Vu'o'ng Lê, Bá; Khorsi-Cauet, Hafida; Villegier, Anne-Sophie; Bach, Véronique; Gay-Quéheillard, Jérôme

    2011-07-01

    The majority of murine models of iron sucrose-induced iron overload were carried out in adult subjects. This cannot reflect the high risk of iron overload in children who have an increased need for iron. In this study, we developed four experimental iron overload models in young rats using iron sucrose and evaluated different markers of iron overload, tissue oxidative stress and inflammation as its consequences. Iron overload was observed in all iron-treated rats, as evidenced by significant increases in serum iron indices, expression of liver hepcidin gene and total tissue iron content compared with control rats. We also showed that total tissue iron content was mainly associated with the dose of iron whereas serum iron indices depended essentially on the duration of iron administration. However, no differences in tissue inflammatory and antioxidant parameters from controls were observed. Furthermore, only rats exposed to daily iron injection at a dose of 75 mg/kg body weight for one week revealed a significant increase in lipid peroxidation in iron-treated rats compared with their controls. The present results suggest a correlation between iron overload levels and the dose of iron, as well as the duration and frequency of iron injection and confirm that iron sucrose may not play a crucial role in inflammation and oxidative stress. This study provides important information about iron sucrose-induced iron overload in rats and may be useful for iron sucrose therapy for iron deficiency anemia as well as for the prevention and diagnosis of iron sucrose-induced iron overload in pediatric patients.

  9. Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism.

    Directory of Open Access Journals (Sweden)

    Richard D Horniblow

    Full Text Available Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05 and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease.

  10. In vitro and in vivo evaluation of anti-arthritic, antioxidant efficacy of fucoidan from Undaria pinnatifida (Harvey) Suringar.

    Science.gov (United States)

    Phull, Abdul-Rehman; Majid, Muhammad; Haq, Ihsan-Ul; Khan, Muhammad Rashid; Kim, Song Ja

    2017-04-01

    Seaweed and their constituents have been traditionally employed for the management of various human pathologic conditions such as edema, urinary disorders and inflammatory anomalies. The current study was performed to investigate the antioxidant and anti-arthritic effects of fucoidan from Undaria pinnatifida. A noteworthy in vitro antioxidant potential at 500μg/ml in 2, 2-diphenyl-1-picrylhydrazyl scavenging assay (80% inhibition), nitrogen oxide inhibition assay (71.83%), hydroxyl scavenging assay (71.92%), iron chelating assay (73.55%) and a substantial ascorbic acid equivalent reducing power (399.35μg/mg ascorbic acid equivalent) and total antioxidant capacity (402.29μg/mg AAE) suggested fucoidan a good antioxidant agent. Down regulation of COX-2 expression in rabbit articular chondrocytes in a dose (0-100μg) and time (0-48h) dependent manner, unveiled its in vitro anti-inflammatory significance. In vivo carrageenan induced inflammatory rat model demonstrated a 68.19% inhibition of inflammation whereas an inflammation inhibition potential of 79.38% was recorded in anti-arthritic complete Freund's adjuvant-induced arthritic rat model. A substantial ameliorating effect on altered hematological and biochemical parameters in arthritic rats was also observed. Therefore, findings of the present study prospects fucoidan as a potential antioxidant that can effectively abrogate oxidative stress, edema and arthritis-mediated inflammation and mechanistic studies are recommended for observed activities.

  11. Impacto da farinha de mandioca fortificada com ferro aminoácido quelato no nível de hemoglobina de pré-escolares Impact of cassava flour fortified with iron amino acid chelate on the hemoglobin level in pre-schools

    Directory of Open Access Journals (Sweden)

    Rahilda Brito Tuma

    2003-01-01

    Full Text Available OBJETIVO: Avaliou-se o impacto da farinha de mandioca fortificada com ferro aminoácido quelato em 80 pré-escolares de uma Unidade Filantrópica de Manaus, AM, distribuídos aleatoriamente em quatro grupos de 20 crianças cada, por um período de 120 dias. MÉTODOS: Foram utilizadas farinha de mandioca sem fortificação (Grupo zero e fortificada com 1, 2 e 3mg de Fe/dia, correspondendo a quantias diárias de 5, 10 e 15g de farinha, respectivamente, as quais foram distribuídas no horário do almoço, sendo ainda entregue às famílias a quantidade destinada ao consumo do final de semana. O estado nutricional das crianças foi avaliado no início e ao final do experimento, adotando-se como limite discriminatório entre eutrofia/desnutrição o ponto de corte OBJECTIVE: The impact of the cassava flour fortified with iron amino acid chelate was evaluated in 80 pre-scholars of a Philanthropic Unit of Manaus, state of Amazonas, randomly distributed in four groups of 20 children each, for a period of 120 days. METHODS: Cassava flour was used without fortification (group zero or fortified with 1, 2 and 3mg of Fe/day, corresponding respectively to 5, 10 and 15g of flour/day, which were given to the children at lunch time on weekdays. The equivalent amount was previously distributed to their families for flour intake also during the weekends. In the beginning and at the end of the experiment the children's nutritional status was evaluated, being adopted the cutoff point <-2 Z-scores as a discriminating limit between eutrophy/malnutrition, in agreement with the World Health Organization criteria, as well as being established as a cutoff point for the occurrence of iron deficiency anemia a hemoglobin rate of less than 11g/dL. RESULTS: At the end of this study, children recovered from chronic malnutrition, and a significant increase (p <5% of the hemoglobin rates, independently of iron concentration, from 11.4±0.9g/dL to 12.2±0.8g/dL, was observed in

  12. Iron-binding properties of sugar cane yeast peptides.

    Science.gov (United States)

    de la Hoz, Lucia; Ponezi, Alexandre N; Milani, Raquel F; Nunes da Silva, Vera S; Sonia de Souza, A; Bertoldo-Pacheco, Maria Teresa

    2014-01-01

    The extract of sugar-cane yeast (Saccharomyces cerevisiae) was enzymatically hydrolysed by Alcalase, Protex or Viscozyme. Hydrolysates were fractionated using a membrane ultrafiltration system and peptides smaller than 5kDa were evaluated for iron chelating ability through measurements of iron solubility, binding capacity and dialyzability. Iron-chelating peptides were isolated using immobilized metal affinity chromatography (IMAC). They showed higher content of His, Lys, and Arg than the original hydrolysates. In spite of poor iron solubility, hydrolysates of Viscozyme provided higher iron dialyzability than those of other enzymes. This means that more chelates of iron or complexes were formed and these kept the iron stable during simulated gastro-intestinal digestion in vitro, improving its dialyzability.

  13. Sequence diversity and enzyme activity of ferric-chelate reductase LeFRO1 in tomato.

    Science.gov (United States)

    Kong, Danyu; Chen, Chunlin; Wu, Huilan; Li, Ye; Li, Junming; Ling, Hong-Qing

    2013-11-20

    Ferric-chelate reductase which functions in the reduction of ferric to ferrous iron on root surface is a critical protein for iron homeostasis in strategy I plants. LeFRO1 is a major ferric-chelate reductase involved in iron uptake in tomato. To identify the natural variations of LeFRO1 and to assess their effect on the ferric-chelate reductase activity, we cloned the coding sequences of LeFRO1 from 16 tomato varieties collected from different regions, and detected three types of LeFRO1 (LeFRO1(MM), LeFRO1(Ailsa) and LeFRO1(Monita)) with five amino acid variations at the positions 21, 24, 112, 195 and 582. Enzyme activity assay revealed that the three types of LeFRO1 possessed different ferric-chelate reductase activity (LeFRO1(Ailsa) > LeFRO1(MM) > LeFRO1(Monita)). The 112th amino acid residue Ala of LeFRO1 is critical for maintaining the high activity of ferric-chelate reductase, because modification of this amino acid resulted in a significant reduction of enzyme activity. Further, we showed that the combination of the amino acid residue Ile at the site 24 with Lys at the site 582 played a positive role in the enzyme activity of LeFRO1. In conclusion, the findings are helpful to understand the natural adaptation mechanisms of plants to iron-limiting stress, and may provide new knowledge to select and manipulate LeFRO1 for improving the iron deficiency tolerance in tomato.

  14. ELECTED PROBLEMS RELATED TO ENVIRONMENTAL HEAVY METALS EXPOSURE AND CHELATION THERAPY

    Directory of Open Access Journals (Sweden)

    Anna Skoczyńska

    2010-09-01

    Full Text Available Background: Exposure to heavy metals leads to functional and metabolic disturbances and many of them are included in pathogenesis of common diseases (arterial hypertension, atherosclerosis, neurodegenerative processes. In this context new therapeutic and prophylactic strategies are necessary. Patients diagnosed with chronic heavy metals intoxication usually require chelation to increase mobilisation of metals from tissues and elimination of them via urine. Acute poisoning with toxic metal may be difficult to diagnosis, especially in case of accidental intoxication or suicidal intention. Patients also require chelation after causative factor is identified. Objectives: To describe some problems connected with toxicity of metals poisoning and to review pharmacologic therapies that could have a role in poisoning with metals. Methods: A review of the literature was carried out and expert opinion expressed. Results/conclusion: Chelation is a common therapy in case of poisoning with toxic metals but it is satisfied only partially. A combined therapy with structurally different chelators or long-term acting chelators could become viable alternatives in the future. A combined therapy with an antioxidant plus chelator may be a good choice in patients chronically poisoned with metals. Exposure to lead should be taken into account during estimation of global cardiovascular risk.

  15. Iron and Acinetobacter baumannii Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Valentina Gentile

    2014-08-01

    Full Text Available Acinetobacter baumannii is an emerging nosocomial pathogen, responsible for infection outbreaks worldwide. The pathogenicity of this bacterium is mainly due to its multidrug-resistance and ability to form biofilm on abiotic surfaces, which facilitate long-term persistence in the hospital setting. Given the crucial role of iron in A. baumannii nutrition and pathogenicity, iron metabolism has been considered as a possible target for chelation-based antibacterial chemotherapy. In this study, we investigated the effect of iron restriction on A. baumannii growth and biofilm formation using different iron chelators and culture conditions. We report substantial inter-strain variability and growth medium-dependence for biofilm formation by A. baumannii isolates from veterinary and clinical sources. Neither planktonic nor biofilm growth of A. baumannii was affected by exogenous chelators. Biofilm formation was either stimulated by iron or not responsive to iron in the majority of isolates tested, indicating that iron starvation is not sensed as an overall biofilm-inducing stimulus by A. baumannii. The impressive iron withholding capacity of this bacterium should be taken into account for future development of chelation-based antimicrobial and anti-biofilm therapies.

  16. High-accuracy determination of iron in seawater by isotope dilution multiple collector inductively coupled plasma mass spectrometry (ID-MC-ICP-MS) using nitrilotriacetic acid chelating resin for pre-concentration and matrix separation

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Jeroen de [Universite Libre de Bruxelles (ULB), Departement des Sciences de la Terre et de l' Environnement (DSTE), Unite Isotopes: Petrologie et Environnement - IPE CP 160/02, Avenue F.D. Roosevelt 50, B-1050 Brussels (Belgium)], E-mail: jdejong@ulb.ac.be; Schoemann, Veronique [Universite Libre de Bruxelles (ULB), Ecologie des Systemes Aquatiques (ESA) CP 221, Avenue F.D. Roosevelt 50, B-1050 Brussels (Belgium); Lannuzel, Delphine [Universite Libre de Bruxelles (ULB), Departement des Sciences de la Terre et de l' Environnement (DSTE), Laboratoire d' Oceanographie Chimique et Geochimie des Eaux - LOCGE CP 208, Avenue F.D. Roosevelt 50, B-1050 Brussels (Belgium); Tison, Jean-Louis [Universite Libre de Bruxelles (ULB), Departement des Sciences de la Terre et de l' Environnement (DSTE), Laboratoire de Glaciologie - GLACIOL CP 160/03, Avenue F.D. Roosevelt 50, B-1050 Brussels (Belgium); Mattielli, Nadine [Universite Libre de Bruxelles (ULB), Departement des Sciences de la Terre et de l' Environnement (DSTE), Unite Isotopes: Petrologie et Environnement - IPE CP 160/02, Avenue F.D. Roosevelt 50, B-1050 Brussels (Belgium)

    2008-08-15

    In the present paper we describe a robust and simple method to measure dissolved iron (DFe) concentrations in seawater down to <0.1 nmol L{sup -1} level, by isotope dilution multiple collector inductively coupled plasma mass spectrometry (ID-MC-ICP-MS) using a {sup 54}Fe spike and measuring the {sup 57}Fe/{sup 54}Fe ratio. The method provides for a pre-concentration step (100:1) by micro-columns filled with the resin NTA Superflow of 50 mL seawater samples acidified to pH 1.9. NTA Superflow is demonstrated to quantitatively extract Fe from acidified seawater samples at this pH. Blanks are kept low (grand mean 0.045 {+-} 0.020 nmol L{sup -1}, n = 21, 3x S.D. limit of detection per session 0.020-0.069 nmol L{sup -1} range), as no buffer is required to adjust the sample pH for optimal extraction, and no other reagents are needed than ultrapure nitric acid, 12 mM H{sub 2}O{sub 2}, and acidified (pH 1.9) ultra-high purity (UHP) water. We measured SAFe (sampling and analysis of Fe) reference seawater samples Surface-1 (0.097 {+-} 0.043 nmol L{sup -1}) and Deep-2 (0.91 {+-} 0.17 nmol L{sup -1}) and obtained results that were in excellent agreement with their DFe consensus values: 0.118 {+-} 0.028 nmol L{sup -1} (n = 7) for Surface-1 and 0.932 {+-} 0.059 nmol L{sup -1} (n = 9) for Deep-2. We also present a vertical DFe profile from the western Weddell Sea collected during the Ice Station Polarstern (ISPOL) ice drift experiment (ANT XXII-2, RV Polarstern) in November 2004-January 2005. The profile shows near-surface DFe concentrations of {approx}0.6 nmol L{sup -1} and bottom water enrichment up to 23 nmol L{sup -1} DFe.

  17. Antioxidant properties of some plants growing wild in Turkey

    Energy Technology Data Exchange (ETDEWEB)

    Serteser, A.; Kargioglu, M.; Gok, V.; Bagci, Y.; Musa Ozcan, M.; Arslan, D.

    2009-07-01

    In this study, the antioxidant activity of 50% aqueous methanol extracts of 38 plants growing in the Afyonkarahisar province of Turkey were evaluated by various antioxidant assay, including free radical scavenging, hydrogen peroxide (H{sub 2}O{sub 2}) scavenging and metal (Fe{sup 2}+) chelating activities. The methanolic fruit extracts of the Cornus and Morus species (H{sub 2}O{sub 2} and DPPH scavenging activities, Fe{sup 2}+ chelating activity) and the methanolic leaf extracts of the Mentha species (DPPH scavenging activities) examined in the assay showed the strongest activities. These antioxidant properties depended on the concentration of samples. (Author) 30 refs.

  18. Iron distribution and histopathological study of the effects of deferoxamine and deferiprone in the kidneys of iron overloaded β-thalassemic mice.

    Science.gov (United States)

    Yatmark, Paranee; Morales, Noppawan Phumala; Chaisri, Urai; Wichaiyo, Surasak; Hemstapat, Warinkarn; Srichairatanakool, Somdet; Svasti, Saovaros; Fucharoen, Suthat

    2016-09-01

    Renal glomerular and tubular dysfunctions have been reported with high prevalence in β-thalassemia. Iron toxicity is implicated in the kidney damage, which may be reversed by iron chelation therapy. To mimic heavy iron overload and evaluate the efficacy of iron chelators in the patients, iron dextran (180mg iron/mouse) was intraperitoneally (i.p.) injected in heterozygous β-globin knockout mice ((muβth-3/+), BKO) and wild type mice (C57BL/6J, WT) over a period of 2 weeks, followed by daily i.p. injection of deferoxamine (DFO) or deferiprone (L1) for 1 week. In BKO mice, iron preferentially accumulated in the proximal tubule with a grading score of 0-1 and increased to grade 3 after iron loading. In contrast, iron mainly deposited in the glomerulus and interstitial space in iron overloaded WT mice. Increased levels of kidney lipid peroxidation, glomerular and medullar damage and fibrosis in iron overloaded mice were reversed by treatment with iron chelators. L1 showed higher efficacy than DFO in reduction of glomerular iron, which was supported by a significantly decreased the amount of glomerular damage. Notably, DFO and L1 demonstrated a distinct pattern of iron distribution in the proximal tubule of BKO mice. In conclusion, chelation therapy has beneficial effects in iron-overloaded kidneys. However, the defect of kidney iron metabolism in thalassemia may be a determining factor of the treatment outcome in individual patients.

  19. Retinal iron homeostasis in health and disease

    Directory of Open Access Journals (Sweden)

    Delu eSong

    2013-06-01

    Full Text Available Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich’s ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD. Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD.

  20. Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

    Science.gov (United States)

    Santos, M A; Esteves, M A; Chaves, S

    2012-01-01

    This review is focused on recent developments on hydroxypyri(mi)dines, as aluminum and actinide chelating agents to combat the toxicity due to accumulations of these metal ions in human body resulting from excessive metal exposure. After a brief update revision of the most common processes of aluminum (Al) exposure, as well as the associated toxicities and pathologies, we will focus on the current available Al chelators and future perspective as potential antidotes of Al toxicity. Due to the similarity between Al and Fe, a major emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators, since they are analogues of the current iron chelators in clinical use (DFP and DFO). This review includes issues such as molecular design strategies and corresponding effects on the associated physico-chemical properties, lipo-hydrophilic balance, toxicity, in vivo bioassays and current clinical applications. The hydroxypyri(mi)dine chelators are also suitable for other hard metal ions, such as the radiotoxic actinides, and so a brief review is included on the applications of these chelators in actinides scavenging.

  1. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

    Directory of Open Access Journals (Sweden)

    Chalmers AW

    2016-02-01

    Full Text Available Anna W Chalmers, Jamile M Shammo Department of Internal Medicine, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelodysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. Keywords: iron chelation therapy, transfusional iron overload, deferasirox

  2. Antioxidant effects of hydroalcoholic and polyphenolic extracts of Peucedanum pastinacifolium Boiss. & Hausskn.

    Science.gov (United States)

    Movahedian, Ahmad; Zolfaghari, Behzad; Mirshekari, Mehrzad

    2016-01-01

    Antioxidant activity of Peucedanum pastinacifolium Boiss. & Hausskn aerial part hydroalcoholic extract (HAE) and polyphenolic extract (PPE) as well as their total phenolic and flavonoid contents were studied. Phenolic and flavonoid contents were respectively estimated as gallic acid and quercetin equivalents. The in vitro antioxidant activity of two extracts of P. pastinacifolium were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), chelating activity on ferrous ions, or ferric reducing antioxidant power (FRAP) assay. In addition, the in vivo antioxidant activity of hydroalcoholic extract was measured by FRAP assay. Total phenolic contents of PPE and HAE were 117.1 ± 6.2 and 44.3 ± 1.7 mg/g, respectively. Total flavonoid content of PPE (43.4 ± 2.1 mg/g) was found to be higher than that of HAE (8.0 ± 1.5 mg/g). In DPPH radical scavenging assay, HAE and PPE showed fifty percent inhibitory concentration (IC50) values of 469.4 ± 9.3 μg/mL and 128.2 ± 5.5 μg/mL, respectively. Iron chelating activity assays indicated IC50 values of 657.5 ± 13.2 μg/mL and 735.4 ± 16.1 μg/mL for HAE and PPE as opposed to ethylenediamine tetra-acetic acid (EDTA) being 16.5 ± 0.8 μg/mL. PPE exhibited greater FRAP value (154.0 ± 1.8 μM) as compared with that of HAE being 69.3 ± 1.4 μM. In animal study, HAE showed a significant (p < 0.05) increase in FRAP level when compared with that of control group. Our results showed that P. pastinacifolium possess antioxidant properties which most likely are exerted through free radical scavenging, chelating activity, and reducing power. PMID:27920823

  3. Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

    Science.gov (United States)

    Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

    2014-01-01

    Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog.

  4. Functional characterization of the chloroplast ferric chelate oxidoreductase enzyme.

    Science.gov (United States)

    Solti, Adám; Müller, Brigitta; Czech, Viktória; Sárvári, Éva; Fodor, Ferenc

    2014-05-01

    Iron (Fe) has an essential role in the biosynthesis of chlorophylls and redox cofactors, and thus chloroplast iron uptake is a process of special importance. The chloroplast ferric chelate oxidoreductase (cFRO) has a crucial role in this process but it is poorly characterized. To study the localization and mechanism of action of cFRO, sugar beet (Beta vulgaris cv Orbis) chloroplast envelope fractions were isolated by gradient ultracentrifugation, and their purity was tested by western blotting against different marker proteins. The ferric chelate reductase (FCR) activity of envelope fractions was studied in the presence of NAD(P)H (reductants) and FAD coenzymes. Reduction of Fe(III)-ethylenediaminetetraacetic acid was monitored spectrophotometrically by the Fe(II)-bathophenanthroline disulfonate complex formation. FCR activity, that is production of free Fe(II) for Fe uptake, showed biphasic saturation kinetics, and was clearly associated only to chloroplast inner envelope (cIE) vesicles. The reaction rate was > 2.5 times higher with NADPH than with NADH, which indicates the natural coenzyme preference of cFRO activity and its dependence on photosynthesis. FCR activity of cIE vesicles isolated from Fe-deficient plants also showed clear biphasic kinetics, where the KM of the low affinity component was elevated, and thus this component was down-regulated.

  5. Antioxidants protect keratinocytes against M. ulcerans mycolactone cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Alvar Grönberg

    Full Text Available BACKGROUND: Mycobacterium ulcerans is the causative agent of necrotizing skin ulcerations in distinctive geographical areas. M. ulcerans produces a macrolide toxin, mycolactone, which has been identified as an important virulence factor in ulcer formation. Mycolactone is cytotoxic to fibroblasts and adipocytes in vitro and has modulating activity on immune cell functions. The effect of mycolactone on keratinocytes has not been reported previously and the mechanism of mycolactone toxicity is presently unknown. Many other macrolide substances have cytotoxic and immunosuppressive activities and mediate some of their effects via production of reactive oxygen species (ROS. We have studied the effect of mycolactone in vitro on human keratinocytes--key cells in wound healing--and tested the hypothesis that the cytotoxic effect of mycolactone is mediated by ROS. METHODOLOGY/PRINCIPAL FINDINGS: The effect of mycolactone on primary skin keratinocyte growth and cell numbers was investigated in serum free growth medium in the presence of different antioxidants. A concentration and time dependent reduction in keratinocyte cell numbers was observed after exposure to mycolactone. Several different antioxidants inhibited this effect partly. The ROS inhibiting substance deferoxamine, which acts via chelation of Fe(2+, completely prevented mycolactone mediated cytotoxicity. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that mycolactone mediated cytotoxicity can be inhibited by deferoxamine, suggesting a role of iron and ROS in mycolactone induced cytotoxicity of keratinocytes. The data provide a basis for the understanding of Buruli ulcer pathology and the development of improved therapies for this disease.

  6. African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

    Institute of Scientific and Technical Information of China (English)

    Olusola Olalekan Elekofehinti; Jean Paul Kamdem; Aline Augusti Bolingon; Margareth Linde Athayde; Seeger Rodrigo Lopes; Emily Pansera Waczuk; Ige Joseph Kade; Isaac Gbadura Adanlawo; Joao Batista Teixeira Rocha

    2013-01-01

    Objective: To evaluate the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore as well as mitochondrial membrane potential (ΔΨm) isolated from rat liver. Methods: Antioxidant activity of SAG was assayed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, iron chelation and ability to inhibit lipid peroxidation in both liver and brain homogenate of rats. Also, the effect of SAG on mitochondrial membrane potential and mitochondrial swelling were determined. Identification and quantification of bioactive polyphenolics was done by HPLC-DAD. Results: SAG exhibited potent and concentration dependent free radical-scavenging activity (IC50/DPPH=275.03±7.8 µg/mL). Reductive and iron chelation abilities also increase with increase in SAG concentration. SAG also inhibited peroxidation of cerebral and hepatic lipids subjected to iron oxidative assault. SAG protected against Ca2+ (110 µmol/L)-induced mitochondrial swelling and maintained theΔΨm. HPLC analysis revealed the presence of gallic acid [(17.54±0.04) mg/g], chlorogenic acid (21.90±0.02 mg/g), caffeic acid (16.64±0.01 mg/g), rutin [(14.71±0.03) mg/g] and quercetin [(7.39±0.05) mg/g]. Conclusions:These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.

  7. Profiling of antioxidant potential and phytoconstituents of Plantago coronopus

    Directory of Open Access Journals (Sweden)

    C. G. Pereira

    Full Text Available Abstract The halophyte species Plantago coronopus has several described ethnomedicinal uses, but few reported biological activities. This work carried out for the first time a comparative analysis of P. coronopus organs in terms of phenolic composition and antioxidant activity of organic and water extracts from roots, leaves and flowers. The leaves contents in selected nutrients, namely amino acids and minerals, are also described. Roots (ethyl acetate and methanol extracts had the highest radical scavenging activity (RSA towards 1,1-diphenyl-2-picrylhydrazyl (DPPH and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS radicals, while leaves (hexane extract had higher RSA on nitric oxide radical and iron chelating ability. High performance liquid chromatography (HPLC analysis identified eighteen phenolics from which salicylic acid and epicatechin are here firstly described in Plantago species. Leaves had mineral levels similar to those of most vegetables, proving to be a good source for elements like calcium, sodium, iron and magnesium, and also for several of the essential amino acids justifying it use as food. Our results, especially those regarding the phenolics composition, can explain the main traditional uses given to this plantain and, altogether, emphasize the potential of P. coronopus as a source of bioactive molecules particularly useful for the prevention of oxidative stress-related diseases.

  8. Antioxidant, pro-oxidant and cytotoxic properties of parsley.

    Science.gov (United States)

    Dorman, H J Damien; Lantto, Tiina A; Raasmaja, Atso; Hiltunen, Raimo

    2011-06-01

    Parsley (Petroselinum crispum) leaves were macerated with a mixture of methanol: water: acetic acid to produce a crude extract which was then defatted with (40°-60°) petrol. Antioxidant activity of the extract was evaluated using a battery of in vitro assays, viz., iron(iii) reduction, iron(ii) chelation and free radical scavenging assays. Evaluation of the pro-oxidant activity of the extract was based upon its effects upon DNA fragmentation and protein carbonylation. Cytotoxicity and apoptotic effects of the extract were determined in non-cancerous CV1-P fibroblast and cancerous A375 melanoma cells using MTT and LDH tests and caspase 3-like activity assay. The highest concentration, 2.0 mg ml(-1), decreased the viability of both cell lines, however, the cancerous melanoma cells were slightly susceptible to the effects. The observed cytotoxicity was not due to the caspase 3 activity. In conclusion, the toxicity might be explained by the pro-oxidative activity of components within the extract against proteins and/or DNA but it is not related to caspase 3-dependent apoptosis within cells.

  9. Arsenic and lead induced free radical generation and their reversibility following chelation.

    Science.gov (United States)

    Flora, S J S; Flora, G; Saxena, G; Mishra, M

    2007-04-15

    Health hazards caused by heavy metals have become a great concern to the population. Lead and arsenic are one of the most important current global environmental toxicants. Their toxic manifestations are being considered caused primarily due to the imbalance between pro-oxidant and antioxidant homeostasis and also due to a high affinity of these metals for thiol groups on functional proteins. They also interfere with a number of other body functions and are known to affect central nervous system (CNS), hematopoietic system, liver and kidneys and produce serious disorders. They produce both acute and chronic poisoning, of which chronic poisoning is more dangerous as its very difficult to revert back to normal condition after chronic exposure to these insidious metals present in our life. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Current approved treatment lies in the administration of chelating agents that forms an insoluble complex with the metal and removes it. They have been used clinically as antidotes for treating acute and chronic poisoning. The most widely used chelating agents are calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA), D-penicillamine and British anti-lewisite (BAL). Meso 2,3 dimercaptosuccinic acid (DMSA), an analogue of BAL, has been tried successfully in animals as well as in humans. But it is unable to remove the metal from intracellular sites. Effective chelation therapy for intoxication by heavy metals depends on whether the chelating agents are able to reach the intracellular site where the heavy metal is firmly bound. One of the important approaches has been the use of combination therapy. This includes use of structurally different chelators or a combination of an adjuvant/ antioxidant/ herbal extracts and a chelator to provide better clinical/ biochemical recovery. A number of other strategies have been suggested to minimize the numerous problems. This

  10. Metal ions, Alzheimer's disease and chelation therapy.

    Science.gov (United States)

    Budimir, Ana

    2011-03-01

    In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

  11. Antioxidant role of amyloid β protein in cell-free and biological systems: implication for the pathogenesis of Alzheimer disease.

    Science.gov (United States)

    Sinha, Maitrayee; Bhowmick, Pritha; Banerjee, Anindita; Chakrabarti, Sasanka

    2013-03-01

    In contrast to many studies showing the pro-oxidative nature of amyloid peptide, this work shows that aggregated Aβ42 peptide in varying concentrations (2-20 μM) in cell-free systems inhibits the formation of hydroxyl radicals and H(2)O(2) from a mixture of iron (20 μM FeSO(4)) and ascorbate (2mM) as measured by benzoate hydroxylation assay and coumarin carboxylic acid assay. Aggregated Aβ42 in similar concentrations further prevents protein and lipid oxidation in isolated rat brain mitochondria incubated alone or with FeSO(4) and ascorbate. Moreover, mitochondria exposed to FeSO(4) and ascorbate show enhanced formation of reactive oxygen species and this phenomenon is also abolished by aggregated Aβ42. It is suggested that the antioxidant property of Aβ42 in various systems is mediated by metal chelation and it is nearly as potent as a typical metal chelator, such as diethylenetriaminepentaacetic acid, in preventing oxidative damage. However, aggregated Aβ42 causes mitochondrial functional impairment in the form of membrane depolarization and a loss of phosphorylation capacity without involving reactive oxygen species in the process. Thus, the present results suggest that the amyloid peptide exhibits a protective antioxidant role in biological systems, but also has toxic actions independent of oxidative stress.

  12. Iron and aluminum in Alzheimer's disease.

    Science.gov (United States)

    Di Lorenzo, Francesco; Di Lorenzo, Berardino

    2013-01-01

    In this case presentation, a woman with high serum levels of aluminum was treated with chelation therapy with deferoxamine and ascorbic acid. This patient was initially bedridden and the clinical situation was complicated by epileptic seizures. After the chelation therapy, the clinical condition was ameliorated and the therapy continued without the correlation to aluminum serum levels. The role of metals in neurodegenerative disorders and the correlation between iron metabolism and amyloid beta peptide are described. This case suggests chelation therapy could represent a promising therapeutic option for this dramatic disease.

  13. Critical evaluation of treatment strategies involving adsorption and chelation for wastewater containing copper, zinc and cyanide

    Energy Technology Data Exchange (ETDEWEB)

    Bose, P.; Bose, M.A.; Kumar, S. [Indian Inst. of Technology, Kanpur (India). Dept Civil Engineering, Environmental Engineering & Management Programme

    2002-11-01

    Industrial wastewater containing heavy metals and cyanide must be treatment for removal of both metals and cyanide before disposal. The study described evaluated treatment strategies involving some indigenous adsorbents and a low-cost chelating agent for treatment of a simulated wastewater containing copper and zinc, complexed with cyanide. Treatment strategies involving three adsorbents, sulfonated coal, biosorbent G. lucidum, and iron oxide coated sand (IOCS), and a chelating agent, insoluble agro-based starch xanthate (IAX), were tested. The evaluation procedure involved comparison of the performance of these treatment strategies with that of conventional treatment. Results indicate that treatment using the chelating agent IAX has the greatest potential as an alternative to the conventional treatment technique. The three adsorbents tested, although reported to be very effective in removing copper and zinc from pure systems, exhibit diminished metal removal capacity in the presence of cyanide, and hence are unsuitable.

  14. Efficient solvent extraction of antioxidant-rich extract from a tropical diatom,Chaetoceros calcitrans (Paulsen) Takano 1968

    Institute of Scientific and Technical Information of China (English)

    Su Chern Foo; Fatimah Md Yusoff; Maznah Ismail; Mahiran Basri; Nicholas Mun Hoe Khong; Kim Wei Chan; Sook Kun Yau

    2015-01-01

    Objective:To compare thein vitro antioxidant capacity of a diatom,Chaetoceros calcitrans (C. calcitrans) extracted using six types of solvents. Methods:Each extract was evaluated in terms of extraction yield, total carotenoid, fucoxanthin content, total phenolic and antioxidant capacities (DPPH• andABTS•+ scavenging activity and iron chelating activity). Results: The methanol extract exhibited the highest yield [(22.71 ± 0.96) g/100 g dry weight (DW)], total carotenoid [(4.46 ± 0.36) mg/g DW], total phenolic [(2.49 ± 0.08) mg gallic acid equivalents/g DW] and second highest fucoxanthin content [(2.08 ± 0.03) mg fucoxanthin/g DW] as compared to other solvent extracts. Methanolic extract also exhibited significantly higher (P Conclusions: Methanol was the recommended solvent for the production of antioxidant rich extract fromC. calcitrans. Both carotenoids and phenolic acids were found to be positively correlated to the antioxidant capacities ofC. calcitrans. Lead bioactives confirmed by subsequent high performance liquid chromatography studies were fucoxanthin, gallic acid and protocatechuic acid.

  15. In vivo skin irritation potential of a Castanea sativa (Chestnut) leaf extract, a putative natural antioxidant for topical application.

    Science.gov (United States)

    Almeida, Isabel F; Valentão, Patrícia; Andrade, Paula B; Seabra, Rosa M; Pereira, Teresa M; Amaral, M Helena; Costa, Paulo C; Bahia, M Fernanda

    2008-11-01

    Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. 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 degrees. The IC(50) found for the iron chelation and DPPH scavenging assays were 132.94 +/- 9.72 and 12.58 +/- 0.54 microg/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.

  16. Mineral Composition, Total Phenol Content and Antioxidant Activity of a Macrolichen Everniastrum cirrhatum (Fr. Hale (Parmeliaceae

    Directory of Open Access Journals (Sweden)

    T. R. Prashith Kekuda

    2011-01-01

    Full Text Available In the present study, we investigated for the first time mineral composition, total phenol content and antioxidant activity of a foliose macrolichen Everniastrum cirrhatum (Fr. Hale (Parmeliaceae from Bhadra wildlife sanctuary, Karnataka, India. Mineral content of the lichen was estimated by Atomic absorption spectrophotometer after acid digestion. The secondary metabolites were detected by thin layer chromatography (TLC and phytochemical assays. The lichen material was extracted with methanol in soxhlet apparatus. Total phenol content was estimated by folin ciocalteu method. Antioxidant activity was determined by DPPH, Ferric reducing and metal chelating assays. Among the principal elements, calcium was found in high concentration followed by magnesium, potassium and phosphorus. Among trace elements, iron was detected in high amount followed by zinc, manganese and copper. The DPPH radical scavenging activity was found to be dose dependent with an IC50 of 6.73 μg/mL. In ferric reducing assay, the absorbance increased with the concentration of extract suggesting reducing power. The extract exhibited good metal chelating activity with an IC50 value of 29.28 μg/mL. Total phenol content was 101.2 mg tannic acid equivalents per gram of extract. Phytochemical analysis revealed the presence of alkaloids, saponins, tannins and terpenoids. TLC revealed atranorin, salazinic acid and protolichesterinic acid. The lichen can be consumed as a source of minerals required for the body as appreciable amount of minerals has been detected. The marked antioxidant activity may be attributed to the presence of phenol content in the extract. Further studies on isolation of metabolites and their bioactivities are under investigation.

  17. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

    DEFF Research Database (Denmark)

    Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della;

    2010-01-01

    patients were chelation-naïve or previously chelated; changes were dependent on dose adjustments and ongoing iron intake. Sustained reductions in labile plasma iron were observed. Discontinuation rate (48.7%) and adverse event profile were consistent with previously reported deferasirox data in MDS...

  18. Deciphering the iron response in Acinetobacter baumannii: A proteomics approach.

    Science.gov (United States)

    Nwugo, Chika C; Gaddy, Jennifer A; Zimbler, Daniel L; Actis, Luis A

    2011-01-01

    Iron is an essential nutrient that plays a role in bacterial differential gene expression and protein production. Accordingly, the comparative analysis of total lysate and outer membrane fractions isolated from A. baumannii ATCC 19606(T) cells cultured under iron-rich and -chelated conditions using 2-D gel electrophoresis-mass spectrometry resulted in the identification of 58 protein spots differentially produced. While 19 and 35 of them represent iron-repressed and iron-induced protein spots, respectively, four other spots represent a metal chelation response unrelated to iron. Most of the iron-repressed protein spots represent outer membrane siderophore receptors, some of which could be involved in the utilization of siderophores produced by other bacteria. The iron-induced protein spots represent a wide range of proteins including those involved in iron storage, such as Bfr, metabolic and energy processes, such as AcnA, AcnB, GlyA, SdhA, and SodB, as well as lipid biosynthesis. The detection of an iron-regulated Hfq ortholog indicates that iron regulation in this bacterium could be mediated by Fur and small RNAs as described in other bacteria. The iron-induced production of OmpA suggests this protein plays a role in iron metabolism as shown by the diminished ability of an isogenic OmpA deficient derivative to grow under iron-chelated conditions.

  19. Antioxidant, antihemolytic and nephroprotective activity of aqueous extract of Diospyros lotus seeds.

    Science.gov (United States)

    Moghaddam, Akbar Hajizadeh; Nabavi, Seyed Mohammad; Nabavi, Seyed Fazel; Bigdellou, Rata; Mohammadzadeh, Sakineh; Ebrahimzadeh, Mohammad Ali

    2012-01-01

    This study was conducted to quantitatively evaluate the antioxidant, antihemolytic and nephroprotective effects of Diospyros lotus seeds extract in experimental in vitro and in vivo models. Antioxidant potential of Diospvyos lotus seeds extract was examined by employing seven in vito models i.e., DPPH, nitric oxide and hydrogen peroxide radicals scavenging activity, iron ion chelating, reducing power and lipid peroxidation through linoleic acid. Antihemolytic activity of extract was examined against hydrogen peroxide-induced erythrocytes hemolysis. Also, nephroprotective effect of extract against gentamicin (GM)-induced renal injury was evaluated. Renal injury was achieved by injecting 100 mg/kg, intraperitoneally (i.p.) of GM in normal saline. Extracts were administrated i.p. in doses 200 and 400 mg/kg. Blood samples were examined for serum creatinine and blood urea nitrogen after 10 consecutive days of treatment. Results show that extract showed different level of antioxidant and antihemolytic activity in the studied models. Also, results show that GM-induced nephrotoxic animal model was successfully constructed. Extract attenuated the gentamicin-induced increase in level of serum creatinine and blood urea nitrogen. The present study shows that the extract offered significant biological action compared with standard compound.

  20. Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

    Science.gov (United States)

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

  1. Which psychosocial factors are related to chelation adherence in thalassemia? A systematic review.

    Science.gov (United States)

    Evangeli, Michael; Mughal, Kulsoom; Porter, John B

    2010-06-01

    Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.

  2. Liver iron content determination by magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Konstantinos; Tziomalos; Vassilios; Perifanis

    2010-01-01

    Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potenti...

  3. Effects of heme iron enriched peptide on iron deficiency anemia in rats.

    Science.gov (United States)

    Tang, Ning; Chen, Le-qun; Zhuang, Hong

    2014-02-01

    The present study aims to investigate whether a daily intake of heme iron enriched peptide obtained from bovine hemoglobin is effective in alleviating iron deficiency anemia (IDA). Wistar rats were randomly divided into six groups: a control group, an anemic group not treated, and anemic groups treated with FeSO4 or with the heme iron enriched peptide at low, moderate or high doses. The rats in the anemic groups were fed on a low-iron diet to establish the iron deficiency anemia model. After the model had been established, different doses of heme iron enriched peptide were given to the rats once a day via intragastric administration. After the iron supplement administration, it was observed that heme iron enriched peptide had effective restorative action returning the hemoglobin, red blood cells, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration and serum iron in IDA animals to normal values or better. In addition, compared with FeSO4, higher Fe bioavailability and fewer side effects were observed. The rats in the moderate dose group had the highest apparent Fe absorption. Moreover, in vivo antioxidant activity was also observed, enhancing the activities of antioxidant enzymes and reduced malondialdehyde levels in IDA rats. Furthermore, the heme iron enriched peptide also exhibited strong in vitro antioxidant activities. In conclusion, heme iron enriched peptide significantly alleviated iron deficiency anemia, and exhibited strong in vitro and in vivo antioxidant activities. This suggests that heme iron enriched peptide might be exploited as a safe, efficient new iron supplement.

  4. Role of iron-mediated free-radical generation in asbestos-induced cytotoxicity.

    Science.gov (United States)

    Brown, R C; Poole, A; Turver, C J; Vann, C

    1987-01-01

    While the in vitro toxicity of mineral fibres is largely determined by the number of long thin fibres present, there are a number of contradictory reports in the literature as to whether the production of oxygen free radicals is also involved and whether the addition of antioxidants or radical scavengers can ameliorate or prevent asbestos-induced cytotoxicity. We report here that crocidolite and other types of amphibole asbestos are less toxic to two cell lines in low oxygen concentrations. The treatment of these fibres with the iron chelator Desferral also reduced the toxicity of the amphiboles. The activity of chrysotile asbestos was not affected by oxygen tension and the cytotoxic effects of Desferral and chrysotile were additive.

  5. Questions and Answers on Unapproved Chelation Products

    Science.gov (United States)

    ... of the marketing scheme to convince consumers to purchase unapproved OTC chelation products. These test kits are ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  6. Antioxidant properties of aqueous extracts from selected lamiaceae species grown in Turkey.

    Science.gov (United States)

    Dorman, H J Damien; Bachmayer, Oliver; Kosar, Müberra; Hiltunen, Raimo

    2004-02-25

    Water-soluble extracts from black thyme (Thymbra spicata L.), savory (Satureja cuneifolia Ten.), Spanish oregano (Coridothymus capitatus (L.) Reichb. f.), sweet marjoram (Majorana hortensis Moench), Syrian oregano (Origanum syriacum L.), Toka oregano (Origanum minutiflorum O. Schwarz et P. H. Davis), and Turkish oregano (Origanum onites L.) were screened for antioxidant properties in a battery of six in vitro assays. Total phenol content and qualitative-quantitative compositional analyses were also carried out. The extracts demonstrated varying degrees of efficacy in each screen. The savory extract was the most effective at reducing iron(III), scavenging 1,1-diphenyl-2-picrylhydrazyl radicals, inhibiting ascorbate-iron(III)-catalyzed hydroxyl radical-mediated brain phospholipid peroxidation, and site-specific hydroxyl radical-mediated 2-deoxy-d-ribose degradation. The Syrian oregano extract was the most effective chelator of iron(II), while Spanish and Turkish oregano extracts were the most effective inhibitors of nonsite-specific hydroxyl radical-mediated 2-deoxy-d-ribose degradation. All the extracts contained Folin-Ciocalteu reagent-reactive substances, which was confirmed by the presence of polar phenolic analytes (i.e., hydroxybenzoates, hydroxycinnamates, and flavonoids).

  7. Importance of insoluble-bound phenolics to antioxidant properties of wheat.

    Science.gov (United States)

    Liyana-Pathirana, Chandrika M; Shahidi, Fereidoon

    2006-02-22

    Two commercial samples of soft (70% Canadian Eastern soft red spring and 30% Canadian Eastern soft white winter) and hard (90% Canadian western hard red spring and 10% Canadian Eastern hard red winter) wheats were used to obtain different milling fractions. Phenolics extracted belonged to free, soluble esters and insoluble-bound fractions. Soluble esters of phenolics and insoluble-bound phenolics were extracted into diethyl ether after alkaline hydrolysis of samples. The content of phenolics was determined using Folin-Ciocalteu's reagent and expressed as ferulic acid equivalents (FAE). The antioxidant activity of phenolic fractions was evaluated using Trolox equivalent antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, reducing power, oxygen radical absorbance capacity, inhibition of oxidation of human low-density lipoprotein cholesterol and DNA, Rancimat, inhibition of photochemilumenescence, and iron(II) chelation activity. The bound phenolic content in the bran fraction was 11.3 +/- 0.13 and 12.2 +/- 0.15 mg FAE/g defatted material for hard and soft wheats, respectively. The corresponding values for flour were 0.33 +/- 0.01 and 0.46 +/- 0.02 mg FAE/g defatted sample. The bound phenolic content of hard and soft whole wheats was 2.1 (+/-0.004 or +/-0.005) mg FAE/g defatted material. The free phenolic content ranged from 0.14 +/- 0.004 to 0.98 +/- 0.05 mg FAE/g defatted milling fractions of hard and soft wheats examined. The contribution of bound phenolics to the total phenolic content was significantly higher than that of free and esterified fractions. In wheat, phenolic compounds were concentrated mainly in the bran tissues. In the numerous in vitro antioxidant assays carried out, the bound phenolic fraction demonstrated a significantly higher antioxidant capacity than free and esterified phenolics. Thus, inclusion of bound phenolics in studies related to quantification and antioxidant activity evaluation of grains and cereals is essential.

  8. Antioxidant activity of ethanolic extract from cultivated strawberries’ leaves (Fragariae folium

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    Stanojević Ljiljana P.

    2015-01-01

    Full Text Available Strawberry is a member of the rose family (Rosaceae, subfamily Rosoideae, tribe Potentilleae in the genus Fragaria. The cultivated varieties of commercial strawberries usually were designated as Fragaria ananassa. Root, leaf, flower and fruit have the healing properties. The strawberry leaves extract is used for blood cleaning, for treatment of oral inflammation, diarrhea, various gastro-intestinal inflammation, and hemorrhoids, as well as a diuretic. So far, many positive biological effects of strawberries (anticancer, antioxidant and anticoagulant effect have been proven. The purpose of this study was to evaluate the antioxidant potential of ethanolic extract from cultivated strawberries (Fragariae folium, varieties Senga Sengana by using different antioxidant assays (DPPH, FRAP, FIC, H2O2 and TBA-MDA. Ethanolic extract from strawberry leaves was obtained by reflux extraction at the boiling temperature. Total phenols and total flavonoids content was determined spectrophotometrically by the method of Folin-Ciocalteu and by method with AlCl3, respectively. In the extract was determined high content of total phenols, while the total flavonoid content is much lower. The concentrations of extract required to neutralize 50% of the initial concentration of DPPH radicals (EC50 after 20 minutes incubation and immediately after adding DPPH radical solution were 7,91 and 19,46 μgcm-3, respectively. Extract was achieved the maximum iron ions chelating ability (67.89% at a concentration of 2 mgcm-3. Inhibition of lipid peroxidation of 70% was achieved by extract concentration of 0.03125 mgcm-3, while the maximum neutralization of H2O2 (30.47% was achieved by extract concentration of 0.5 mgcm-3. FRAP value of the investigated extract is 284.51 mgFe/g of dry extract. Presented results of the antioxidant activity show that the obtained extract from the cultivated strawberry leaves is a potential source of natural antioxidants. [Projekat Ministarstva nauke

  9. SYNTHESIS AND APPLICATION OF IMINOCARBOXYLIC CHELATING FIBERS

    Institute of Scientific and Technical Information of China (English)

    LiHangqiu; ZhouShaoji

    1997-01-01

    In this paper,fibrous chelating exchangers with-N(CH2COOH)2 group have been prepared for the first time by a weakly basic anion exchange fiber (aminated fiber)as the starting materials.The fibers were quite effective for the adsorption of heavy metal ion such as Cu2+.In addition,IR spectrum of the structure of fibers confirms that it is feasible to prepare iminocarboxylic chelating fiber through direct carboxylation reaction.

  10. Structural, Chemical and Biological Aspects of Antioxidants for Strategies Against Metal and Metalloid Exposure

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    Swaran J. S. Flora

    2009-01-01

    Full Text Available Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

  11. Modulation of genotoxic effects in asbestos-exposed primary human mesothelial cells by radical scavengers, metal chelators and a glutathione precursor.

    Science.gov (United States)

    Poser, Ina; Rahman, Qamar; Lohani, Mohtashim; Yadav, Santosh; Becker, Hans-Henner; Weiss, Dieter G; Schiffmann, Dietmar; Dopp, Elke

    2004-04-11

    The genotoxicity of asbestos fibers is generally mediated by reactive oxygen species (ROS) and by insufficient antioxidant protection. To further elucidate which radicals are involved in asbestos-mediated genotoxicity and to which extent, we have carried out experiments with the metal chelators deferoxamine (DEF) and phytic acid (PA), and with the radical scavengers superoxide dismutase (SOD), dimethylthiourea (DMTU) and the glutathione precursor Nacystelyn trade mark (NAL). We investigated the influence of these compounds on the potency of crocidolite, an amphibole asbestos fiber with a high iron content (27%), and chrysotile, a serpentine asbestos fiber with a low iron content (2%), to induce micronuclei (MN) in human mesothelial cells (HMC) after an exposure time of 24-72 h. Our results show that the number of crocidolite-induced MN is significantly reduced after pretreatment of fibers with PA and DEF. This effect was not observed with chrysotile. In contrast, simultaneous treatment of cells with asbestos and the OH*scavenging DMTU or the O2- -scavenging SOD significantly decreased the number of MN induced by chrysotile and crocidolite. In particular, DMTU almost completely suppressed micronucleus induction by both fiber types. A similar effect was observed in the presence of the H(2)O(2)-scavenging NAL after chrysotile treatment of HMC. By means of kinetochore analysis, it could be shown that the number of clastogenic events is decreased after PA and DEF pretreatment of fibers as well as after application of the above-mentioned scavengers. Our results show that chrysotile asbestos induces an increased release of H(2)O(2) in contrast to crocidolite. Also, the iron content of the fiber plays an important role in radical formation, but nevertheless, chrysotile produces oxy radicals to a similar extent as crocidolite, probably by phagocytosis-mediated oxidative bursting.

  12. COMPARATIVE EVALUATION OF ANTIOXIDANT AND ANTIHEMOLYTIC CAPACITIES OF PLANTS OF INDIAN ORIGIN USING MULTIPLE ANTIOXIDANT ASSAYS

    Directory of Open Access Journals (Sweden)

    Deepinderjeet Singh Joshan

    2012-09-01

    Full Text Available The present study is concerned with both in-vitro assessment of antioxidant activity and anti-hemolytic effects of Ficus bengalensis, Calendula officinalis and Juglans regia. Total flavonoids and phenolics also were determined by using aluminum nitrate and Folin–Ciocalteu colorimetric methods respectively. The antioxidant capacity of sample was assessed through reducing power assay, DPPH-scavenging effect,metal chelation assay and superoxide scavenging assay. The extract of Calendula officinalis was found to be more efficient in as antioxidant and anti-hemolytic agents using the in vitro assays as compared to Ficus bengalensis and Juglans regia.

  13. Iron biofortification and homeostasis in transgenic cassava roots expressing an algal iron assimilatory protein, FEA1

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    Uzoma eIhemere

    2012-09-01

    Full Text Available We have engineered the starchy root crop cassava (Manihot esculenta to express the Chlamydomonas reinhardtii iron assimilatory protein, FEA1, in roots to enhance its nutritional qualities. Iron levels in mature cassava storage roots were increased from 10 to 36 ppm in the highest iron accumulating transgenic lines. These iron levels are sufficient to meet the minimum daily requirement for iron in a 500 gm meal. Significantly, the expression of the FEA1 protein did not alter iron levels in leaves. Transgenic plants also had normal levels of zinc in leaves and roots consistent with the specific uptake of iron mediated by the FEA1 protein. Relative to wild-type plants, FEA1 expressing plants had reduced Fe(III chelate reductase activity and gene expression levels consistent with the more efficient uptake of iron in FEA1 transgenic plants. We also show that genes involved in iron homeostasis in cassava have altered tissue-specific patterns of expression in transgenic plants. Steady state transcript levels of the metal-chelate transporter MeYSL1, and the iron storage proteins, MeFER2 and MeFER6, were elevated in various tissues of FEA1 transgenic plants compared to wild-type plants. These results suggest that these gene products play a role in iron translocation and homeostasis in FEA1 transgenic cassava plants. These results are discussed in terms of enhanced strategies for the iron biofortification of plants.

  14. Responses to Iron-Deficiency in Arabidopsis-Thaliana - The Turbo Iron Reductase does not depend on the Formation of Root Hairs and Transfer Cells.

    NARCIS (Netherlands)

    Moog, P.R.; Van der Kooij, T.A.W.; Bruggemann, W.; Schiefelbein, J.W.; Kuiper, P.J.C.

    1995-01-01

    Arabidopsis thaliana (L.) Heynh. Columbia wild type and a root hair-less mutant RM57 were grown on iron-containing and iron-deficient nutrient solutions. In both genotypes, ferric chelate reductase (FCR) of intact roots was induced upon iron deficiency and followed a Michaelis-Menten kinetic with a

  15. Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

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    Singh Rakesh K

    2010-02-01

    Full Text Available Abstract Background Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC, including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19. Methods Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS Results HNTMB displayed high cytotoxicity (IC50 200-400 nM compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM. In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM. In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels. Conclusions The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other

  16. Antioxidant properties of Krebs cycle intermediates against malonate pro-oxidant activity in vitro: a comparative study using the colorimetric method and HPLC analysis to determine malondialdehyde in rat brain homogenates.

    Science.gov (United States)

    Puntel, Robson Luiz; Roos, Daniel Henrique; Grotto, Denise; Garcia, Solange C; Nogueira, Cristina Wayne; Rocha, Joao Batista Teixeira

    2007-06-13

    A variety of Krebs cycle intermediaries has been shown to possess antioxidant properties in different in vivo and in vitro systems. Here we examined whether citrate, succinate, malate, oxaloacetate, fumarate and alpha-ketoglutarate could modulate malonate-induced thiobarbituric acid-reactive species (TBARS) production in rat brain homogenate. The mechanisms involved in their antioxidant activity were also determined using two analytical methods: 1) a popular spectrophotometric method (Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95, 351-358.) and a high performance liquid chromatographic (HPLC) procedure (Grotto, D., Santa Maria, L. D., Boeira, S., Valentini, J., Charão, M. F., Moro, A. M., Nascimento, P. C., Pomblum, V. J., Garcia, S. C., 2006. Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography-visible detection. Journal of Pharmaceutical and Biomedical Analysis 43, 619-624.). Citrate, malate, and oxaloacetate reduced both basal and malonate-induced TBARS production. Their effects were not changed by pre-treatment of rat brain homogenates at 100 degrees C for 10 min. alpha-Ketoglutarate increased basal TBARS without changing malonate-induced TBARS production in fresh and heat-treated homogenates. Succinate reduced basal--without altering malonate-induced TBARS production. Its antioxidant activity was abolished by KCN or heat treatment. Fumarate reduced malonate-induced TBARS production in fresh homogenates; however, its effect was completely abolished by heat treatment. There were minimal differences among the studied methods. Citrate, oxaloacetate, malate, alpha-ketoglutarate and malonate showed iron-chelating activity. We suggest that antioxidant properties of citrate, malate and oxaloacetate were due to their ability to cancel iron redox activity by forming inactive complexes, whereas alpha-ketoglutarate and malonate pro

  17. TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

    Science.gov (United States)

    Kalanaky, Somayeh; Hafizi, Maryam; Safari, Sepideh; Mousavizadeh, Kazem; Kabiri, Mahboubeh; Farsinejad, Alireza; Fakharzadeh, Saideh; Nazaran, Mohammad Hassan

    2016-03-01

    Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

  18. Antioxidant capacity and mineral contents of edible wild Australian mushrooms.

    Science.gov (United States)

    Zeng, X; Suwandi, J; Fuller, J; Doronila, A; Ng, K

    2012-08-01

    Five selected edible wild Australian mushrooms, Morchella elata, Suillus luteus, Pleurotus eryngii, Cyttaria gunnii, and Flammulina velutipes, were evaluated for their antioxidant capacity and mineral contents. The antioxidant capacities of the methanolic extracts of the dried caps of the mushrooms were determined using a number of different chemical reactions in evaluating multi-mechanistic antioxidant activities. These included the Trolox equivalent antioxidant capacity, ferric ion reducing antioxidant power, and ferrous ion chelating activity. Mineral contents of the dried caps of the mushrooms were also determined by inductively coupled plasma-optical emission spectroscopy. The results indicated that these edible wild mushrooms have a high antioxidant capacity and all, except C. gunnii, have a high level of several essential micro-nutrients such as copper, magnesium, and zinc. It can be concluded that these edible wild mushrooms are good sources of nutritional antioxidants and a number of mineral elements.

  19. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models.

    Science.gov (United States)

    Baum, Larry; Ng, Alex

    2004-08-01

    Curcumin is a polyphenolic diketone from turmeric. Because of its anti-oxidant and anti-inflammatory effects, it was tested in animal models of Alzheimer's disease, reducing levels of amyloid and oxidized proteins and preventing cognitive deficits. An alternative mechanism of these effects is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Metals can induce Abeta aggregation and toxicity, and are concentrated in AD brain. Chelators desferrioxamine and clioquinol have exhibited anti-AD effects. Using spectrophotometry, we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+ showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at least two curcumin molecules. The interaction of curcumin with copper reached half-maximum at approximately 3-12 microM copper and exhibited positive cooperativity, with Kd1 approximately 10-60 microM and Kd2 approximately 1.3 microM (for binding of the first and second curcumin molecules, respectively). Curcumin-iron interaction reached half-maximum at approximately 2.5-5 microM iron and exhibited negative cooperativity, with Kd1 approximately 0.5-1.6 microM and Kd2 approximately 50-100 microM. Curcumin and its metabolites can attain these levels in vivo, suggesting physiological relevance. Since curcumin more readily binds the redox-active metals iron and copper than redox-inactive zinc, curcumin might exert a net protective effect against Abeta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB.

  20. NEURODEGENERATION WITH IRON ACCUMULATION TYPE1

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    Shrikhande D Y

    2010-03-01

    Full Text Available Neurodegeneration with iron accumulation type 1 is a rare degenerative disorder presenting with dementia and progressive extrapyramidal dysfunction. A 10 yrs old girl reported with complaints of difficulty in speech and involuntary movements. MRI Brain showed ‘eye of tiger appearance’ which is suggestive of neurodegeneration with iron accumulation type 1. Treatment is symptomatic and chelating agents have no effect. The disease is progressivelyfatal

  1. Antioxidant activity of wheat and buckwheat flours

    Directory of Open Access Journals (Sweden)

    Sedej Ivana J.

    2010-01-01

    Full Text Available Antioxidative activities of wheat flours (type 500 and wholegrain and buckwheat flours (light and wholegrain were tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH·-scavenging activity, reducing power and chelating activity on Fe2+. Also, the content of the total phenolics of ethanolic extracts was estimated. Polyphenolics content (expressed as gallic acid equivalent, GAE in wheat flours varied between 37.1 and 137.2 μg GAE/g extract, while its content in buckwheat flour were at least four time higher and ranged between 476.3 and 618.9μg GAE/g extract. Ethanolic extracts of buckwheat flours exhibited higher antioxidant activities in all the assays, except for chelating activity. Regarding all the obtained results, it can be concluded that bakery products produced with buckwheat flour could be regarded as potential functional foods.

  2. The antioxidant role of xanthurenic acid in the Aedes aegypti midgut during digestion of a blood meal.

    Directory of Open Access Journals (Sweden)

    Vitor L A Lima

    Full Text Available In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA, a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenylthiazol-2-yl] benzenesulfonamide (Ro-61-8048, an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0, a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit.

  3. Chemistry and pharmacological properties of some natural and synthetic antioxidants for heavy metal toxicity.

    Science.gov (United States)

    Flora, S J S; Shrivastava, Rupal; Mittal, Megha

    2013-01-01

    Heavy metals are known to cause oxidative deterioration of bio-molecules by initiating free radical mediated chain reaction resulting in lipid per-oxidation, protein oxidation and oxidation of nucleic acid like DNA and RNA. The development of effective dual functioning antioxidants, possessing both metal-chelating and free radical-scavenging properties should bring into play. Administration of natural and synthetic antioxidants like, quercetin, catechin, taurine, captopril, gallic acid, melatonin, N-acetyl cysteine, α- lipoic acid and others have been recognized in the disease prevention and clinical recovery against heavy metal intoxication. These antioxidants affect biological systems not only through direct quenching of free radicals but also via chelation of toxic metal(s). These antioxidants also, have the capacity to enhance cellular antioxidant defense mechanism by regenerating endogenous antioxidants, such as glutathione and vitamin C and E. They also influence cellular signaling and trigger redox sensitive regulatory pathways. The reactivity of antioxidants in protecting against heavy metal induced oxidative stress depends upon their structural properties, their partitioning abilities between hydrophilic and lipophilic environment and their hydrogen donation antioxidant properties. Herein, we review the structural, biochemical and pharmacological properties of selected antioxidants with particular reference to their ability to (i) chelate heavy metals from its complex (ii) ameliorate free radical (iii) terminate heavy metal induced free radical chain reaction (iv) regenerate endogenous antioxidants and, (v) excretion of metal without its redistribution.

  4. Phytases for Improved Iron Absorption

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Nyffenegger, Christian; Meyer, Anne S.

    2014-01-01

    Microbial phytases (EC 3.1.3.8) catalyse dephosphorylation of phytic acid, which is the primary storage compound for phosphorous in cereal kernels. The negatively charged phosphates in phytic acid chelate iron (Fe3+) and thus retards iron bioavailability in humans 1. Supplementation of microbial...... phytase can improve iron absorption from cereal-based diets 2. In order for phytase to catalyse iron release in vivo the phytase must be robust to low pH and proteolysis in the gastric ventricle. Our work has compared the robustness of five different microbial phytases, evaluating thermal stability......, activity retention, and extent of dephosphorylation of phytic acid in a simulated low pH/pepsin gastric environment. The five phytases responded differently to the robustness parameters: The Peniophora lycii phytase (Ronozyme NP) was the most thermostable, but the least robust enzyme at low pH, whereas...

  5. Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1

    Directory of Open Access Journals (Sweden)

    Simmons Zachary

    2009-02-01

    Full Text Available Abstract Background Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process. Variants of HFE are relatively common in the general population and are most commonly associated with iron overload, but can promote subclinical cellular iron loading even in the absence of clinically identified disease. The effects of the variants as well as the resulting cellular iron dyshomeostasis potentially impact a number of disease-associated pathways. We tested the hypothesis that the two most common HFE variants, H63D and C282Y, would affect cellular secretion of cytokines and trophic factors. Methods We screened a panel of cytokines and trophic factors using a multiplexed immunoassay in human neuroblastoma SH-SY5Y cells expressing different variants of HFE. The influence of cellular iron secretion on the potent chemokine monocyte chemoattractant protein-1 (MCP-1 was assessed using ferric ammonium citrate and the iron chelator, desferroxamine. Additionally, an antioxidant, Trolox, and an anti-inflammatory, minocycline, were tested for their effects on MCP-1 secretion in the presence of HFE variants. Results Expression of the HFE variants altered the labile iron pool in SH-SY5Y cells. Of the panel of cytokines and trophic factors analyzed, only the release of MCP-1 was affected by the HFE variants. We further examined the relationship between iron and MCP-1 and found MCP-1 secretion tightly associated with intracellular iron status. A potential direct effect of HFE is considered because, despite having similar levels of intracellular iron, the association between HFE genotype and MCP-1 expression was different for the H63D and C282Y HFE variants. Moreover, HFE genotype was a factor in the effect of minocycline, a multifaceted antibiotic used in treating a number of neurologic conditions associated with inflammation, on MCP-1

  6. Determination of in vitro total phenolic, flavonoid contents and antioxidant capacity of the methanolic extract of Echium amoenum L.

    Directory of Open Access Journals (Sweden)

    Fathi H

    2016-06-01

    Full Text Available Introduction: In traditional and modern medicine, active ingredients of medicinal plants have many applications in food, pharmaceutical, medical and industry. Antioxidants are compounds that prevent the oxidation process in the cell. Echium amoenum L. is a plant which grows in the mountainous regions of Mazandaran. This plant has different biological effects such as sedation, anti-inflammation, antidepressant and cancer preventive properties in traditional medicine. The aim of this study was to determine the total phenolic, flavonoid contents and antioxidant capacity of the methanolic extract of E.amoenum plant. Methods:In this experimental laboratory study the content of total phenolic Using the folin-siokalatio reactive at 760 nm wavelength and flavonoid With the use of aluminum chloride reagent at 420nm of E.amoenum extract were measured and antioxidant capacities of different concentrations of the extract were evaluated. Results: The results showed that total phenolic content of the extract was 429±2μg gallic acid equivalent/ml and flavonoid content was 148.56±1.52μg quercetin equivalent/ml, respectively. The radical scavenging activity by 2, 2-diphenyl-1-picryl-hydrazyl hydrate (DPPH,inhibitory concentration of 50%(IC50,was determined 178.11 μg/ml. Assessment of the reducing ability of extract showed that the extract had more activity than vitamin C. The percent nitric oxide trap inhibition of the extract was 57.89% and power iron chelating properties was 51.74%,that showed statistically significant difference in comparison with vitamin C and Quercetin (P=0.0473 and (P=0.0096 respectively. Conclusion: According to the results, E.amoenum extract had remarkable antioxidant capacity and can be proposed as an antioxidant compound used in the manufacture of food and pharmaceutical products.

  7. In Vitro Antioxidant Activity Potential of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants

    Directory of Open Access Journals (Sweden)

    Chong Grace-Lynn

    2012-09-01

    Full Text Available Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP, 2,2-diphenyl-1-picryl-hydrazyl (DPPH•, hydroxyl radical (OH•, nitric oxide radical (NO•, superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.

  8. Effect of fermentation on the antioxidant activity in plant-based foods.

    Science.gov (United States)

    Hur, Sun Jin; Lee, Seung Yuan; Kim, Young-Chan; Choi, Inwook; Kim, Geun-Bae

    2014-10-01

    This study provides an overview of the factors that influence the effect of fermentation on the antioxidant activity and the mechanisms that augment antioxidative activities in fermented plant-based foods. The ability of fermentation to improve antioxidant activity is primarily due to an increase in the amount of phenolic compounds and flavonoids during fermentation, which is the result of a microbial hydrolysis reaction. Moreover, fermentation induces the structural breakdown of plant cell walls, leading to the liberation or synthesis of various antioxidant compounds. These antioxidant compounds can act as free radical terminators, metal chelators, singlet oxygen quenchers, or hydrogen donors to radicals. The production of protease, α-amylase and some other enzymes can be influenced by fermentation that may have metal ion chelation activity. Because the mechanisms that affect antioxidant activity during fermentation are extremely varied, further investigation is needed to establish the precise mechanisms for these processes.

  9. Acquisition, transport, and storage of iron by pathogenic fungi.

    Science.gov (United States)

    Howard, D H

    1999-07-01

    Iron is required by most living systems. A great variety of means of acquisition, avenues of uptake, and methods of storage are used by pathogenic fungi to ensure a supply of the essential metal. Solubilization of insoluble iron polymers is the first step in iron assimilation. The two methods most commonly used by microorganisms for solubilization of iron are reduction and chelation. Reduction of ferric iron to ferrous iron by enzymatic or nonenzymatic means is a common mechanism among pathogenic yeasts. Under conditions of iron starvation, many fungi synthesize iron chelators known as siderophores. Two classes of compounds that function in iron gathering are commonly observed: hydroxamates and polycarboxylates. Two major responses to iron stress in fungi are a high-affinity ferric iron reductase and siderophore synthesis. Regulation of these two mechanisms at the molecular level has received attention. Uptake of siderophores is a diverse process, which varies among the different classes of compounds. Since free iron is toxic, it must be stored for further metabolic use. Polyphosphates, ferritins, and siderophores themselves have been described as storage molecules. The iron-gathering mechanisms used by a pathogen in an infected host are largely unknown and can only be posited on the basis of in vitro studies at present.

  10. Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models.

    Science.gov (United States)

    Visavadiya, Nishant P; Soni, Badrish; Dalwadi, Nirav

    2009-01-01

    The aim of present study was to evaluate antioxidant property of Glycyrrhiza glabra root extracts using in vitro models. The dose-dependent aqueous and ethanolic extracts demonstrated the scavenging activity against nitric oxide (concentration that caused 50% inhibition of nitric oxide radicals [IC(50)]=72 and 62.1 microg/ml, respectively), superoxide (IC(50)=64.2 and 38.4 microg/ml, respectively), hydroxyl (IC(50)=81.9 and 63 microg/ml, respectively), DPPH (IC(50)=43.6 and 28.3 microg/ml, respectively) and ABTS(*+) (IC(50)=77.3 and 57.2 microg/ml, respectively) radicals. Further, both extracts showed strong reducing power and iron-chelating capacities. In the Fe(2+)/ascorbate system, both extracts were found to inhibit mitochondrial fraction lipid peroxidation. In copper-catalyzed human serum and low-density lipoprotein oxidation models, both extracts significantly (Pglabra possess considerable antioxidant activity and protective effect against the human lipoprotein oxidative system.

  11. Antioxidant potential of water hyacinth (Eichornia crassipes): In vitro antioxidant activity and phenolic composition

    DEFF Research Database (Denmark)

    Surendraraj, A.; Farvin, Sabeena; Anandan, R.

    2013-01-01

    scavenging ability, iron chelating activity, reducing power, and prevention of oxidation in a liposome model system); and (c) its effectiveness in retarding lipid peroxidation in fish oil by accelerated stability test. Significant differences were observed in total and individual phenolic contents....... Ethanolic extracts of flower, which contained the highest total phenolic content, were found to have high DPPH radical scavenging activity and reducing power. However, ethanolic extracts of leaf exerted a high Fe2+ chelating activity and also inhibited lipid peroxidation process both in liposomes and fish...

  12. Update on the use of deferasirox in the management of iron overload

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-10-01

    Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

  13. Nature of impurities in fertilizers containing EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+) chelates.

    Science.gov (United States)

    Alvarez-Fernández, Ana; Cremonini, Mauro A; Sierra, Miguel A; Placucci, Giuseppe; Lucena, Juan J

    2002-01-16

    Iron chelates derived from ethylenediaminedi(o-hydroxyphenylacetic) acid (EDDHA), ethylenediaminedi(o-hydroxy-p-methylphenylacetic) acid (EDDHMA), ethylenediaminedi(2-hydroxy-5-sulfophenylacetic) acid (EDDHSA), and ethylenediaminedi(5-carboxy-2-hydroxyphenylacetic) acid (EDDCHA) are remarkably efficient in correcting iron chlorosis in plants growing in alkaline soils. This work reports the determination of impurities in commercial samples of fertilizers containing EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+). The active components (EDDHMA/Fe(3+), EDDHSA/Fe(3+), and EDDCHA/Fe(3+)) were separated easily from other compounds present in the fertilizers by HPLC. Comparison of the retention times and the UV-visible spectra of the peaks obtained from commercial EDDHSA/Fe(3+) and EDDCHA/Fe(3+) samples with those of standard solutions showed that unreacted starting materials (p-hydroxybenzenesulfonic acid and p-hydroxybenzoic acid, respectively) were always present in the commercial products. 1D and 2D NMR experiments showed that commercial fertilizers based on EDDHMA/Fe(3+) contained impurities having structures tentatively assigned to iron chelates of two isomers of EDDHMA. These findings suggest that current production processes of iron chelates used in agriculture need to be improved.

  14. The Investigation of Some Bioactive Compounds and Antioxidant Properties of Hawthorn (Crataegus monogyna subsp. monogyna jacq.)

    OpenAIRE

    KESER, Serhat; Celik, Sait; Turkoglu, Semra; YILMAZ, Okkes; Turkoglu, Ismail

    2014-01-01

    Aim: The antioxidant and pharmacological effects of hawthorn have mainly been attributed to the polyphenolic contents. The aim of this research is to determine some bioactive compounds and antioxidant properties of hawthorn aqueous and ethanol extracts of leaves, flowers, and ripened fruits. Materials and Methods: For this purpose, antioxidant activities of extracts were assessed on DPPH•, ABTS•+, superoxide scavenging, reducing power and ferrous metal chelating activity assays and phenolic c...

  15. Ciprofloxacin: a novel therapeutic agent for iron overload?

    Directory of Open Access Journals (Sweden)

    Mitra Elmi

    2009-09-01

    Full Text Available Objective: Major thalassemia is one of the hematological diseases requiring multiple blood transfusions, which results in iron overload in the liver, heart and other organs. Current iron chelation therapy consists of intravenous (IV deferoxamine and oral deferasirox and deferiprone. Although these chelators are effective, many side effects are reported. In the present study, the iron-chelating effect of ciprofloxacin with good oral absorption was investigated. Material and Methods: Thirty male albino Wistar rats were used for the study. Ciprofloxacin (7 or 14 mg/kg per day was administered simultaneously with iron (0.03 g/kg per day or after one-month administration of iron. Ciprofloxacin effect on iron absorption in the liver and heart was studied carefully using atomic absorption. Results: A significant decrease in the liver and heart iron following the ciprofloxacin (14 mg/kg per day administration was observed, when compared with the control group. This ciprofloxacin-induced tissue iron depletion was more pronounced when it was administered simultaneously with iron, when it was administered for a longer duration (2 months rather than 1 month and when it was given in higher doses (14 mg/kg per day. Conclusion: Administration of ciprofloxacin may help to decrease the burden of parenteral administration, thereby improving compliance and also the life expectancy of thalassemic patients.

  16. Cellular iron depletion weakens induction of heme oxygenase-1 by cadmium.

    Science.gov (United States)

    Lai, Chengzhi; Loo, George

    2011-01-01

    Heme oxygenase-1 is an inducible cytoprotective gene, although its induction by environmental factors is not completely understood. This study aimed to ascertain if specific nutritive factors or related compounds influence heme oxygenase-1 expression. In HCT-116 cells, cadmium increased heme oxygenase-1 enzymatic activity. This effect of cadmium was weaker in cells made iron-deficient with the iron chelator, desferrioxamine, which was associated with repression of heme oxygenase-1 protein and mRNA expression. The repression by desferrioxamine of cadmium-induced heme oxygenase-1 upregulation was reversed upon iron replenishment of the cells. Additionally, it was found that thiol antioxidants inhibited the heme oxygenase-1 upregulation caused by cadmium and also by ethacrynic acid, which each decreased intracellular glutathione as did buthionine sulfoxamine. Interestingly, cadmium and ethacrynic acid increased nuclear translocation of Nrf2 and subsequent heme oxygenase-1 expression, but buthionine sulfoxamine did not. Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin, and a superoxide scavenger (Tiron) inhibited cadmium-induced upregulation of heme oxygenase-1. Diphenyleneiodonium was the most potent and inhibited NADPH-cytochrome P450 reductase as well, whereas apocynin and Tiron did not. It is concluded that adequate amounts of iron, which at the atomic level can serve as the pivotal element of heme in NADPH oxidase, must be present in cells to permit what appears to be thiol redox-sensitive, NADPH oxidase-dependent upregulation of heme oxygenase-1. Thus, these findings are significant because they suggest that cells without adequate iron would be unable to fully express the stress gene, heme oxygenase-1, when confronted with the toxic metal, cadmium.

  17. Cytosolic peroxidases protect the lysosome of bloodstream African trypanosomes from iron-mediated membrane damage.

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    Corinna Hiller

    2014-04-01

    Full Text Available African trypanosomes express three virtually identical non-selenium glutathione peroxidase (Px-type enzymes which preferably detoxify lipid-derived hydroperoxides. As shown previously, bloodstream Trypanosoma brucei lacking the mitochondrial Px III display only a weak and transient proliferation defect whereas parasites that lack the cytosolic Px I and Px II undergo extremely fast lipid peroxidation and cell lysis. The phenotype can completely be rescued by supplementing the medium with the α-tocopherol derivative Trolox. The mechanism underlying the rapid cell death remained however elusive. Here we show that the lysosome is the origin of the cellular injury. Feeding the px I-II knockout parasites with Alexa Fluor-conjugated dextran or LysoTracker in the presence of Trolox yielded a discrete lysosomal staining. Yet upon withdrawal of the antioxidant, the signal became progressively spread over the whole cell body and was completely lost, respectively. T. brucei acquire iron by endocytosis of host transferrin. Supplementing the medium with iron or transferrin induced, whereas the iron chelator deferoxamine and apo-transferrin attenuated lysis of the px I-II knockout cells. Immunofluorescence microscopy with MitoTracker and antibodies against the lysosomal marker protein p67 revealed that disintegration of the lysosome precedes mitochondrial damage. In vivo experiments confirmed the negligible role of the mitochondrial peroxidase: Mice infected with px III knockout cells displayed only a slightly delayed disease development compared to wild-type parasites. Our data demonstrate that in bloodstream African trypanosomes, the lysosome, not the mitochondrion, is the primary site of oxidative damage and cytosolic trypanothione/tryparedoxin-dependent peroxidases protect the lysosome from iron-induced membrane peroxidation. This process appears to be closely linked to the high endocytic rate and distinct iron acquisition mechanisms of the infective

  18. ANTIOXIDANT ACTIVITIES AND PHENOLIC PROFILE OF SIX MOROCCAN SELECTED HERBS

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    Madiha Bichra

    2013-02-01

    Full Text Available The present work evaluated the antioxidant capacity of six plants commonly used in traditional Moroccan medicine. The antioxidant capacity was estimated by DPPH test, ferrous ion chelating activity and ABTS test. As results, the highest antioxidant activities were found in Mentha suaveolens, Salvia officinalis and Mentha viridis. Different species showed significant differences in their total phenolic content (TPC. The highest level of phenolics was found in Salvia officinalis and the lowest in Pelargonium roseum. Linear correlation was found between TPC, especially the non-flavonoid content (NFC and the antioxidant activity. Qualitative and quantitative analyzes of major phenolics by reverse-phase high-performance liquid chromatography (RP-HPLC were also performed. On the basis of the obtained results, these studied medicinal herbs were found to serve as a potential source of natural antioxidants due to their richness in phenolic compounds and marked antioxidant activity.

  19. Long-distance signaling of iron deficiency in plants

    OpenAIRE

    2008-01-01

    In a recent issue of the Planta, we established two points regarding the long-distance signal of iron status in tobacco (Nicotiana tabacum L.). One is that the long-distance signal generated in iron deficient tissues is a major factor in positively regulating the expressions of iron uptake genes in tobacco. The expression of a ferric chelate reductase gene (NtFRO1) and an iron-regulated transporter gene (NtIRT1) in roots decreased by cutting off the leaves grown under the iron-deficient condi...

  20. Role of iron in neurodegenerative diseases.

    Science.gov (United States)

    Li, Kai; Reichmann, Heinz

    2016-04-01

    Currently, we still lack effective measures to modify disease progression in neurodegenerative diseases. Iron-containing proteins play an essential role in many fundamental biological processes in the central nervous system. In addition, iron is a redox-active ion and can induce oxidative stress in the cell. Although the causes and pathology hallmarks of different neurodegenerative diseases vary, iron dyshomeostasis, oxidative stress and mitochondrial injury constitute a common pathway to cell death in several neurodegenerative diseases. MRI is capable of depicting iron content in the brain, and serves as a potential biomarker for early and differential diagnosis, tracking disease progression and evaluating the effectiveness of neuroprotective therapy. Iron chelators have shown their efficacy against neurodegeneration in a series of animal models, and been applied in several clinical trials. In this review, we summarize recent developments on iron dyshomeostasis in Parkinson's disease, Alzheimer's disease, Friedreich ataxia, and Huntington's disease.

  1. 地拉罗斯联合顺铂对非小细胞肺癌细胞增殖及凋亡的影响%The effect of combination treatment using iron chelator deferasirox and cisplatin on proliferation and apoptosis in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    袁婷; 梁吉祥; 张斌; 汪蓓蕾; 张欣; 郭刚; 张瑞

    2015-01-01

    Objective To investigate the combination effect using iron chelators deferasirox and cisplatin on A549 cell proliferation and apoptosis and to provide evidences to explore an effective way to treat lung cancer. Methods Lung adeno⁃carcinoma cells were cultured by conventional way, with administration of different concentrations of deferasirox and cisplat⁃in. Cell growth inhibition was observed under an inverted microscope. Proliferation inhibition was evaluated by MTT assay. Morphological changes of cell apoptosis was detected using DAPI,AO/EB straning and flow cytometry. Results After a cer⁃tain time of incubation with different concentrations of the combined drugs,the cell number reduce significantly, which was counted under invert microscope. Cells were dispersed with each other and adherent cells appear shrunken and poor in re⁃fractivity. MTT assay showed that inhibition of cell proliferation was in a concentration-time-dependent manner. Chromatin condensation, nuclear condensation and other typical apoptotic morphology were detected after DAPI and AO/EB straning. Flow cytometry showed that apoptosis increased with rising drug concentration. So combination therapy was significantly pro-apoptotic. Conclusion Deferasirox has the ability to inhibit proliferation of A549 cells and can promote tumor cell apoptosis and enhances cancer cell tolerance when combined with cisplatin. It can also reduce the amount and toxicity of cis⁃platin. It provides a basis for finding an effective way to treat lung cancer.%目的:探讨铁鳌合剂地拉罗斯及其联合顺铂对肺腺癌A549细胞增殖、凋亡的影响,为寻找肺癌有效的治疗途径提供依据。方法常规传代细胞培养方法培养肺腺癌细胞A549,以不同浓度的地拉罗斯、地拉罗斯联合顺铂干预细胞生长一定时间。在倒置显微镜下观察A549的生长抑制特征;MTT法检测细胞的增殖抑制状况;DAPI、AO/EB染色观察细胞

  2. Effect of iron on lipid peroxidation, and enzymatic and non-enzymatic antioxidants and bacoside-A content in medicinal plant Bacopa monnieri L.

    Science.gov (United States)

    Sinha, Sarita; Saxena, Rohit

    2006-03-01

    The effect of Fe was investigated in medicinally important plant, Bacopa monnieri L. and the response on malondialdehyde (MDA) content, superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) was found different in roots and leaves of the metal treated plants. Iron induced stress was observed as indicated by high level of lipid peroxidation, being more steep increase in leaves than roots. In roots, SOD activity was found to increase in metal treated plants except 80 and 160 microM at 72 h, whereas, it decreased in leaves except 10 and 40 microM after 48 h as compared to their respective controls. Among H2O2 eliminating enzymes, POD activity increased in roots, however, it decreased in leaves except at 10 and 40 microM Fe after 48 h as compared to control. At 24 and 48 h, APX activity and ascorbic acid content followed the similar trend and were found to increase in both parts of the metal treated plants as compared to their respective controls. The level of cysteine content in the roots increased at initial period of exposure; however, no marked change in its content was noticed in leaves. In both roots and leaves, non-protein thiol content was found to increase except at higher metal concentrations at 72 h. The data of proline content have shown significant (pbacoside-A (active constituent) content in metal treated plants increases, therefore, it is advisable to assess the biological activity of the plants before using for medicinal purposes, particularly in developing countries.

  3. Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Bayanzay K

    2016-08-01

    Full Text Available Karim Bayanzay, Lama Alzoebie Department of Hematology, Gulf Medical University, Ajman, United Arab Emirates Abstract: Hypertransfusion regimens for thalassemic patients revolutionized the management of severe thalassemia; transforming a disease which previously led to early infant death into a chronic condition. The devastating effect of the accrued iron from chronic blood transfusions necessitates a more finely tuned approach to limit the complications of the disease, as well as its treatment. A comprehensive approach including carefully tailored transfusion protocol, continuous monitoring and assessment of total body iron levels, and iron chelation are currently the mainstay in treating iron overload. There are also indications for ancillary treatments, such as splenectomy and fetal hemoglobin induction. The main cause of death in iron overload continues to be related to cardiac complications. However, since the widespread use of iron chelation started in the 1970s, there has been a general improvement in survival in these patients. Keywords: hematology, chelators, deferoxamine, deferiserox, deferiprone, liver iron concentration, iron overload, serum ferritin concentration, hepatic iron storage, iron chelation therapy

  4. Differing features of proteins in membranes may result in antioxidant or prooxidant action: opposite effects on lipid peroxidation of alcohol dehydrogenase and albumin in liposomal systems.

    Science.gov (United States)

    Riedl, A; Shamsi, Z; Anderton, M; Goldfarb, P; Wiseman, A

    1996-02-01

    The influence of 3 thiol-containing compounds, bovine serum albumin (fatty acid free: BSA), glutathione (GSH) and yeast alcohol dehydrogenase (YADH) on lipid peroxidation in multilamellar liposomes, prepared from ox-brain phospholipid, was investigated. Thiol-compounds were added either before liposome formation, or after liposome formation; and their effects compared to a positive control. Bovine serum albumin (BSA), an acidic hydrophilic protein, displays a small, concentration dependent, antioxidant effect when added to preformed liposomes. A much larger antioxidant effect was observed when the BSA was entrapped inside the liposome, by adding BSA just prior to liposome preparation. In contrast, a Zn(2+) containing redox enzyme, YADH, a basic hydrophobic membrane-associating protein, displays a large pro-oxidant effect at much lower concentrations especially when entrapped inside the liposome. This was observed also with GSH; but per mole of -SH, YADH was about 18 times as powerful a pro-oxidant perhaps because of structural changes to the membrane. Oxidized glutathione and N-acetylcysteine were also pro-oxidant (cysteine and cystine showed little effect). Formation of thiyl radicals may occur in the presence of iron ions with these pro-oxidant sulphur-containing compounds. Partial protection against lipid peroxidation was observed with EDTA, desferrioxamine and protoporphyrin (IX), potent iron-chelating agents.

  5. Demetalation of Fe, Mn, and Cu chelates and complexes: application to the NMR analysis of micronutrient fertilizers.

    Science.gov (United States)

    López-Rayo, Sandra; Lucena, Juan J; Laghi, Luca; Cremonini, Mauro A

    2011-12-28

    The application of nuclear magnetic resonance (NMR) for the quality control of fertilizers based on Fe(3+), Mn(2+), and Cu(2+) chelates and complexes is precluded by the strong paramagnetism of metals. Recently, a method based on the use of ferrocyanide has been described to remove iron from commercial iron chelates based on the o,o-EDDHA [ethylenediamine-N,N'bis(2-hydroxyphenylacetic)acid] chelating agent for their analysis and quantification by NMR. The present work extended that procedure to other paramagnetic ions, manganese and copper, and other chelating, EDTA (ethylenediaminetetraacetic acid), IDHA [N-(1,2-dicarboxyethyl)-d,l-aspartic acid], and complexing agents, gluconate and heptagluconate. Results showed that the removal of the paramagnetic ions was complete, allowing us to obtain (1)H NMR spectra characterized by narrow peaks. The quantification of the ligands by NMR and high-performance liquid chromatography showed that their complete recovery was granted. The NMR analysis enabled detection and quantification of unknown impurities without the need of pure compounds as internal standards.

  6. Influence of Chelating Agents on Chromium Fate in Sediment

    Institute of Scientific and Technical Information of China (English)

    WANGXIAOCHANG; SUNJINHE; 等

    1996-01-01

    A laboratory investigation on reaction between chelating agents and chromium was conducted to evaluate the effect of chelating agents on the adsorption and desorption of chromium in sediment.The amount of adsorbed chromium(VI) in sediment decreased slightly by 5%-10% because of addition of chelating agents.Chelating agents inhibited the removal of Cr(Ⅲ)by sediment from solutions and the inhibiting effect was in the order:citric acid>tartaric acid>EDTA,Salicylic acid.No effect of chelating agents on desorption of chromium in sediment was observed.

  7. Federal regulation of unapproved chelation products.

    Science.gov (United States)

    Lee, Charles E

    2013-12-01

    Chelation products can be helpful in the treatment of metal poisoning. However, many unapproved products with unproven effectiveness and safety are marketed to consumers, frequently via the internet. This paper describes the primary responsibility of the Health Fraud and Consumer Outreach Branch of the United States Food and Drug Administration to identify and address health fraud products. Efforts to prevent direct and indirect hazards to the population's health through regulatory actions are described.

  8. Deferasirox and deferiprone remove cardiac iron in the iron-overloaded gerbil

    Science.gov (United States)

    WOOD, JOHN C.; OTTO-DUESSEL, MAYA; GONZALEZ, IGNACIO; AGUILAR, MICHELLE I.; SHIMADA, HIRO; NICK, HANSPETER; NELSON, MARVIN; MOATS, REX

    2010-01-01

    Introduction Deferasirox effectively controls liver iron concentration; however, little is known regarding its ability to remove stored cardiac iron. Deferiprone seems to have increased cardiac efficacy compared with traditional deferoxamine therapy. Therefore, the relative efficacy of deferasirox and deferiprone were compared in removing cardiac iron from iron-loaded gerbils. Methods Twenty-nine 8- to 10-week-old female gerbils underwent 10 weekly iron dextran injections of 200 mg/kg/week. Prechelation iron levels were assessed in 5 animals, and the remainder received deferasirox 100 mg/kg/D po QD (n = 8), deferiprone 375 mg/kg/D po divided TID (n = 8), or sham chelation (n = 8), 5 days/week for 12 weeks. Results Deferasirox reduced cardiac iron content 20.5%. No changes occurred in cardiac weight, myocyte hypertrophy, fibrosis, or weight-to-dry weight ratio. Deferasirox treatment reduced liver iron content 51%. Deferiprone produced comparable reductions in cardiac iron content (18.6% reduction). Deferiprone-treated hearts had greater mass (16.5% increase) and increased myocyte hypertrophy. Deferiprone decreased liver iron content 24.9% but was associated with an increase in liver weight and water content. Conclusion Deferasirox and deferiprone were equally effective in removing stored cardiac iron in a gerbil animal model, but deferasirox removed more hepatic iron for a given cardiac iron burden. PMID:17145573

  9. Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Assis, Reijâne Alves de; Kassab, Carolina; Seguro, Fernanda Salles [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Costa, Fernando Ferreira [Universidade Estadual de Campinas, Campinas, SP (Brazil); Silveira, Paulo Augusto Achucarro [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Wood, John [University of Southern California, California (United States); Hamerschlak, Nelson [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2013-07-01

    To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

  10. Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology

    Directory of Open Access Journals (Sweden)

    Christina N. Kontoghiorghe

    2015-11-01

    Full Text Available Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό—plant, chele (χηλή—claw of the crab with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.

  11. Effects of Tissue Culture and Mycorrhiza Applications in Organic Farming on Concentrations of Phytochemicals and Antioxidant Capacities in Ginger (Zingiber officinale Roscoe) Rhizomes and Leaves.

    Science.gov (United States)

    Min, Byungrok R; Marsh, Lurline E; Brathwaite, Keegan; Daramola, Adebola O

    2017-02-23

    Tissue culture and mycorrhiza applications can provide disease-free seedlings and enhanced nutrient absorption, respectively, for organic farming. Ginger (Zingiber officinale Roscoe) is rich in phytochemicals and has various health-protective potentials. This study was aimed at determining effects of tissue culture and mycorrhiza applications alone or in combinations in organic farming on phytochemical contents (total phenolics and flavonoids [TP and TF, respectively], gingerol and shogaol homologues, phenolic acids, and carotenoids) and antioxidant capacities (DPPH [2,2-diphenyl-1-picrylhydrazyl] radical scavenging, oxygen radical absorbance (ORAC), and iron-chelating capacities [ICC]) in solvent-extractable (Free) and cell-wall-matrix-bound (Bound) fractions of ginger rhizome and Free fraction of the leaves in comparison with non-organics. Concentrations of the phytochemicals and antioxidant capacities, except for carotenoids and ICC, were significantly higher in organic ginger rhizomes and leaves than in non-organics regardless of the fractions and treatments (P organic farming significantly increased levels of TP, TF, gingerols, and ORAC in the Free fraction of the rhizome (P organic farming with mycorrhiza and tissue culture applications can increase concentrations of phytochemicals and antioxidant capacities in ginger rhizomes and leaves and therefore improve their health-protective potentials.

  12. Parkinson's Disease: The Mitochondria-Iron Link.

    Science.gov (United States)

    Muñoz, Yorka; Carrasco, Carlos M; Campos, Joaquín D; Aguirre, Pabla; Núñez, Marco T

    2016-01-01

    Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson's disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences-mitochondrial dysfunction, iron accumulation, and oxidative damage-generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson's disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation-by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways-is a viable therapy for retarding this cycle.

  13. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders.

    Science.gov (United States)

    de Swart, Louise; Hendriks, Jan C M; van der Vorm, Lisa N; Cabantchik, Z Ioav; Evans, Patricia J; Hod, Eldad A; Brittenham, Gary M; Furman, Yael; Wojczyk, Boguslaw; Janssen, Mirian C H; Porter, John B; Mattijssen, Vera E J M; Biemond, Bart J; MacKenzie, Marius A; Origa, Raffaella; Galanello, Renzo; Hider, Robert C; Swinkels, Dorine W

    2016-01-01

    Non-transferrin-bound iron and its labile (redox active) plasma iron component are thought to be potentially toxic forms of iron originally identified in the serum of patients with iron overload. We compared ten worldwide leading assays (6 for non-transferrin-bound iron and 4 for labile plasma iron) as part of an international inter-laboratory study. Serum samples from 60 patients with four different iron-overload disorders in various treatment phases were coded and sent in duplicate for analysis to five different laboratories worldwide. Some laboratories provided multiple assays. Overall, highest assay levels were observed for patients with untreated hereditary hemochromatosis and β-thalassemia intermedia, patients with transfusion-dependent myelodysplastic syndromes and patients with transfusion-dependent and chelated β-thalassemia major. Absolute levels differed considerably between assays and were lower for labile plasma iron than for non-transferrin-bound iron. Four assays also reported negative values. Assays were reproducible with high between-sample and low within-sample variation. Assays correlated and correlations were highest within the group of non-transferrin-bound iron assays and within that of labile plasma iron assays. Increased transferrin saturation, but not ferritin, was a good indicator of the presence of forms of circulating non-transferrin-bound iron. The possibility of using non-transferrin-bound iron and labile plasma iron measures as clinical indicators of overt iron overload and/or of treatment efficacy would largely depend on the rigorous validation and standardization of assays.

  14. Targeting Iron Acquisition Blocks Infection with the Fungal Pathogens Aspergillus fumigatus and Fusarium oxysporum

    Science.gov (United States)

    Leal, Sixto M.; Roy, Sanhita; Vareechon, Chairut; Carrion, Steven deJesus; Clark, Heather; Lopez-Berges, Manuel S.; diPietro, Antonio; Schrettl, Marcus; Beckmann, Nicola; Redl, Bernhard; Haas, Hubertus; Pearlman, Eric

    2013-01-01

    Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo. Conversely, we show that exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in infected mice. By examining mutant Aspergillus and Fusarium strains, we found that fungal transcriptional responses to low iron levels and extracellular siderophores are essential for fungal growth during infection. Further, we showed that targeting fungal iron acquisition or siderophore biosynthesis by topical application of iron chelators or statins reduces fungal growth in the cornea by 60% and that dual therapy with the iron chelator deferiprone and statins further restricts fungal growth by 75%. Together, these studies identify specific host iron-chelating and fungal iron-acquisition mediators that regulate fungal growth, and demonstrate that therapeutic inhibition of fungal iron acquisition can be utilized to treat topical fungal infections. PMID:23853581

  15. [Genetic iron overloads and hepatic insulin-resistance iron overload syndrome: an update].

    Science.gov (United States)

    Ruivard, M

    2009-01-01

    Hepcidin inhibits intestinal absorption of iron through internalisation of ferroportin. Its discovery helps to better understand the genetic iron overloads. The insulin resistance-hepatic iron overload (IR-HIO)--also coined as the dysmetabolic iron overload syndrome--is a common cause or iron overload. This article is a review about genetic iron overloads and IR-HIO. Type 1 haemochromatosis C282Y +/+ accounts for 95% of the haemochromatosis. Hepatic fibrosis may develop if serum ferritin is higher than 1000 microg/l but can be partially reversible with phlebotomies. Juvenile haemochromatosis (type 2) and type 3 haemochromatosis (mutation of the transferrin receptor 2) are very uncommon. Several mutations of the ferroportin gene can cause usually mild iron overload of autosomal dominant inheritance. Aceruleoplasminemia is an uncommon disorder involving cerebral iron overload. The causes and consequences of the IR-HIO are unknown. Treatment of IR-HIO is focused on metabolic syndrome and phlebotomies are questionable because the overload is moderate and intestinal absorption of iron seems to be low. MRI (or other non invasive methods) is needed to truly assess iron overload because serum ferritin overestimates it in metabolic syndrome. Several points have to be elucidated: how HFE interferes with hepcidin in type 1 haemochromatosis; the causes of variability of iron overload; the benefits of populations screening; the advantage of phlebotomies in IR-HIO; the use of new oral iron chelators.

  16. Characterization of new specific copper chelators as potential drugs for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Michel; Robert, Anne; Sournia-Saquet, Alix; Vendier, Laure; Meunier, Bernard

    2014-05-26

    The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8-aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu(2+) with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu(2+) from a metal-loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu(2+) compared with Cu(+). Consequently, the copper ion is easily released from the bis(8-aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)2] in reductive conditions. The catalytic production of H2O2 by [Cu(2+)-Aβ(1-28)]/ascorbate is inhibited in vitro by the bis(8-aminoquinoline) 1, suggesting that 1 should be able to play a protective role against oxidative damages induced by copper-loaded amyloids.

  17. Macrophage preconditioning with synthetic malaria pigment reduces cytokine production via heme iron-dependent oxidative stress.

    Science.gov (United States)

    Taramelli, D; Recalcati, S; Basilico, N; Olliaro, P; Cairo, G

    2000-12-01

    Hemozoin (malaria pigment), a polymer of hematin (ferri-protoporphyrin IX) derived from hemoglobin ingested by intraerythrocytic plasmodia, modulates cytokine production by phagocytes. Mouse peritoneal macrophages (PM) fed with synthetic beta-hematin (BH), structurally identical to native hemozoin, no longer produce tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) in response to lipopolysaccharide (LPS). Impairment of NO synthesis is due to inhibition of inducible nitric oxide synthase (iNOS) production. BH-mediated inhibition of PM functions cannot be ascribed to iron release from BH because neither prevention by iron chelators nor down-regulation of iron-regulatory protein activity was detected. Inhibition appears to be related to pigment-induced oxidative stress because (a) thiol compounds partially restored PM functions, (b) heme oxygenase (HO-1) and catalase mRNA levels were up-regulated, and (c) free radicals production increased in BH-treated cells. The antioxidant defenses of the cells determine the response to BH: microglia cells, which show a lower extent of induction of HO-1 and catalase mRNAs and lower accumulation of oxygen radicals, are less sensitive to the inhibitory effect of BH on cytokine production. Results indicate that BH is resistant to degradation by HO-1 and that heme-iron mediated oxidative stress may contribute to malaria-induced immunosuppression. This study may help correlate the different clinical manifestations of malaria, ranging from uncomplicated to severe disease, with dysregulation of phagocyte functions and promote better therapeutic strategies to counteract the effects of hemozoin accumulation.

  18. Iron, anemia and hepcidin in malaria

    Directory of Open Access Journals (Sweden)

    Natasha eSpottiswoode

    2014-05-01

    Full Text Available Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to coinfections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world.

  19. Simultaneous Determination of Chelating Agents by Ion-Suppression and Ion-Pair Chromatography in Wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Dodi, Alain; Bouscarel, Maelle [Commissariat a l' energie atomique - C.E.A, Centre d' Etude de Cadarache, Laboratoire d' Analyses Radiochimiques et Chimiques, St Paul lez Durance (France)

    2008-07-01

    This article describes two methods for analysing chelating agents found in nuclear waste. First, ion-suppression chromatography using an anion exchange stationary phase and mobile phase consisting of a nitric acid solution and pure water gradient. UV detection was performed at 330 nm after the reaction with a post-column reagent composed of iron nitrate in perchloric acid. Secondly, ion-pair chromatography with a mobile phase consisting of a mixture of nitric acid, tetra-butyl-ammonium hydrogeno-sulphate, tetra-butyl-ammonium hydroxide and iron chloride. A reversed-phase material was used as a stationary phase and detection was performed by direct measurement of the UV absorption at 260 nm. The quantification limits were lower for ion-pair chromatography than for ion-suppression chromatography. Both methods were easy to implement and allow a multi-element separation in less than 30 min with low detection limits. (authors)

  20. Novel Terbium Chelate Doped Fluorescent Silica Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Ning Qiaoyu; Meng Jianxin; Wang Haiming; Liu Yingliang; Man Shiqing

    2006-01-01

    Novel terbium chelate doped silica fluorescent nanoparticles were prepared and characterized.The preparation was carried out in water-in-oil (W/O) microemulsion containing monomer precursor (pAB-DTPAA-APTEOS), Triton X-100, n-hexanol, and cyclohexane by controlling copolymerization of tetraethyl orthosilicate and 3-aminopropyl-triethyloxysilane.The nanoparticles are spherical and uniform in size, about 30 nm in diameter, strongly fluorescent, and highly stable.The amino groups directly introduced to the surface of the nanoparticles using APTEOS during preparation made the surface modification and bioconjugation of the nanoparticles easier.The nanoparticles are expected as an efficient time-resolved luminescence biological label.

  1. Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease.

    Science.gov (United States)

    Bogdan, Alexander R; Miyazawa, Masaki; Hashimoto, Kazunori; Tsuji, Yoshiaki

    2016-03-01

    Iron is necessary for life, but can also cause cell death. Accordingly, cells evolved a robust, tightly regulated suite of genes for maintaining iron homeostasis. Previous mechanistic studies on iron homeostasis have granted insight into the role of iron in human health and disease. We highlight new regulators of iron metabolism, including iron-trafficking proteins [solute carrier family 39, SLC39, also known as ZRT/IRT-like protein, ZIP; and poly-(rC)-binding protein, PCBP] and a cargo receptor (NCOA4) that is crucial for release of ferritin-bound iron. We also discuss emerging roles of iron in apoptosis and a novel iron-dependent cell death pathway termed 'ferroptosis', the dysregulation of iron metabolism in human pathologies, and the use of iron chelators in cancer therapy.

  2. Regulation of iron absorption in hemoglobinopathies.

    Science.gov (United States)

    Rechavi, Gideon; Rivella, Stefano

    2008-11-01

    Beta-thalassemia and sickle cell anemia (SCD) represent the most common hemoglobinopathies caused, respectively, by deficient production or alteration of the beta chain of hemoglobin (Hb). Patients affected by the most severe form of thalassemia suffer from profound anemia that requires chronic blood transfusions and chelation therapies to prevent iron overload. However, patients affected by beta-thalassemia intermedia, a milder form of the disease that does not require chronic blood transfusions, eventually also show elevated body iron content due to increased gastrointestinal iron absorption. Even SCD patients might require blood transfusions and iron chelation to prevent deleterious and painful vaso-occlusive crises and complications due to iron overload. Although definitive cures are presently available, such as bone marrow transplantation (BMT), or are in development, such as correction of the disease through hematopoietic stem cell beta-globin gene transfer, they are potentially hazardous procedures or too experimental to provide consistently safe and predictive clinical outcomes. Therefore, studies that aim to better understand the pathophysiology of the hemoglobinopathies might provide further insight and new drugs to dramatically improve the understanding and current treatment of these diseases. This review will describe how recent discoveries on iron metabolism and erythropoiesis could lead to new therapeutic strategies and better clinical care of these diseases, thereby yielding a much better quality of life for the patients.