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Sample records for iron chelating agents

  1. Iron Chelation

    MedlinePlus

    ... iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you have ... may want to perform: How quickly does iron overload happen? This is different for each person. It ...

  2. Using iron chelating agents to enhance dermatological PDT

    NASA Astrophysics Data System (ADS)

    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.

  3. Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent

    PubMed Central

    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

  4. Use of Iron Chelating Agents in Transfusion Dependent Thalassaemia Major Patients.

    PubMed

    Santra, S; Bhattacharya, A; Mukhopadhyay, T; Agrawal, D; Kumar, S; Das, P; Chakrabarty, P

    2015-10-01

    This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.

  5. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  6. Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils

    PubMed Central

    Völlger, Lena; Akong-Moore, Kathryn; Cox, Linda; Goldmann, Oliver; Wang, Yanming; Schäfer, Simon T.; Naim, Hassan Y.; Nizet, Victor; von Köckritz-Blickwede, Maren

    2016-01-01

    Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone–DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity. PMID:27129288

  7. Iron Chelators as Potential Therapeutic Agents for Parkinson’s Disease

    PubMed Central

    Perez, Carlos A.; Tong, Yong; Guo, Maolin

    2009-01-01

    Parkinson’s disease (PD) is a neurological disorder characterized by the progressive impairment of motor skills in patients. Growing evidence suggests that abnormal redox-active metal accumulation, caused by dysregulation, plays a central role in the neuropathology of PD. Redox-active metals (e.g. Fe and Cu) catalyze essential reactions for brain function. However, these metals can also participate in the generation of highly toxic free radicals that can cause oxidative damage to cells and ultimately lead to the death of dopamine-containing neurons. The emergence of redox-active metals as key players in the pathogenesis of PD strongly suggests that metal-chelators could be beneficial in the treatment of this condition. This mini-review summarizes major recent developments on natural, synthetic iron chelating compounds and hydrogen peroxide-triggered prochelators as potential candidates for PD treatment. PMID:19809592

  8. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  9. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  10. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  11. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  12. Synthesis and biological evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents

    PubMed Central

    Saghaie, L.; Sadeghi-aliabadi, H.; Kafiri, M.

    2011-01-01

    A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (Kpart) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC50 of HPOs was determined using MTT assay. Among these ligands, compound 4e (Kpart=5.02) with an IC50 of 30 μM and 4f (Kpart=0.1) with an IC50 of 700 μM showed the lowest and highest IC50s, respectively. In conclusion, the introduction of a more hydrophobic functional group (such as butyl in compound 4e) on the nitrogen of pyridinone ring resulted in higher cytotoxic activity of ligands. PMID:22224095

  13. Macrocyclic bifunctional chelating agents

    DOEpatents

    Meares, Claude F.; DeNardo, Sally J.; Cole, William C.; Mol, Min K.

    1987-01-01

    A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.

  14. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    DOEpatents

    Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

    2005-01-25

    The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  15. Benzyl and Methyl Fatty Hydroxamic Acids Based on Palm Kernel Oil as Chelating Agent for Liquid-Liquid Iron(III) Extraction

    PubMed Central

    Haron, Md Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Rafiee-Moghaddam, Roshanak; Mahdavi, Behnam; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh

    2012-01-01

    Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO3 and H2SO4. The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III). PMID:22408444

  16. Iron chelation and multiple sclerosis

    PubMed Central

    Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

    2014-01-01

    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. PMID:24397846

  17. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  18. Biological activities of pyochelins: iron-chelating agents of Pseudomonas aeruginosa.

    PubMed Central

    Liu, P V; Shokrani, F

    1978-01-01

    Strains of Pseudomonas aeruginosa able to grow readily in serum (serum resistant) produce siderophores in large quantity, enabling them to extract iron from transferrins. The term pyochelin has been proposed for this group of compounds. Pyochelin extractable with ethyl acetate and designated pyochelin A appears to be a mixture of catechols and other phenolates. The structures of water-soluble siderophores, designated pyochelin B, have not been determined. Pyochelins enabled growth in serum of strains of serum-sensitive P. aeruginosa and other gram-negative bacilli. Serum-resistant strains of P. aeruginosa tended to be more virulent than equally toxigenic strains of the serum-sensitive group. However, incorporation of pyochelins into the inocula of serum-sensitive strains could reduce, rather than enhance, their virulence. Utilization of pyochelins by serum-sensitive strains of P. aeruginosa rendered some of these organisms resistant to pyocins which were otherwise lethal to them. Images PMID:103839

  19. Novel polycatecholamide chelating agents

    DOEpatents

    Weitl, F.L.; Raymond, K.N.

    1981-08-24

    Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. Formulas of the compounds are given. To prepare them polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO/sub 3/H, SO/sub 3/M, NO/sub 2/, CO/sub 2/H or CO/sub 2/M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr/sub 3/ or BCl/sub 3/ in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated.

  20. Polycatecholamide chelating agents

    DOEpatents

    Weitl, F.L.; Raymond, K.N.

    1984-04-10

    Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula given in patent. Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO[sub 3]H, SO[sub 3]M, NO[sub 2], CO[sub 2]H or CO[sub 2]M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr[sub 3] or BCl[sub 3] in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated. No Drawings

  1. Polycatecholamide chelating agents

    DOEpatents

    Weitl, Frederick L.; Raymond, Kenneth N.

    1984-01-01

    Novel polybenzamide compounds useful for in vitro or in vivo chelation are described. The compounds have the formula ##STR1## Polyamines are reacted with 2,3-dimethoxy benzoyl chloride unsubstituted or substituted with SO.sub.3 H, SO.sub.3 M, NO.sub.2, CO.sub.2 H or CO.sub.2 M as desired is reacted with a polyamine in an inert solvent then demethylated with BBr.sub.3 or BCl.sub.3 in an inert solvent. Where compounds symmetrically substituted on the terminal N's are desired, the polyamine is first reductively alkylated by reaction with an aldehyde or ketone and the resulting Schiff base is hydrogenated.

  2. An Evaluation of the Chelating Agent EDDS for Marigold Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) ligands (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 plants. The offsite runoff and contamina...

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

    PubMed Central

    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

  4. Natural chelating agents for radionuclide decorporation

    DOEpatents

    Premuzic, Eugene T.

    1988-01-01

    This invention relates to the preparation of new, naturally produced chelating agents as well as to the method and resulting chelates of desorbing cultures in a bioavailable form involving Pseudomonas species or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 100-1,000 and also forms chelates with uranium of molecular weight in the area of 100-1,000 and 1,000-2,000.

  5. Regional siderosis: a new challenge for iron chelation therapy

    PubMed Central

    Cabantchik, Zvi Ioav; Munnich, Arnold; Youdim, Moussa B.; Devos, David

    2013-01-01

    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 of dual activity, one 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 functions. PMID:24427136

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

    PubMed Central

    Veríssimo, Monica Pinheiro de Almeida; Loggetto, Sandra Regina; Fabron Junior, Antonio; Baldanzi, Giorgio Roberto; Hamerschlak, Nelson; Fernandes, Juliano Lara; Araujo, Aderson da Silva; Lobo, Clarisse Lopes de Castro; Fertrin, Kleber Yotsumoto; Berdoukas, Vasilios Antonios; Galanello, Renzo

    2013-01-01

    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. PMID:24478610

  7. Iron-chelating compound from Mycobacterium avium.

    PubMed Central

    McCullough, W G; Merkal, R S

    1976-01-01

    A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine. PMID:185194

  8. Natural chelating agents for radionuclide decorporation

    DOEpatents

    Premuzic, E.T.

    1985-06-11

    This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

  9. Objectives and Methods of Iron Chelation Therapy

    PubMed Central

    Hershko, C.; Abrahamov, A.; Konijn, A. M.; Breuer, W.; Cabantchik, I. Z.; Pootrakul, P.; Link, G.

    2003-01-01

    Recent developments in the understanding of the molecular control of iron homeostasis provided novel insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival. However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Within recent years more than one thousand candidate compounds have been screened in animal models. The most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and; bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance by decreasing the demand on tedious parenteral drug administration. Combined use of DFO

  10. Myelodysplastic Syndromes and Iron Chelation Therapy

    PubMed Central

    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

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

    PubMed

    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 < 0.05). However, materials still retained at least 76% iron chelating capacity. Additionally, the 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

  12. Iron chelation therapy in thalassemia syndromes.

    PubMed

    Cianciulli, Paolo

    2009-12-29

    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.

  13. Iron Chelation Therapy in Thalassemia Syndromes

    PubMed Central

    Cianciulli, Paolo

    2009-01-01

    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. PMID:21415999

  14. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

    Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

    1998-01-01

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

  15. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

    Smart, N.G.; Wai, C.M.; Lin, Y.; Kwang, Y.H.

    1998-11-24

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO{sub 2}, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO{sub 2} and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process. 1 fig.

  16. Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin

    PubMed Central

    Yalcintepe, Leman; Halis, Emre

    2016-01-01

    Increased intracellular iron levels can both promote cell proliferation and death, as such; iron has a “two-sided effect” in the delicate balance of human health. Though the role of iron in the development of cancer remains unclear, investigations of iron chelators as anti-tumor agents have revealed promising results. Here, we investigated the influence of iron and desferrioxamine (DFO), the iron chelating agent on intracellular calcium in a human leukemia cell line, K562. Iron uptake is associated with increased reactive oxygen species (ROS) generation. Therefore, we showed that iron also caused dose-dependent ROS generation in K562 cells. The measurement of intracellular calcium was determined using Furo-2 with a fluorescence spectrophotometer. The iron delivery process to the cytoplasmic iron pool was examined by monitoring the fluorescence of cells loaded with calcein-acetoxymethyl. Our data showed that iron increased intracellular calcium, and this response was 8 times higher when cells were incubated with DFO. K562 cells with DFO caused a 3.5 times increase of intracellular calcium in the presence of doxorubicin (DOX). In conclusion, DFO induces intracellular calcium and increases their sensitivity to DOX, a chemotherapeutic agent. PMID:26773173

  17. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

    2013-09-01

    Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

  18. Effect of trace iron levels and iron withdrawal by chelation on the growth of Candida albicans and Candida vini.

    PubMed

    Holbein, Bruce E; Mira de Orduña, Ramón

    2010-06-01

    The iron requirements of the opportunistic pathogenic yeast, Candida albicans, and the related nonpathogenic spoilage yeast Candida vini were investigated along with their responses to various exogenous iron chelators. The influence of iron as well as the exogenous chelating agents lactoferrin, EDTA, deferiprone, desferrioxamine, bathophenanthroline sulphonate and a novel carried chelator with a hydroxypyridinone-like Fe-ligand functionality, DIBI, on fungal growth was studied in a chemically defined medium deferrated to trace iron levels (<1.2 microg L(-1) or 0.02 microM of Fe). Candida albicans competed better at low iron levels compared with C. vini, which was also more susceptible to most added chelators. Candida albicans was resistant to lactoferrin at physiologically relevant concentrations, but was inhibited by low concentrations of DIBI. Candida vini was sensitive to lactoferrin as well as to DIBI, whose inhibitory activity was shown to be Fe reversible. The pathogenic potential of C. albicans and the nonpathogenic nature of C. vini were consistent with their differing abilities to grow under iron-limiting conditions and in the presence of exogenous iron chelators. Both yeasts could be controlled by appropriately strong chelators. This work provides the first evidence of the iron requirements of the spoilage organism C. vini and its response to exogenous chelators. Efficient iron withdrawal has the potential to provide the basis for new fungal growth control strategies.

  19. Iron chelators in medicinal applications - chemical equilibrium considerations in pharmaceutical activity.

    PubMed

    Manning, Thomas; Kean, Greg; Thomas, Jessica; Thomas, Khaleh; Corbitt, Michael; Gosnell, Donna; Ware, Ronald; Fulp, Sonya; Jarrard, Joey; Phillips, Dennis

    2009-01-01

    Iron chelators are being examined as a potential class of pharmaceutical agents to battle different types of cancer as well as iron overload diseases. In recent studies, iron binding species such as desferrioxamine, triapine, tachpyridine, Dp44Mt, and PIH have been tested in cell line tests and clinical trials. Using published chemical equilibrium values (stability constants, equilibrium constants), it is argued that an iron chelator cannot competitively remove iron from a heme-containing biomolecule (i.e. hemoglobin (Hb), myoglobin) causing a cancerous cell to die. This type of reaction (DFO(aq) + [Fe(2+,3+)-Hb] --> [Fe(2+,3+)-DFO] + Hb) has been proposed in a number of published studies using circumstantial evidence. It is argued that iron chelators can potentially interact with iron from ferritin or iron that has precipitated or flocculated as oxyhydroxide under physiological pH's. It is argued that chelators can interfere with various physiological processes by binding cations such as Ca(2+), Zn(2+) or K(+). A number of siderophores and natural products that have the ability to bind Fe(3+)/Fe(2+) as well as other cations are discussed in terms of their potential pharmaceutical activity as chelators. Chemical equilibria between cations and pharmaceutical agents, which are rarely quantitated in explaining medicinal mechanisms, are used to show that chelators can bind and remove iron and other cations from physiologically important systems required for cell survival and propagation.

  20. Metal regeneration of iron chelates in nitric oxide scrubbing

    DOEpatents

    Chang, Shih-Ger; Littlejohn, David; Shi, Yao

    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.degree. and 90.degree. 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.

  1. Metal regeneration of iron chelates in nitric oxide scrubbing

    DOEpatents

    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.

  2. Synthetic and natural iron chelators: therapeutic potential and clinical use

    PubMed Central

    Hatcher, Heather C; Singh, Ravi N; Torti, Frank M; Torti, Suzy V

    2013-01-01

    Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade®) and deferiprone (Ferriprox®), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry. PMID:21425984

  3. Iron release and uptake by plant ferritin: effects of pH, reduction and chelation.

    PubMed Central

    Laulhere, J P; Briat, J F

    1993-01-01

    Ferritins are iron-storage proteins that accumulate in plastids during seed formation, and also in leaves during senescence or iron overload. Iron release from ferritins occurs during growth of seedlings and greening of plastids. Depending on the concentration of the reducing agent ascorbate, either an overall iron release or uptake by ferritins from iron(III) citrate may occur. We have designed methods to measure these simultaneous and independent uptake and release fluxes. Each individual step of the exchange was studied using different iron chelates and an excess of ligand. It is shown that: (i) the chelated form of iron, and not ionic Fe3+, is the substrate for iron reduction, which controls the subsequent uptake by ferritin; (ii) iron uptake by ferritins is faster at pH 8.4 than at pH 7 or 6 and is inhibited by an excess of strongly binding free ligands; and (iii) strongly binding free ligands are inhibitory during iron release by ascorbate. When reactions are allowed to proceed simultaneously, the iron chelating power is shown to be a key factor in the overall exchange. The interactions of iron chelating power, reducing capacity and pH are discussed with regard to their influence on the biochemical mobilization of iron. Images Figure 1 Figure 6 Figure 7 PMID:8457196

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

    PubMed Central

    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

  5. Iron chelators target both proliferating and quiescent cancer cells

    PubMed Central

    Fryknäs, Mårten; Zhang, Xiaonan; Bremberg, Ulf; Senkowski, Wojciech; Olofsson, Maria Hägg; Brandt, Peter; Persson, Ingmar; D’Arcy, Padraig; Gullbo, Joachim; Nygren, Peter; Schughart, Leoni Kunz; Linder, Stig; Larsson, Rolf

    2016-01-01

    Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells. PMID:27924826

  6. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    SciTech Connect

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-10-25

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics.

  7. A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation.

    PubMed

    Charkoudian, Louise K; Pham, David M; Franz, Katherine J

    2006-09-27

    The synthesis and structural characterization of a new pro-chelating agent, isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide (BSIH), are presented. BSIH only weakly interacts with iron unless hydrogen peroxide (H2O2) is present to remove the boronic ester protecting group to reveal a phenol that is a key metal-binding group of tridentate salicylaldehyde isonicotinoyl hydrazone (SIH). BSIH prevents deoxyribose degradation caused by hydroxyl radicals that are generated from H2O2 and redox-active iron by sequestering Fe3+ and preventing iron-promoted hydroxyl radical formation. The rate-determining step for iron sequestration is conversion of BSIH to SIH, followed by rapid Fe3+ complexation. The pro-chelate approach of BSIH represents a promising strategy for chelating a specific pool of detrimental metal ions without disturbing healthy metal ion distribution.

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

    PubMed

    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.

  9. Effect of iron chelators on placental uptake and transfer of iron in rat

    SciTech Connect

    Wong, C.T.; McArdle, H.J.; Morgan, E.H.

    1987-05-01

    The uptake of radiolabeled transferrin and iron by the rat placenta has been studied using two approaches. The first involved injection of a ferrous or ferric iron chelator followed by injection of label. Neither chelator decreased the amount of labelled transferrin in the placenta after 2-h incubation and only bipyridine, a ferrous iron chelator, inhibited iron transport to the fetus. Deferoxamine (DFO), a ferric iron chelator, had no effect on iron transport to the fetus but reduced iron uptake by the liver. Both bipyridine and DFO increased iron excretion into the gut and by the urinary tract to the same degree into the gut, but there was a 10-fold greater urinary excretion with bipyridine than with DFO. Injection of iron attached to the chelators showed that neither bipyridine nor DFO could donate iron to the fetus as efficiently as transferrin. The mechanism involved was further investigated by studying the effect of the chelators on uptake of transferrin-bound iron by placental cells in culture. DFO inhibited iron accumulation more effectively than bipyridine in the cultured cells. The effect was not due to a decrease in the cycling time of the receptor. The results can be explained if the iron is released from the transferrin in intracellular vesicles in the ferrous form, where it may be chelated by bipyridine and prevented from passing to the fetus or converted to the ferric form once it is inside the cell matrix.

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

    PubMed

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    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.

  11. Desferrithiocin: A Search for Clinically Effective Iron Chelators

    PubMed Central

    2015-01-01

    The successful search for orally active iron chelators to treat transfusional iron-overload diseases, e.g., thalassemia, is overviewed. The critical role of iron in nature as a redox engine is first described, as well as how primitive life forms and humans manage the metal. The problems that derive when iron homeostasis in humans is disrupted and the mechanism of the ensuing damage, uncontrolled Fenton chemistry, are discussed. The solution to the problem, chelator-mediated iron removal, is clear. Design options for the assembly of ligands that sequester and decorporate iron are reviewed, along with the shortcomings of the currently available therapeutics. The rationale for choosing desferrithiocin, a natural product iron chelator (a siderophore), as a platform for structure–activity relationship studies in the search for an orally active iron chelator is thoroughly developed. The study provides an excellent example of how to systematically reengineer a pharmacophore in order to overcome toxicological problems while maintaining iron clearing efficacy and has led to three ligands being evaluated in human clinical trials. PMID:25207964

  12. Oxidation-Induced Degradable Nanogels for Iron Chelation

    NASA Astrophysics Data System (ADS)

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-02-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells.

  13. Oxidation-Induced Degradable Nanogels for Iron Chelation

    PubMed Central

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-01-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

  14. An Evaluation of the Chelating Agent EDDS for Floriculture Crop Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) ligands (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 plants. When complexed with Fe, EDTA and...

  15. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, Kenneth; Xu, Jide

    1999-01-01

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

  16. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, K.; Xu, J.

    1999-04-06

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

  17. Chelating agents used for plutonium and uranium removal in radiation emergency medicine.

    PubMed

    Fukuda, Satoshi

    2005-01-01

    The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.

  18. Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with Consequences on Tumor Progression

    PubMed Central

    Mertens, Christina; Akam, Eman Abureida; Rehwald, Claudia; Brüne, Bernhard; Tomat, Elisa

    2016-01-01

    A growing body of evidence suggests that macrophage polarization dictates the expression of iron-regulated genes. Polarization towards iron sequestration depletes the microenvironment, whereby extracellular pathogen growth is limited and inflammation is fostered. In contrast, iron release contributes to cell proliferation, which is important for tissue regeneration. Moreover, macrophages constitute a major component of the infiltrates in most solid tumors. Considering the pivotal role of macrophages for iron homeostasis and their presence in association with poor clinical prognosis in tumors, we approached the possibility to target macrophages with intracellular iron chelators. Analyzing the expression of iron-regulated genes at mRNA and protein level in primary human macrophages, we found that the iron-release phenotype is a characteristic of polarized macrophages that, in turn, stimulate tumor cell growth and progression. The application of the intracellular iron chelator (TC3-S)2 shifted the macrophage phenotype from iron release towards sequestration, as determined by the iron-gene profile and atomic absorption spectroscopy (AAS). Moreover, whereas the addition of macrophage supernatants to tumor cells induced tumor growth and metastatic behavior, the supernatant of chelator-treated macrophages reversed this effect. Iron chelators demonstrated potent anti-neoplastic properties in a number of cancers, both in cell culture and in clinical trials. Our results suggest that iron chelation could affect not only cancer cells but also the tumor microenvironment by altering the iron-release phenotype of tumor-associated macrophages (TAMs). The study of iron chelators in conjunction with the effect of TAMs on tumor growth could lead to an improved understanding of the role of iron in cancer biology and to novel therapeutic avenues for iron chelation approaches. PMID:27806101

  19. Targeting Chelatable Iron as a Therapeutic Modality in Parkinson's Disease

    PubMed Central

    Moreau, Caroline; Devedjian, Jean Christophe; Kluza, Jérome; Petrault, Maud; Laloux, Charlotte; Jonneaux, Aurélie; Ryckewaert, Gilles; Garçon, Guillaume; Rouaix, Nathalie; Duhamel, Alain; Jissendi, Patrice; Dujardin, Kathy; Auger, Florent; Ravasi, Laura; Hopes, Lucie; Grolez, Guillaume; Firdaus, Wance; Sablonnière, Bernard; Strubi-Vuillaume, Isabelle; Zahr, Noel; Destée, Alain; Corvol, Jean-Christophe; Pöltl, Dominik; Leist, Marcel; Rose, Christian; Defebvre, Luc; Marchetti, Philippe; Cabantchik, Z. Ioav; Bordet, Régis

    2014-01-01

    Abstract Aims: The pathophysiological role of iron in Parkinson's disease (PD) was assessed by a chelation strategy aimed at reducing oxidative damage associated with regional iron deposition without affecting circulating metals. Translational cell and animal models provided concept proofs and a delayed-start (DS) treatment paradigm, the basis for preliminary clinical assessments. Results: For translational studies, we assessed the effect of oxidative insults in mice systemically prechelated with deferiprone (DFP) by following motor functions, striatal dopamine (HPLC and MRI-PET), and brain iron deposition (relaxation-R2*-MRI) aided by spectroscopic measurements of neuronal labile iron (with fluorescence-sensitive iron sensors) and oxidative damage by markers of protein, lipid, and DNA modification. DFP significantly reduced labile iron and biological damage in oxidation-stressed cells and animals, improving motor functions while raising striatal dopamine. For a pilot, double-blind, placebo-controlled randomized clinical trial, early-stage Parkinson's patients on stabilized dopamine regimens enrolled in a 12-month single-center study with DFP (30 mg/kg/day). Based on a 6-month DS paradigm, early-start patients (n=19) compared to DS patients (n=18) (37/40 completed) responded significantly earlier and sustainably to treatment in both substantia nigra iron deposits (R2* MRI) and Unified Parkinson's Disease Rating Scale motor indicators of disease progression (p<0.03 and p<0.04, respectively). Apart from three rapidly resolved neutropenia cases, safety was maintained throughout the trial. Innovation: A moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality for PD. Conclusions: The therapeutic features of a chelation modality established in translational models and in pilot clinical trials warrant comprehensive evaluation of symptomatic and/or disease-modifying potential of chelation in PD. Antioxid

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

    PubMed

    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.

  1. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, K.N.; Xu, J.

    1997-04-29

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

  2. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, Kenneth N.; Xu, Jide

    1997-01-01

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

    PubMed

    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.

  5. Interaction of chelating agents with cadmium in mice and rats.

    PubMed Central

    Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

    1984-01-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

  6. Interaction of chelating agents with cadmium in mice and rats

    SciTech Connect

    Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

    1984-03-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl/sub 2/ and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl/sub 2/ was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatement of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl/sub 2/ and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of /sup 115m/Cd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes.

  7. 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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

    Aguirre, Pabla; Mena, Natalia P; Carrasco, Carlos M; Muñoz, Yorka; Pérez-Henríquez, Patricio; Morales, Rodrigo A; Cassels, Bruce K; Méndez-Gálvez, Carolina; García-Beltrán, Olimpo; González-Billault, Christian; Núñez, Marco T

    2015-01-01

    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.

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

    PubMed Central

    Aguirre, Pabla; Mena, Natalia P.; Carrasco, Carlos M.; Muñoz, Yorka; Pérez-Henríquez, Patricio; Morales, Rodrigo A.; Cassels, Bruce K.; Méndez-Gálvez, Carolina; García-Beltrán, Olimpo; González-Billault, Christian; Núñez, Marco T.

    2015-01-01

    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. PMID:26658949

  10. River-derived humic substances as iron chelators in seawater

    PubMed Central

    Krachler, Regina; Krachler, Rudolf F.; Wallner, Gabriele; Hann, Stephan; Laux, Monika; Cervantes Recalde, Maria F.; Jirsa, Franz; Neubauer, Elisabeth; von der Kammer, Frank; Hofmann, Thilo; Keppler, Bernhard K.

    2015-01-01

    The speciation of iron(III) in oxic seawater is dominated by its hydrolysis and sedimentation of insoluble iron(III)-oxyhydroxide. As a consequence, many oceanic areas have very low iron levels in surface seawater which leads to iron deficiency since phytoplankton require iron as a micronutrient in order to grow. Fortunately, iron solubility is not truly as low as Fe(III) solubility measurements in inorganic seawater would suggest, since oceanic waters contain organic molecules which tend to bind the iron and keep it in solution. Various iron-binding organic ligands which combine to stabilize dissolved iron have been detected and thoroughly investigated in recent years. However, the role of iron-binding ligands from terrestrial sources remains poorly constrained. Blackwater rivers supply large amounts of natural organic material (NOM) to the ocean. This NOM (which consists mainly of vascular plant-derived humic substances) is able to greatly enhance iron bioavailability in estuaries and coastal regions, however, breakdown processes lead to a rapid decrease of river-derived NOM concentrations with increasing distance from land. It has therefore been argued that the influence of river-derived NOM on iron biogeochemistry in offshore seawater does not seem to be significant. Here we used a standard method based on 59Fe as a radiotracer to study the solubility of Fe(III)-oxyhydroxide in seawater in the presence of riverine NOM. We aimed to address the question how effective is freshwater NOM as an iron chelator under open ocean conditions where the concentration of land-derived organic material is about 3 orders of magnitude smaller than in coastal regions, and does this iron chelating ability vary between NOM from different sources and between different size fractions of the river-borne NOM. Our results show that the investigated NOM fractions were able to substantially enhance Fe(III)-oxyhydroxide solubility in seawater at concentrations of the NOM ≥ 5

  11. ATMP-stabilized iron nanoparticles: chelator-controlled nanoparticle synthesis

    NASA Astrophysics Data System (ADS)

    Greenlee, Lauren F.; Rentz, Nikki S.

    2014-11-01

    In this study, we characterize iron nanoparticles synthesized in water in the presence of a phosphonate chelator, amino tris(methylene phosphonic acid) (ATMP) for a range of molar ratios of ATMP to iron. An increase in the molar ratio from 0.05 to 0.8 decreases nanoparticle size from approximately 150 nm to less than 10 nm. Zeta potential measurements were used to evaluate colloidal stability. Zeta potential values varied as a function of pH, and zeta potential values decreased with increasing pH. At lower molar ratios of ATMP to iron, the zeta potential varied between 15 and -40 mV, passing through an isoelectric point at pH 7.5. At higher ratios, the zeta potential was negative across the measured pH range of 2-12 and varied from -2 to -55 mV. Diffraction analysis indicates that ATMP-stabilized iron nanoparticles may have a nano-crystalline structure, potentially with regions of amorphous iron. Characterization results of ATMP-stabilized iron nanoparticles are compared to results obtained for carboxymethyl cellulose (CMC)-stabilized iron nanoparticles. CMC stabilization caused similar peak broadening in diffraction spectra as for ATMP, suggesting similar nano-crystalline/amorphous structure; however, an increase in the molar ratio of CMC to iron did not cause the same reduction in nanoparticle size as was observed for ATMP-stabilized iron nanoparticles.

  12. Proteomic profiling reveals that collismycin A is an iron chelator

    PubMed Central

    Kawatani, Makoto; Muroi, Makoto; Wada, Akira; Inoue, Gyo; Futamura, Yushi; Aono, Harumi; Shimizu, Kenshirou; Shimizu, Takeshi; Igarashi, Yasuhiro; Takahashi-Ando, Naoko; Osada, Hiroyuki

    2016-01-01

    Collismycin A (CMA), a microbial product, has anti-proliferative activity against cancer cells, but the mechanism of its action remains unknown. Here, we report the identification of the molecular target of CMA by ChemProteoBase, a proteome-based approach for drug target identification. ChemProteoBase profiling showed that CMA is closely clustered with di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, an iron chelator. CMA bound to both Fe(II) and Fe(III) ions and formed a 2:1 chelator-iron complex with a redox-inactive center. CMA-induced cell growth inhibition was completely canceled by Fe(II) and Fe(III) ions, but not by other metal ions such as Zn(II) or Cu(II). Proteomic and transcriptomic analyses showed that CMA affects the glycolytic pathway due to the accumulation of HIF-1α. These results suggest that CMA acts as a specific iron chelator, leading to the inhibition of cancer cell growth. PMID:27922079

  13. Experimental animal model to study iron overload and iron chelation and review of other such models.

    PubMed

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2015-10-01

    The disorders of iron overload due to primary or secondary cause are one of the important human diseases leading to high mortality if untreated. To understand this, an animal model has been extensively studied. The source of iron administered to the mode of iron administration that can mimic the iron overload in humans has been studied. A safe and orally active iron chelator is still needed as many of the existing compounds have different types of complications and toxicity associated. Hence having a simple animal model which can be availed quickly and can be used to study various compounds for its iron chelating activity would likely to have immense utility for pharmacological studies. In this review we have shown how, using a simple procedure, a large number of small iron overloaded animals can be produced easily for various studies.

  14. Influence of polycarboxylic acid chelating agents on the kinetics of the dissolution of metal oxides

    SciTech Connect

    Dyatlova, N.M.; Gorichev, I.G.; Dukhanin, V.S.; Malov, L.V.

    1986-11-01

    The factors influencing the rate of dissolution of metal oxides in aqueous solutions of acids in the presence of polycarboxylic acid chelating agents and other complexing agents have been quantitatively compared in this review, and the decisive role of the gradient of protons and electrons in the realization of this process has been revealed. The main hypotheses of the proposed conceptions of the electron-proton theory for the dissolution of metal oxides have been stated: 1) The rate-limiting step is charge transfer (first hypothesis); 2) The rate limiting step is the desorption of the dissolution products (second hypothesis). The applicability of the proposed electron-proton theory to the theoretical substantiation of all the experimentally observed kinetic features of the influence of various factors has been demonstrated. Practical recommendations for the effective utilization of the chelating agents considered for removing iron oxide surface deposits have been given.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

    Alcain, F J; Löw, H; Crane, F L

    1994-08-16

    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 90 min. Growth factor stimulation of DNA synthesis and electron transport are restored by addition of di- or trivalent iron to the cells in the form of ferric ammonium citrate, ferrous ammonium sulfate, or diferric transferrin. The effect with BPS differs from the inhibition of growth by hydroxyurea, which acts on the ribonucleotide reductase, or diethylenetriaminepentaacetic acid, which is another impermeable chelating agent, in that these agents inhibit growth in 10% fetal calf serum. The BPS effect is consistent with removal of iron from a site on the cell surface that controls DNA synthesis.

  18. Iron Reverses Impermeable Chelator Inhibition of DNA Synthesis in CCl39 Cells

    NASA Astrophysics Data System (ADS)

    Alcain, Francisco J.; Low, Hans; Crane, Frederick L.

    1994-08-01

    Treatment of Chinese hamster lung fibro-blasts (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 90 min. Growth factor stimulation of DNA synthesis and electron transport are restored by addition of di- or trivalent iron to the cells in the form of ferric ammonium citrate, ferrous ammonium sulfate, or diferric transferrin. The effect with BPS differs from the inhibition of growth by hydroxyurea, which acts on the ribonucleotide reductase, or diethylenetriaminepentaacetic acid, which is another impermeable chelating agent, in that these agents inhibit growth in 10% fetal calf serum. The BPS effect is consistent with removal of iron from a site on the cell surface that controls DNA synthesis.

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

    PubMed

    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

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

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    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

  1. Method for preparing radionuclide-labeled chelating agent-ligand complexes

    DOEpatents

    Meares, Claude F.; Li, Min; DeNardo, Sally J.

    1999-01-01

    Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

  2. Archetypes for actinide-specific chelating agents

    SciTech Connect

    Smith, W.L.

    1980-01-01

    The complexes of uranium and thorium with monomeric hydroxamic acids can serve as archetypes for an optimized macrochelate designed for tetravalent actinides. The eight-coordinate complexes, Th(i-PrN(O)C(O)R)/sub 4/, where R = tert-butyl or R = neopentyl, have been synthesized and their structures have been determined by x-ray diffraction. The bulky alkyl substituents impart remarkable volatility and hydrocarbon solubility to these complexes, and the steric interactions of these substituents largely determine the structures. When R = tert-butyl, the substituents occupy the corners of a tetrahedron and force the complex into a distorted cubic geometry with crystallographic S/sub 4/ symmetry. Insertion of a methylene group between the carbonyl carbon and the tert-butyl group relaxes the steric requirements, and the coordination polyhedron of the neopentyl derivative is close to the mmmm isomer of the trigonal-faced dodecahedron. Uranium tetrachloride was quantitatively oxidized via an oxygen transfer reaction with two equivalents of N-phenylbenzohydroxamic acid anion (PBHA) in tetrahydrofuran (THF) to form UO/sub 2/ Cl(PBHA)(THF)/sub 2/ and benzanilide. The structure of the uranyl complex has been determined from x-ray diffraction data; the linear uranyl ion is surrounded by a planar pentagonal array composed of two hydroxamate oxygen atoms, a chloride ion and two THF oxygens, such that the chloride ion is opposite the hydroxamate group. That the THF and phenyl rings are twisted from this equatorial plane limits the molecular geometry to that of the C/sub 1/ point group. Some aspects of the chemistry of hydroxamic acids and of their incorporation into molecules that may serve as precursors of tetravalent actinide specific sequestering agents have also been investigated.

  3. Mercury removal in utility wet scrubber using a chelating agent

    DOEpatents

    Amrhein, Gerald T.

    2001-01-01

    A method for capturing and reducing the mercury content of an industrial flue gas such as that produced in the combustion of a fossil fuel or solid waste adds a chelating agent, such as ethylenediaminetetraacetic acid (EDTA) or other similar compounds like HEDTA, DTPA and/or NTA, to the flue gas being scrubbed in a wet scrubber used in the industrial process. The chelating agent prevents the reduction of oxidized mercury to elemental mercury, thereby increasing the mercury removal efficiency of the wet scrubber. Exemplary tests on inlet and outlet mercury concentration in an industrial flue gas were performed without and with EDTA addition. Without EDTA, mercury removal totaled 42%. With EDTA, mercury removal increased to 71%. The invention may be readily adapted to known wet scrubber systems and it specifically provides for the removal of unwanted mercury both by supplying S.sup.2- ions to convert Hg.sup.2+ ions into mercuric sulfide (HgS) and by supplying a chelating agent to sequester other ions, including but not limited to Fe.sup.2+ ions, which could otherwise induce the unwanted reduction of Hg.sup.2+ to the form, Hg.sup.0.

  4. Antimalarial action of hydroxamate-based iron chelators and potentiation of desferrioxamine action by reversed siderophores.

    PubMed Central

    Golenser, J; Tsafack, A; Amichai, Y; Libman, J; Shanzer, A; Cabantchik, Z I

    1995-01-01

    Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, and degree of reversibility of effects. This work explores the possibility of improving the antimalarial efficacy of these agents by using them in various combinations on in vitro cultures of P. falciparum. Growth assessment was based both on total nucleic acid synthesis and on parasitemia. The results indicate that the synthetic reversed siderophore more than complements the antimalarial action of desferrioxamine when applied during either ring, trophozoite, or mixed stages. The combined drug effects were significantly higher than the additive effect of the individual drugs. Qualitatively similar results were obtained for both reversible effects and irreversible (i.e., sustained) effects. Following an 8-h window of exposure the combined drug treatment caused parasite growth arrest and prevented its recovery, even 3 days after the treatment. The fact that such a combination of iron chelators displays a wider action spectrum than either drug alone has implications for the design of chemotherapy regimens. PMID:7695330

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. Iron chelation therapy in myelodysplastic syndromes: where do we stand?

    PubMed Central

    Mitchell, Mhairi; Gore, Steven D; Zeidan, Amer M

    2014-01-01

    Anemia leading to transfusion dependency (TD) and iron overload (IO) is commonly observed in patients with myelodysplastic syndromes (MDS). In MDS, TD and IO have been retrospectively associated with inferior survival and worse clinical outcomes, including cardiac, hepatic and endocrine dysfunction, and, in some analyses, with leukemic progression and infectious complications. Although suggested by retrospective analyses, clear prospective documentation of the beneficial effects of iron chelation therapy (ICT) on organ function and survival in MDS patients with TD and IO is currently lacking. Consequently, the role of ICT in MDS patients with TD and IO remains a very controversial aspect in the management of MDS. In this review, the authors summarize the current knowledge regarding IO in MDS and the role of ICT. PMID:23991926

  7. Iron overload in thalassemia and related conditions: therapeutic goals and assessment of response to chelation therapies.

    PubMed

    Porter, John B; Shah, Farrukh T

    2010-12-01

    Transfusional iron loading inevitably results in hepatic iron accumulation, with variable extrahepatic distribution that is typically less pronounced in sickle cell disease than in thalassemia disorders. Iron chelation therapy has the goal of preventing iron-mediated tissue damage through controlling tissue iron levels, without incurring chelator-mediated toxicity. Historically, target levels for tissue iron control have been limited by the increased frequency of deferoxamine-mediated toxicity and low levels of iron loading. With newer chelation regimes, these limitations are less evident. The reporting of responses to chelation therapies has typically focused on average changes in serum ferritin in patient populations. This approach has three limitations. First, changes in serum ferritin may not reflect trends in iron balance equally in all patients or for all chelation regimens. Second, this provides no information about the proportion of patients likely respond. Third, this gives insufficient information about iron trends in tissues such as the heart. Monitoring of iron overload has advanced with the increasing use of MRI techniques to estimate iron balance (changes in liver iron concentration) and extrahepatic iron distribution (myocardial T2*). The term nonresponder has been increasingly used to describe individuals who fail to show a downward trend in one or more of these variables. Lack of a response of an individual may result from inadequate dosing, high transfusion requirement, poor treatment adherence, or unfavorable pharmacology of the chelation regime. This article scrutinizes evidence for response rates to deferoxamine, deferiprone (and combinations), and deferasirox.

  8. Chemistry and bifunctional chelating agents for binding (177)Lu.

    PubMed

    Parus, Józef L; Pawlak, Dariusz; Mikolajczak, Renata; Duatti, Adriano

    2015-01-01

    A short overview of fundamental chemistry of lutetium and of structural characteristics of lutetium coordination complexes, as relevant for understanding the properties of lutetium-177 radiopharmaceuticals, is presented. This includes basic concepts on lutetium electronic structure, lanthanide contraction, coordination geometries, behavior in aqueous solution and thermodynamic stability. An illustration of the structure and binding properties of the most important chelating agents for the Lu(3+) ion in aqueous solution is also reported with specific focus on coordination complexes formed with linear and macrocyclic polydentate amino-carboxylate donor ligands.

  9. Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy.

    PubMed

    Leitch, Heather A

    2007-12-01

    Until recently, little information on the benefits of iron chelation therapy (ICT) in patients with myelodysplastic syndrome (MDS) and iron overload was known. A recent retrospective study showed improved survival in transfusion-dependent patients with MDS (Low or Intermediate-1 risk IPSS) receiving ICT, compared with those not receiving ICT; median overall survival was not reached at 160 months versus 40 months, respectively. Significantly more patients receiving ICT survived to 4 years (80% versus 44%; p < 0.03), suggesting that MDS patients with iron overload might benefit from ICT. Prospective studies to confirm the benefit of ICT in MDS are warranted.

  10. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

    PubMed

    Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

    2014-08-07

    Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population.

  11. Effects of iron chelators, iron salts, and iron oxide nanoparticles on the proliferation and the iron content of oligodendroglial OLN-93 cells.

    PubMed

    Hohnholt, Michaela; Geppert, Mark; Dringen, Ralf

    2010-08-01

    The oligodendroglial cell line OLN-93 was used as model system to investigate the consequences of iron deprivation or iron excess on cell proliferation. Presence of ferric or ferrous iron chelators inhibited the proliferation of OLN-93 cells in a time and concentration dependent manner, while the application of a molar excess of ferric ammonium citrate (FAC) prevented the inhibition of proliferation by the chelator deferoxamine. Proliferation of OLN-93 cells was not affected by incubation with 300 microM iron that was applied in the form of FAC, FeCl(2), ferrous ammonium sulfate or iron oxide nanoparticles, although the cells efficiently accumulated iron during exposure to each of these iron sources. The highest specific iron content was observed for cells that were exposed to the nanoparticles. These data demonstrate that the proliferation of OLN-93 cells depends strongly on the availability of iron and that these cells efficiently accumulate iron from various extracellular iron sources.

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

    PubMed

    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.

  13. Chelation and determination of labile iron in primary hepatocytes by pyridinone fluorescent probes

    PubMed Central

    Ma, Yongmin; de Groot, Herbert; Liu, Zudong; Hider, Robert C.; Petrat, Frank

    2005-01-01

    A series of fluorescent iron chelators has been synthesized such that a fluorescent function is covalently linked to a 3-hydroxypyridin-4-one. In the present study, the fluorescent iron chelators were loaded into isolated rat hepatocytes. The intracellular fluorescence was not only quenched by an addition of a highly lipophilic 8-hydroxyquinoline–iron(III) complex but also was dequenched by the addition of an excess of the membrane-permeable iron chelator CP94 (1,2-diethyl-3-hydroxypyridin-4-one). The time course of uptake of iron and iron chelation in single, intact cells was recorded on-line by using digital fluorescence microscopy. Intracellular concentrations of various fluorescent iron chelators were determined by using a spectrofluorophotometer subsequent to lysis of probe-loaded cells and were found to depend on their partition coefficients; the more hydrophobic the compound, the higher the intracellular concentration. An ex situ calibration method was used to determine the chelatable iron pool of cultured rat hepatocytes. CP655 (7-diethylamino-N-[(5-hydroxy-6-methyl-4-oxo-1,4-dihydropyridin-3-yl)methyl]-N-methyl-2-oxo-2H-chromen-3-carboxamide), which is a moderately lipophilic fluorescent chelator, was found to be the most sensitive probe for monitoring chelatable iron, as determined by the intracellular fluorescence increase induced by the addition of CP94. The concentration of the intracellular chelatable iron pool in hepatocytes was determined by this probe to be 5.4±1.3 μM. PMID:16336208

  14. Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

    PubMed Central

    Kontoghiorghes, G J; Aldouri, M A; Hoffbrand, A V; Barr, J; Wonke, B; Kourouclaris, T; Sheppard, L

    1987-01-01

    The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective

  15. The Oral Iron Chelator Deferiprone Protects against Iron Overload–Induced Retinal Degeneration

    PubMed Central

    Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Grieco, Steven; Lee, Jennifer; Lyubarsky, Arkady; Pratico, Domenico; Connelly, John; Spino, Michael; Harris, Z. Leah

    2011-01-01

    Purpose. Iron-induced oxidative stress may exacerbate age-related macular degeneration (AMD). Ceruloplasmin/Hephaestin double-knockout (DKO) mice with age-dependent retinal iron accumulation and some features of AMD were used to test retinal protection by the oral iron chelator deferiprone (DFP). Methods. Cultured retinal pigment epithelial (ARPE-19) cells and mice were treated with DFP. Transferrin receptor mRNA (Tfrc), an indicator of iron levels, was quantified by qPCR. In mice, retinal oxidative stress was assessed by mass spectrometry, and degeneration by histology and electroretinography. Results. DFP at 60 μM decreased labile iron in ARPE-19 cells, increasing Tfrc and protecting 70% of cells against a lethal dose of H2O2. DFP 1 mg/mL in drinking water increased retinal Tfrc mRNA 2.7-fold after 11 days and also increased transferrin receptor protein. In DKOs, DFP over 8 months decreased retinal iron levels to 72% of untreated mice, diminished retinal oxidative stress to 70% of the untreated level, and markedly ameliorated retinal degeneration. DFP was not retina toxic in wild-type (WT) or DKO mice, as assessed by histology and electroretinography. Conclusions. Oral DFP was not toxic to the mouse retina. It diminished retinal iron levels and oxidative stress and protected DKO mice against iron overload–induced retinal degeneration. Further testing of DFP for retinal disease involving oxidative stress is warranted. PMID:21051716

  16. Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators.

    PubMed

    Weinreb, Orly; Mandel, Silvia; Youdim, Moussa B H; Amit, Tamar

    2013-09-01

    Brain iron accumulation has been implicated in a host of chronic neurological diseases, including Parkinson's disease (PD). The elevated iron levels observed in the substantia nigra of PD subjects have been suggested to incite the generation of reactive oxygen species and intracellular α-synuclein aggregation, terminating in the oxidative neuronal destruction of this brain area. Thus, elucidation of the molecular mechanisms involved in iron dysregulation and oxidative stress-induced neurodegeneration is a crucial step in deciphering PD pathology and in developing novel iron-complexing compounds aimed at restoring brain iron homeostasis and attenuating neurodegeneration. This review discusses the involvement of dysregulation of brain iron homeostasis in PD pathology, with an emphasis on the potential effectiveness of naturally occurring compounds and novel iron-chelating/antioxidant therapeutic hybrid molecules, exerting a spectrum of neuroprotective interrelated activities: antioxidant/monoamine oxidase inhibition, activation of the hypoxia-inducible factor (HIF)-1 signaling pathway, induction of HIF-1 target iron-regulatory and antioxidative genes, and inhibition of α-synuclein accumulation and aggregation.

  17. Inhibition of in vitro lymphoproliferation by three novel iron chelators of the pyridoxal and salicyl aldehyde hydrazone classes.

    PubMed

    van Reyk, D; Sarel, S; Hunt, N

    2000-08-15

    The capacity of three novel iron chelators, namely 1-[N-ethoxycarbonylmethylpyridoxylidenium]-2-[2'-pyridyl]hydrazine bromide (EPH), 1-[5'-bromosalicylidene]-2-[2"-pyridyl]hydrazine (BsPH), and 1-pyridoxylidene-2-[1'-phthalazyl]hydrazine dihydrochloride (PPhH), to inhibit the proliferation of mitogen-stimulated murine lymph node cells was examined in vitro. All three are of the aryl hydrazone class, the prototype of which is pyridoxal isonicotinoyl hydrazone. The chelators inhibited lymphoproliferation at low micromolar concentrations. EPH and PPhH had an inhibitory capacity comparable to that of desferrioxamine (IC(50): 3 and 2 microM, respectively), whereas BsPH was more potent (IC(50) < 1 microM). The inhibitory effects of the chelator were not due to cell cytotoxicity and could be abrogated by pretreating the chelator with iron. Time-course studies established a site of action for the chelators at the G(1)/S phase transition. These agents warrant further investigation for their potential as immunosuppressants.

  18. The Influence of Chelating Agents on the Kinetics of Calcite Dissolution.

    PubMed

    Fredd; Fogler

    1998-08-01

    The kinetics of calcite dissolution in the presence of calcium chelating agents was investigated over the pH range of 3.3-12 using a rotating disk apparatus. The results show that the rate of dissolution is increased significantly by the presence of chelating agents such as CDTA, DTPA, and EDTA. The rate of dissolution is influenced by the kinetics of the chelation reactions and varies considerably with pH and type of chelating agent. A surface chelation mechanism was introduced to describe the dissolution. The mechanism involves the adsorption of the chelating agent onto the calcite surface and follows Langmuir-Hinshelwood kinetics. The dissolution is different from conventional hydrogen ion attack in that the chelating agent attacks the calcium component of the lattice rather than the carbonate component. Therefore, the rate of dissolution is enhanced by the influence of hydrogen ion attack at low pH. In addition, the various ionic forms of the chelating agents react with the calcite surface at different rates depending on the number of hydrogen ions associated with the species. In general, the rate of dissolution increases with increasing protonation. The surface complexation mechanism was shown to describe the rate of calcite dissolution in the presence of chelating agents over the pH range of 4-12. Copyright 1998 Academic Press.

  19. Obligatory Reduction of Ferric Chelates in Iron Uptake by Soybeans

    PubMed Central

    Chaney, Rufus L.; Brown, John C.; Tiffin, Lee O.

    1972-01-01

    The contrasting Fe2+ and Fe3+ chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe3+-chelates. EDDHA binds Fe3+ strongly, but Fe2+ weakly; BPDS binds Fe2+ strongly but Fe3+ weakly. Addition of an excess of BPDS to nutrient solutions containing Fe3+-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)3]4− accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe3+-chelates appear to require reduction of Fe3+-chelate to Fe2+-chelate at the root, with Fe2+ being the principal form of Fe absorbed by soybean. PMID:16658143

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

    PubMed

    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.

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

    PubMed

    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: < 0.05). When ferrous sulfate and ferrochel were administered together or in different meals, absorption from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05). Polyphenols present in coffee and tea inhibited iron absorption in a dose-dependent manner. 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.

  2. Synthesis and characterization of dihexyldithiocarbamate as a chelating agent in extraction of gold(III)

    SciTech Connect

    Fatimah, Soja Siti; Bahti, Husein H.; Hastiawan, Iwan; Permanasari, Anna

    2016-02-08

    The use of dialkyldithiocarbamates as chelating agents of transition metals have been developing for decades. Many chelating agents have been synthesized and used in the extraction of the metals. Studies on particular aspects of extraction of the metals, such as the effect of increasing hydrophobicity of chelating agents on the effectiveness of the extraction, have been done. However, despite the many studies on the synthesis and applications of this type of chelating agents, interests in the aspect of molecular structure of the synthesized ligands and of their complexes, have been limited. This study aimed at synthesizing and characterizing dihexylthiocarbamate, and using the ligand for the extraction of gold III). Characterization of the ligand and of its metal complex were done by using elemental analysis, DTG, and spectroscopic methods to include NMR, ({sup 1}H, and {sup 13}C), FTIR, and MS-ESI. Data on the synthesis, characterization, and the application of the ligand as a chelating agent are presented.

  3. New synthetic approach and iron chelating studies of 1-alkyl-2-methyl-3-hydroxypyrid-4-ones.

    PubMed

    Kontoghiorghes, G J; Sheppard, L; Chambers, S

    1987-10-01

    The major diseases of iron metabolism are iron deficiency anaemia, which could be treated using Fe2+ or Fe3+ salt supplements, and iron overload, which could arise either from an increased gastrointestinal absorption of iron or from recurrent blood transfusions. While the former form of iron overload could be treated by phlebotomy the latter requires the use of a chelator. Desferrioxamine is the only clinically available chelator for the treatment of iron overload but its use worldwide is limited because it is expensive and orally inactive. Several alpha-ketohydroxy heteroaromatic chelators have been synthesised and tested for their iron binding properties at physiological pH. The synthetic route involves the benzylation of the hydroxyl group of maltol using benzyl chloride, the conversion of the benzylated maltol to the 1-alkyl benzylated pyridine derivative by introducing the corresponding alkylamine in alkaline conditions and the cleavage of the benzyl group in acid to form the 1-alkyl-2-methyl-3-hydroxypyrid-4-one. All the chelators are water soluble and stable at a wide range of pH, forming stable, water soluble, coloured iron complexes with a molar ratio of approximately 3 chelator: 1 iron at pH 7.4 and lower molar ratio of chelators to iron complexes at acidic pH. When the 1-methyl, 1-ethyl and 1-propyl, -2-methyl-3-hydroxypyrid-4-ones were mixed at pH 7.4 with transferrin, ferritin and haemosiderin substantial amounts of iron were released.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

    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. Role of lipid oxidation, chelating agents, and antioxidants in metallic flavor development in the oral cavity.

    PubMed

    Omür-Özbek, Pinar; Dietrich, Andrea M; Duncan, Susan E; Lee, YongWoo

    2012-03-07

    This study investigated the production of metallic flavor, which is a combination of taste and retronasal odor. Chemical reactions in the oral cavity and saliva of healthy subjects were investigated after ingesting iron and copper solutions above and near threshold levels. Significant increase in lipid oxidation (p < 0.001) occurred after metal ingestion, detected as TBARS values. Ferrous ion caused the greatest flavor sensation and lipid oxidation, followed by cupric and cuprous ions. Ferric ion did not cause metallic sensation. Occurrence of oxidation was supported by damage to salivary proteins, detected as protein-carbonyls, and by a significant increase of odorous lipid oxidation related aldehydes. Sensory evaluation demonstrated that antioxidants (vitamins E and C) minimally reduced metallic flavor but that chelating agents (EDTA and lactoferrin) removed the metallic flavor. The role of lipid oxidation is essential for the production of a metallic flavor from ingestion of ferrous, cupric, and cuprous ions.

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

    PubMed

    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.

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

    PubMed Central

    Makis, Alexandros; Chaliasos, Nikolaos; Alfantaki, Sapfo; Karagouni, Paraskevi; Siamopoulou, Antigone

    2013-01-01

    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, P < 0.001). 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. PMID:24294523

  8. Fate of labeled hydroxamates during iron transport from hydroxamate-ion chelates.

    PubMed

    Arceneaux, J E; Davis, W B; Downer, D N; Haydon, A H; Byers, B R

    1973-09-01

    The fate of the hydroxamic acid-iron transport cofactors during iron uptake from the (59)Fe(3+) chelates of the (3)H-labeled hydroxamates schizokinen and aerobactin was studied by assay of simultaneous incorporation of both (59)Fe(3+) and (3)H. In the schizokinen-producing organism Bacillus megaterium ATCC 19213 transport of (59)Fe(3+) from the (3)H-schizokinen-(59)Fe(3+) chelate at 37 C was accompanied by rapid uptake and release (within 2 min) of (3)H-schizokinen, although (3)H-schizokinen discharge was temperature-dependent and did not occur at 0 C. In the schizokinen-requiring strain B. megaterium SK11 similar release of (3)H-schizokinen occurred only at elevated concentrations of the double-labeled chelate; at lower chelate concentrations, (3)H-schizokinen remained cell-associated. Temperature-dependent uptake of deferri (iron-free) (3)H-schizokinen to levels equivalent to those incorporated from the chelate form was noted in strain SK11, but strain ATCC 19213 showed only temperature-independent binding of low concentrations of deferri (3)H-schizokinen. These results indicate an initial temperature-independent binding of the ferric hydroxamate which is followed rapidly by temperature-dependent transport of the chelate into the cell and an enzyme catalyzed separation of iron from the chelate. The resulting deferri hydroxamate is discharged from the cell only when a characteristic intracellular concentration of the hydroxamate is exceeded, which happens in the schizokinen-requiring strain only at elevated concentrations of the chelate. This strain also appears to draw the deferri hydroxamate into the cell by a temperature-dependent mechanism. The aerobactin-producing organism Aerobacter aerogenes 62-1 also demonstrated rapid initial uptake and temperature-dependent discharge of (3)H-aerobactin during iron transport from (3)H-aerobactin-(59)Fe(3+), suggesting a similar ferric hydroxamate transport system in this organism.

  9. Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

    DOEpatents

    Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

    2003-10-21

    There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

  10. Inhibitory activity of chelating agent against bacteria associated with poultry processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N, N’-disuccinic acid (EDDS) are chelating agents that can bind minerals that produce water hardness. By sequestering minerals in hard water, chelators reduce water hardness and increase the ability of cleansers to remove dirt and debris dur...

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

    PubMed Central

    Mosayebnia, Mona; Shafiee-Ardestani, Mehdi; Pasalar, Parvin; Mashayekhi, Mojgan; Amanlou, Massoud

    2014-01-01

    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. PMID:24554907

  12. The role of antioxidants and iron chelators in the treatment of oxidative stress in thalassemia.

    PubMed

    Fibach, Eitan; Rachmilewitz, Eliezer A

    2010-08-01

    On the basis of all the presented data, one can conclude that oxidative stress plays a major role in the pathophysiology of thalassemia and other congenital and acquired hemolytic anemias. Free extracellular (labile plasma iron, LPI) and intracellular (labile iron pool, LIP) iron species that have been identified in thalassemic blood cells are responsible for generation of oxidative stress by catalyzing formation of oxygen radicals over the antioxidant capacity of the cell. Consequently, there is a rationale for iron chelation to eliminate the free-iron species, which in this respect, act like antioxidants. In addition, antioxidants such as vitamin E and polyphenols are also capable of ameliorating increased oxidative stress parameters and, given together with iron chelators, may provide a substantial improvement in the pathophysiology of hemolytic anemias and particularly in thalassemia.

  13. Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Medicinal and Personal Care Products.

    ERIC Educational Resources Information Center

    Hart, J. Roger

    1984-01-01

    Discusses various ethylenediaminetetraacetate (EDTA)-type chelating agents found in ophthalmic products, personal care products, and disinfectants. Also discusses the properties and action of these EDTA agents. (JN)

  14. Role of pH in metal adsorption from aqueous solutions containing chelating agents on chitosan

    SciTech Connect

    Wu, F.C.; Tseng, R.L.; Juang, R.S.

    1999-01-01

    The role of pH in adsorption of Cu(II) from aqueous solutions containing chelating agents on chitosan was emphasized. Four chelating agents including ethylenediaminetetraacetic acid (EDTA), citric acid, tartaric acid, and sodium gluconate were used. It was shown that the adsorption ability of Cu(II) on chitosan from its chelated solutions varied significantly with pH variations. The competition between coordination of Cu(II) with unprotonated chitosan and electrostatic interaction of the Cu(II) chelates with protonated chitosan took place because of the change in solution pH during adsorption. The maximum adsorption capacity was obtained within each optimal pH range determined from titration curves of the chelated solutions. Coordination of Cu(II) with the unprotonated chitosan was found to dominate at pH below such an optimal pH value.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Inhibition of DNA synthesis in CCL 39 cells by impermeable iron chelators.

    PubMed

    Alcaín, F J; Löw, H; Crane, F L

    1997-02-01

    The synthesis of DNA in CCl 39 cells is inhibited by the presence of the Fe2+ chelator bathophenanthroline disulfonate (BPS) when growth is stimulated by thrombin EGF plus insulin, but not by fetal calf serum. The presence of transferrin and Fe3+ in fetal calf serum can be the basis for lack of BPS effect with serum. The impermeable Fe3+ chelator Tiron does not, by itself, inhibit growth factor induced DNA synthesis, but it induces together with BPS inhibition on fetal calf serum induced DNA synthesis. The combined effect of BPS and Tiron is similar to inhibition of DNA synthesis by impermeable polyvalent DTPA which can chelate both Fe2+ and Fe3+ but does not inhibit ribonucleotide reductase in intact cells. Ferrous iron that bind BPS can relieve the inhibition at stoichiometric concentration. Ferric iron also prevents the inhibition even though it does not bind BPS. BPS does not inhibit DNA synthesis in HeLa cells. BPS reacts with iron from CCl 39 cells but not from HeLa cells. Data show that iron available for impermeable external chelators is in the ferrous state, and that exogenous iron should be reduced before it reverses the inhibition.

  17. Prooxidant and antioxidant properties of salicylaldehyde isonicotinoyl hydrazone iron chelators in HepG2 cells

    PubMed Central

    Caro, Andres A.; Commissariat, Ava; Dunn, Caroline; Kim, Hyunjoo; García, Salvador Lorente; Smith, Allen; Strang, Harrison; Stuppy, Jake; Desrochers, Linda P.; Goodwin, Thomas E.

    2015-01-01

    Background Salicylaldehyde isonicotinoyl hydrazone (SIH) is an iron chelator of the aroylhydrazone class that displays antioxidant or prooxidant effects in different mammalian cell lines. Because the liver is the major site of iron storage, elucidating the effect of SIH on hepatic oxidative metabolism is critical for designing effective hepatic antioxidant therapies. Methods Hepatocyte-like HepG2 cells were exposed to SIH or to analogs showing greater stability, such as N′-[1-(2-Hydroxyphenyl)ethyliden]isonicotinoyl hydrazide (HAPI), or devoid of iron chelating properties, such as benzaldehyde isonicotinoyl hydrazone (BIH), and toxicity, oxidative stress and antioxidant (glutathione) metabolism were evaluated. Results Autoxidation of Fe2+ in vitro increased in the presence of SIH or HAPI (but not BIH), an effect partially blocked by Fe2+ chelation. Incubation of HepG2 cells with SIH or HAPI (but not BIH) was non-toxic and increased reactive oxygen species (ROS) levels, activated the transcription factor Nrf2, induced the catalytic subunit of γ-glutamate cysteine ligase (Gclc), and increased glutathione concentration. Fe2+ chelation decreased ROS and inhibited Nrf2 activation, and Nrf2 knock-down inhibited the induction of Gclc in the presence of HAPI. Inhibition of γ-glutamate cysteine ligase enzymatic activity inhibited the increase in glutathione caused by HAPI, and increased oxidative stress. Conclusions SIH iron chelators display both prooxidant (increasing the autoxidation rate of Fe2+) and antioxidant (activating Nrf2 signaling) effects. General significance Activation by SIH iron chelators of a hormetic antioxidant response contributes to its antioxidant properties and modulates the anti- and pro-oxidant balance. PMID:26275495

  18. Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric Thalassaemia Patients

    PubMed Central

    Hishikar, Rajesh; Khandwal, Onkar; Agarwal, Manju; Joshi, Usha; Halwai, Ajay; Maheshwari, Basant; Sheohare, Raka

    2017-01-01

    Introduction Thalassaemia Major patients require frequent blood transfusion leading to iron overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients with iron overload and its complications need safe and effective iron chelation therapy. Aim To assess the efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin level. Materials and Methods This is a prospective; observational study done in 45 multitransfused Thalassaemia Major Children receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh. DFX was given in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40 mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly intervals (four times during study period). The primary end point of the study was change in serum ferritin level after 12 months of DFX therapy. Results The mean serum ferritin before DFX therapy of all cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). Conclusion DFX monotherapy has a good safety profile and effectively chelates total body iron in Thalassaemia major patients. PMID:28384880

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

    PubMed Central

    Lee, Jehn-Chuan; Chiang, Kun-Chun; Feng, Tsui-Hsia; Chen, Yu-Jen; Chuang, Sung-Ting; Tsui, Ke-Hung; Chung, Li-Chuan; Juang, Horng-Heng

    2016-01-01

    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. PMID:27589737

  20. Iron uptake by Caco-2 cells from NaFeEDTA and FeSO4: Effects of ascorbic acid, pH, and a Fe(II) chelating agent.

    PubMed

    Zhu, Le; Glahn, Raymond P; Yeung, Chi Kong; Miller, Dennis D

    2006-10-04

    Sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA) has considerable promise as an iron fortificant because of its high bioavailability in foods containing iron absorption inhibitors. In this study, uptakes of iron from NaFeEDTA, FeSO4, and FeCl3 by Caco-2 cells were compared in the absence or presence of ascorbic acid (AA), an iron absorption enhancer; at selected pH levels; and in the absence or presence of an iron absorption inhibitor, bathophenanthroline disulfonic acid (BPDS). Ferritin formation in the cells was used as the indicator of iron uptake. Uptake from all three Fe sources was similar in the absence of AA. Adding AA at a 5:1 molar excess as compared to Fe increased uptake by 5.4-, 5.1-, and 2.8-fold for FeSO4, FeCl3, and NaFeEDTA, respectively. The smaller effect of AA on uptake from NaFeEDTA may be related to the higher solubility of NaFeEDTA and/or the strong binding affinity of EDTA for Fe3+, which may prevent AA and duodenal cytochrome b from effectively reducing EDTA-bound Fe. Uptake was inversely related to the pH of the media over a range of 5.8-7.2. Because uptake by DMT-1 is proton-coupled, the inverse relationship between pH and Fe uptake in all three iron sources suggests that they all follow the DMT-1 pathway into the cell. Adding BPDS to the media inhibited uptake from all three iron compounds equally. Because BPDS binds Fe2+ but not Fe3+ and because only Fe2+ is transported by DMT-1, the finding that BPDS inhibited uptake from NaFeEDTA suggests that at least some iron dissociates from EDTA and is reduced just as simple inorganic iron at the brush border membrane of the enterocyte. Taken together, these results suggest that uptake of iron from NaFeEDTA by intestinal enterocytes is regulated similarly to uptake from iron salts.

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

    PubMed

    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.

  2. Mössbauer spectroscopic study of iron-chelate trammels

    NASA Astrophysics Data System (ADS)

    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.

  3. Comparative effects of chelating agents on distribution, excretion, and renal toxicity of inorganic mercury in rats

    SciTech Connect

    Kojima, S.; Shimada, H.; Kiyozumi, M. )

    1989-06-01

    The effects of three chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate(NBG-DTC), 2,3-dimercaptopropanol(BAL), and D-penicillamine(D-PEN), on the distribution, excretion, and renal toxicity of inorganic mercury were compared in rats exposed to HgCl2. Rats were injected i.p. with 203HgCl2 (300 micrograms of Hg and 2 microCi of 203Hg/kg) and 30 min or 24 h later they were injected with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. BAL was the most effective for removal of mercury from the body at 30 min after mercury treatment. The extent of enhancing effect of the chelating agents for removal of mercury at 24 h after mercury was in the order NBG-DTC = BAL greater than D-PEN. The injection of BAL at 24 h after mercury treatment caused the redistribution of mercury to the heart and lung. NBG-DTC did not result in the redistribution of mercury to the heart, lung, and brain. Urinary excretion of protein and AST significantly increased 24-48 h after mercury treatment and decreased to the control values 72 h after mercury. The injection of the chelating agents at 30 min after mercury treatment significantly decreased the urinary excretion of protein and AST. In rats pretreated with mercury 24 h earlier, the chelating agents significantly decreased the urinary protein at 48 h after mercury treatment, but did not decrease the urinary AST. The results of this study indicate that the chelating agents are effective in removing mercury from the body, resulting in the protective effect against the mercury-induced renal damage.

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

    PubMed Central

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Sripetchwandee, Jirapas; Srichairatanakool, Somdet; Fucharoen, Suthat; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2016-01-01

    Background 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. Methods and Findings 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. Conclusions 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. PMID:27428732

  5. Chelating agents inhibit activity and prevent expression of streptococcal glucan-binding lectins.

    PubMed Central

    Lü-Lü; Singh, J S; Galperin, M Y; Drake, D; Taylor, K G; Doyle, R J

    1992-01-01

    Several of the cariogenic mutans streptococci produce cell wall-associated glucan-binding lectins (GBLs). The lectins bind alpha-1,6-linked glucans and have no affinity for other polysaccharides or anomeric linkages. When citrate or lactate was included in the growth medium, expression of the activities of the GBLs of Streptococcus cricetus and S. sobrinus was prevented. Furthermore, chelating agents, including citrate, lactate, EDTA, and acetylacetone, were able to reversibly inhibit glucan-induced aggregation of GBL+ streptococci. In addition, the chelating agents prevented sucrose-dependent streptococcal adhesion to glass surfaces and dispersed preformed adherent masses of the streptococci. Neither citrate nor other chelating agents modified the activities of glucosyltransferases. Expression of the lectin could only be achieved by the addition of manganous ion to the growth medium. Chloramphenicol and other metabolic inhibitors prevented synthesis of GBL in cells obtained from manganese-deficient medium and shifted to manganous ion-sufficient medium. The GBL may be a manganoprotein, the manganese of which may be perturbed, but not removed, by chelating agents. During synthesis of the GBL, manganous ion may be required in order for the protein to achieve an active conformation. Citrate or other chelating agents may have promise as anticaries agents. Images PMID:1500189

  6. Iron chelators increase the resistance of Ataxia telangeictasia cells to oxidative stress.

    PubMed

    Shackelford, Rodney E; Manuszak, Ryan P; Johnson, Cybele D; Hellrung, Daniel J; Link, Charles J; Wang, Suming

    2004-10-05

    Ataxia telangeictasia (A-T) is an autosomal recessive disorder characterized by immune dysfunction, genomic instability, chronic oxidative damage, and increased cancer incidence. Previously, desferal was found to increase the resistance of A-T, but not normal cells to exogenous oxidative stress in the colony forming-efficiency assay, suggesting that iron metabolism is dysregulated in A-T. Since desferal both chelates iron and modulates gene expression, we tested the effects of apoferritin and the iron chelating flavonoid quercetin on A-T cell colony-forming ability. We demonstrate that apoferritin and quercetin increase the ability of A-T cells to form colonies. We also show that labile iron levels are significantly elevated in Atm-deficient mouse sera compared to syngeniec wild type mice. Our findings support a role for labile iron acting as a Fenton catalyst in A-T, contributing to the chronic oxidative stress seen in this disease. Our findings further suggest that iron chelators might promote the survival of A-T cells and hence, individuals with A-T.

  7. (Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents)

    SciTech Connect

    Not Available

    1991-01-01

    Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

  8. [Bifunctional chelates of Rh-105, Au-199, and other metallic radionuclides as potential radiotherapeutic agents

    SciTech Connect

    Not Available

    1991-12-31

    Progress during this period is reported under the following headings: Diethylenetriamine based and related bifunctional chelating agents and their complexation with Rh-105, Au-198, Pd-109, cu-67, In-111, and Co-57; studies of Pd-109, Rh-105 and Tc-99m with bifunctional chelates based on phenylenediamine; establishment of an appropriate protein assay method for conjugated proteins; studies of new bifunctional Bi, Tri and tetradentate amine oxime ligands with Rh-105; IgG and antibody B72.3 conjugation studies by HPLC Techniques with bifunctional metal chelates; and progress on ligand systems for Au(III).

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

    PubMed Central

    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

  10. Specific sequestering agents for iron and the actinides

    SciTech Connect

    Raymond, K.N.

    1983-06-01

    The transuranium actinide ions represent one unique environmental hazard associated with the waste of the nuclear power industry. A major component associated with that waste and a potential hazard is plutonium. The synthesis of metal-ion-specific complexing agents for ions such as Pu(IV) potentially represents a powerful new approach to many of the problems posed by waste treatment. This document is a progress report of a rational approach to the synthesis of such chelating agents based on the similarities of Pu(IV) and Fe(III), the structures of naturally-occurring complexing agents which are highly specific for Fe(III), and the incorporation of the same kinds of ligating groups present in the iron complexes to make octadentate complexes highly specific for plutonium. Both thermodynamic and animal test results indicate that a relatively high degree of success has already been achieved in this aim.

  11. Ferrous iron chelating property of low-molecular weight succinoglycans isolated from Sinorhizobium meliloti.

    PubMed

    Cho, Eunae; Choi, Jae Min; Kim, Hwanhee; Tahir, Muhammad Nazir; Choi, Youngjin; Jung, Seunho

    2013-04-01

    Iron is an essential nutrient for nitrogen-fixing legume root nodules, and the chelation of ferrous iron plays an important role in the mobility and availability of iron to the legume. In the present study, we investigated the iron-binding properties of low-molecular weight succinoglycans isolated from the nitrogen-fixing bacterium, Sinorhizobium meliloti. The low-molecular weight succinoglycans comprising three monomers (M1-M3), four dimers (D1-D4), and six trimers (T1-T6) of the succinoglycan repeating unit were purified by various chromatographic techniques. Interestingly, the colorimetric ferrozine method showed that the succinoglycans T6, M3, and D3 demonstrated a ferrous iron chelating ability of 83, 63, and 38 % per mg, respectively. The individual binding constants were determined as 43703, 2313, and 760 M(-1) for succinoglycans T6, M3, and D3 using ultraviolet-visible spectroscopy. The complexation of succinoglycan and ferrous iron can cause structural changes, which were analyzed by circular dichroism spectroscopy. Furthermore, the complex could provide antioxidant activity through an anti-Fenton reaction. These results demonstrate that the low-molecular weight succinoglycans can effectively modulate iron biochemistry as a novel ferrous iron-acquisition system of S. meliloti.

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

    PubMed

    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.

  13. Reversible immobilization of invertase on Cu-chelated polyvinylimidazole-grafted iron oxide nanoparticles.

    PubMed

    Uzun, Kerem; Çevik, Emre; Şenel, Mehmet; Baykal, Abdülhadi

    2013-12-01

    Polyvinylimidazole (PVI)-grafted iron oxide nanoparticles (PVIgMNP) were prepared by grafting of telomere of PVI on the iron oxide nanoparticles. Different metal ions (Cu(2+), Zn(2+), Cr(2+), Ni(2+)) ions were chelated on polyvinylimidazole-grafted iron oxide nanoparticles, and then the metal-chelated magnetic particles were used in the adsorption of invertase. The maximum invertase immobilization capacity of the PVIgMNP-Cu(2+) beads was observed to be 142.856 mg/g (invertase/PVIgMNP) at pH 5.0. The values of the maximum reaction rate (V max) and Michaelis-Menten constant (Km) were determined for the free and immobilized enzymes. The enzyme adsorption-desorption studies, pH effect on the adsorption efficiency, affinity of different metal ions, the kinetic parameters and storage stability of free and immobilized enzymes were evaluated.

  14. Preparation, Identification and Antioxidant Properties of Black-Bone Silky Fowl (Gallus gallus domesticus Brisson) Iron(II)-Oligopeptide Chelate

    PubMed Central

    Pan, Huanglei; Song, Shasha; Ma, Qiuyue; Wei, Hui; Ren, Difeng; Lu, Jun

    2016-01-01

    Summary Black-bone silky fowl iron(II)-oligopeptide chelate was synthesized from iron(II) solution and the black-bone silky fowl oligopeptide, which was extracted from the muscle protein of black-bone silky fowl (Gallus gallus domesticus Brisson). Orthogonal array analysis was used to determine the optimal conditions for the iron(II)-oligopeptide chelate preparation. Ultraviolet-visible (UV-Vis) spectroscopy, electron microscopy, and Fourier transform infrared (FTIR) spectroscopy were used to identify the structure of iron(II)-oligopeptide chelate. 2-Diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging assays were performed to compare the antioxidant abilities of the black-bone silky fowl oligopeptide and iron(II)-oligopeptide chelate. The optimal conditions for iron(II)-oligopeptide chelate preparation were 4% of the black-bone silky fowl oligopeptide and a ratio of the black- -bone silky fowl oligopeptide to FeCl2·4H2O of 5:1 at pH=4. Under these conditions, the chelation rate was (84.9±0.2) % (p<0.05), and the chelation yield was (40.3±0.1) % (p<0.05). The structures detected with UV-Vis spectroscopy, electron microscopy and FTIR spectra changed significantly after chelation, suggesting that Fe(II) ions formed coordinate bonds with carboxylate (-RCOOŻ) and amino (-NH2) groups in the oligopeptides, confirming that this is a new oligopeptide-iron chelate. The iron(II)-oligopeptide chelate had stronger scavenging activity towards DPPH and superoxide radicals than did the black-bone silky fowl oligopeptide. PMID:27904406

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

    PubMed Central

    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

  16. Detection of decontamination solution chelating agents using ion selective coated-wire electrodes

    SciTech Connect

    Banks, M.L.

    1992-12-31

    This thesis explores feasibility of using coated-wire electrodes to measure chelating agent concentration. Chelating agents are often found in radioactive decontamination solutions because they aid in the removal of radionuclides from contaminated surfaces by increasing their solubility. However, this characteristic will also enhance the mobility of the radionuclide and thus its transport out of a waste disposal site. Coated-wire ion selective electrodes, based on a polyvinylchloride membrane using dioctylphthalate as a plasticizer and dinonylnaphthalenesulfonic acid as a counterion, were constructed for five commonly utilized chelating agents (ethylenediaminetetracetic acid (EDTA), nitrilotriacetic acid (NTA), citric acid, oxalic acid and tartaric add). The EDTA and NTA electrodes` calibration characteristics exhibited acceptable behavior in pure standard solutions. From data obtained while using the EDTA and NTA electrodes in a cement environment, further research needs to be done in the area of ion interference.

  17. Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

    PubMed Central

    Cloonan, Suzanne M.; Glass, Kimberly; Laucho-Contreras, Maria E.; Bhashyam, Abhiram R.; Cervo, Morgan; Pabón, Maria A.; Konrad, Csaba; Polverino, Francesca; Siempos, Ilias I.; Perez, Elizabeth; Mizumura, Kenji; Ghosh, Manik C.; Parameswaran, Harikrishnan; Williams, Niamh C.; Rooney, Kristen T.; Chen, Zhi-Hua; Goldklang, Monica P.; Yuan, Guo-Cheng; Moore, Stephen C.; Demeo, Dawn L.; Rouault, Tracey A.; D’Armiento, Jeanine M.; Schon, Eric A.; Manfredi, Giovanni; Quackenbush, John; Mahmood, Ashfaq; Silverman, Edwin K.; Owen, Caroline A.; Choi, Augustine M.K.

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. PMID:26752519

  18. Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages

    SciTech Connect

    Brock, J.H.; Liceaga, J.; Arthur, H.M.; Kontoghiorghes, G.J. )

    1990-05-01

    The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2-dimethyl (L1) and 1-ethyl-2-methyl (L1NEt) derivatives of 3-hydroxypyrid-4-one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe-transferrin-antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic alpha-ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine.

  19. Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages.

    PubMed

    Brock, J H; Licéaga, J; Arthur, H M; Kontoghiorghes, G J

    1990-05-01

    The effect of several iron chelators on iron uptake and release by mouse peritoneal macrophages has been investigated. The 1,2-dimethyl (L1) and 1-ethyl-2-methyl (L1NEt) derivatives of 3-hydroxypyrid-4-one markedly enhanced iron mobilisation from macrophages pulsed with 59Fe-transferrin-antitransferrin immune complexes and were more effective than desferrioxamine, maltol, or mimosine. Release increased with increasing chelator concentration. None of the chelators donated significant amounts of iron to macrophages, and none showed any cytotoxic effect. The synthetic alpha-ketohydroxypyridine chelators may therefore be active in removing iron from the reticuloendothelial system as well as from hepatocytes, and indeed may be superior to desferrioxamine.

  20. Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for (225)Ac radioimmunotherapy applications.

    PubMed

    Chappell, L L; Deal, K A; Dadachova, E; Brechbiel, M W

    2000-01-01

    225Ac (t(1/2) = 10 days) is an alternative alpha-emitter that has been proposed for radioimmunotherapy (RIT) due to its many favorable properties, such as half-life and mode of decay. The factor limiting use of (225)Ac in RIT is the lack of an acceptably stable chelate for in vivo applications. Herein is described the first reported bifunctional chelate for (225)Ac that has been evaluated for stability for in vivo applications. The detailed synthesis of a bifunctional chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane- 1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to-protein ratios between 1.4 and 2. The three conjugates were radiolabeled with (225)Ac, and serum stability study of the [(225)Ac]BL-3-HEHA conjugate was performed.

  1. Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats

    SciTech Connect

    Klaassen, C.D.; Waalkes, M.P.; Cantilena, L.R. Jr.

    1984-03-01

    The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

  2. Australian guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell disease and other congenital anaemias.

    PubMed

    Ho, P J; Tay, L; Lindeman, R; Catley, L; Bowden, D K

    2011-07-01

    Iron overload is the most important cause of mortality in patients with thalassaemia major. Iron chelation is therefore a critical issue in the management of these patients and others with transfusion-dependent haemoglobinopathies and congenital anaemias. In recent years, significant developments have been made in the assessment of iron overload, including the use of magnetic resonance imaging for measuring liver and cardiac iron. Advances in the modalities available for iron chelation, with the advent of oral iron chelators including deferiprone and deferasirox in addition to parenteral desferrioxamine, have expanded treatment options. A group of Australian haematologists has convened to formulate guidelines for managing iron overload on the basis of available evidence, and to describe best consensus practice as undertaken in major Australian Haemoglobinopathy units. The results of their discussions are described in this article, with the aim of providing guidance in the management of iron overload in these patients.

  3. Chelating Properties of Peptides from Red Seaweed Pyropia columbina and Its Effect on Iron Bio-Accessibility.

    PubMed

    Cian, Raúl E; Garzón, Antonela G; Ancona, David Betancur; Guerrero, Luis Chel; Drago, Silvina R

    2016-03-01

    The aim of this work was to evaluate copper-chelating, iron-chelating and anticariogenic activity of peptides obtained by enzymatic hydrolysis of P. columbina protein concentrate and to study the effects of chelating peptides on iron bio-accessibility. Two hydrolyzates were obtained from P. columbina protein concentrate (PC) using two hydrolysis systems: alkaline protease (A) and alkaline protease + Flavourzyme (AF). FPLC gel filtration profile of PC shows a peak having molecular weight (MW) higher than 7000 Da (proteins). A and AF hydrolyzates had peptides with medium and low MW (1013 and 270 Da), respectively. Additionally, AF presented free amino acids with MW around 82 Da and higher content of His and Ser. Peptides from AF showed the highest chelating properties measured as copper-chelating activity (the lowest β-carotene oxidation rate: Ro; 0.7 min(-1)), iron-chelating activity (33%), and phosphorous and Ca(2+) release inhibition (87 and 81%, respectively). These properties could indicate antioxidant properties, promotion of iron absorption and anticariogenic activity, respectively. In fact, hydrolyzates promoted iron dialyzability (≈ 16%), values being higher than that found for P. columbina seaweed. Chelating peptides from both hydrolyzates can maintain the iron in a soluble and bio-accessible form after gastrointestinal digestion.

  4. Antimicrobial action of chelating agents: repercussions on the microorganism development, virulence and pathogenesis.

    PubMed

    Santos, A L S; Sodre, C L; Valle, R S; Silva, B A; Abi-Chacra, E A; Silva, L V; Souza-Goncalves, A L; Sangenito, L S; Goncalves, D S; Souza, L O P; Palmeira, V F; d'Avila-Levy, C M; Kneipp, L F; Kellett, A; McCann, M; Branquinha, M H

    2012-01-01

    Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.

  5. Stabilization of heavy metals in contaminated sediments using organic chelating agents.

    PubMed

    Xu, Ying; Fang, Sheng-Rong

    2015-01-01

    A stabilization treatment for heavy metals in sediments was developed using the heavy metal chelators ammonium dipropyl dithiophosphate (ADD) and potassium diisopropyl dithiophosphate (PDD). The results indicate that 7% ADD and 7% PDD achieved Pb and Cu stabilization rates of up to 99%, Cd stabilization rates of 78% and 95%, and Zn stabilization rates of 21 and 51%, respectively. At pH levels ranging from 2 to 12, the amount of heavy metals in leachate from the stabilized product using the chelating agents were significantly less than those using Na2S and Na3PO4. After treatment, the chelating agents were mainly bound to the exchangeable fraction of heavy metals in the sediment and formed stable bonds with organic matter, thus significantly reducing the biological risks of heavy metals in sediment.

  6. Ascorbate-dependent formation of hydroxyl radicals in the presence of iron chelates.

    PubMed

    Prabhu, H R; Krishnamurthy, S

    1993-10-01

    The autoxidation of L-ascorbate on incubation in saline phosphate buffer (pH 7.4) is accompanied by hydroxyl radical (.OH) generation. The metal chelator EDTA showed significant inhibition of ascorbate autoxidation and ascorbate-dependent .OH release. On the other hand, Fe2+ (EDTA) greatly augmented both ascorbate autoxidation and ascorbate-dependent .OH production. The biological iron chelating compounds such as ATP, ADP, citrate and pyrophosphate suppressed both ascorbate autoxidation and ascorbate-mediated .OH production, thereby indicating that these compounds suppress the activating effect of iron. Ascorbate autoxidation and ascorbate-dependent .OH formation, stimulated by Fe2+ (EDTA) were significantly inhibited by .OH scavengers, namely mannitol, thiourea and sodium formate, as well as by catalase and to a lesser extent by bovine serum albumin, superoxide dismutase (native and heat denatured) and heat denatured catalase.

  7. Iron release and membrane damage in erythrocytes exposed to oxidizing agents, phenylhydrazine, divicine and isouramil.

    PubMed Central

    Ferrali, M; Signorini, C; Ciccoli, L; Comporti, M

    1992-01-01

    Mouse erythrocytes were incubated with oxidizing agents, phenylhydrazine, divicine and isouramil. With all the oxidants a rapid release of iron in a desferrioxamine (DFO)-chelatable form was seen and it was accompanied by methaemoglobin formation. If the erythrocytes were depleted of GSH by a short preincubation with diethyl maleate, the release of iron was accompanied by lipid peroxidation and, subsequently, haemolysis. GSH depletion by itself did not induce iron release, methaemoglobin formation, lipid peroxidation or haemolysis. Rather, the fate of the cell in which iron is released depended on the intracellular availability of GSH. In addition, iron release was higher in depleted cells than in native ones, suggesting a role for GSH in preventing iron release when oxidative stress is imposed by the oxidants. Iron release preceded lipid peroxidation. The latter was prevented when the erythrocytes were preloaded with DFO in such a way (preincubation with 10 mM-DFO) that the intracellular concentration was equivalent to that of the released iron, but not when the intracellular DFO was lower (preincubation with 0.1 mM-DFO). Extracellular DFO did not affect lipid peroxidation and haemolysis, suggesting again that the observed events occur intracellularly (intracellular chelation of released iron). The relevance of iron release from iron complexes in the mechanisms of cellular damage induced by oxidative stress is discussed. PMID:1637315

  8. Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

    PubMed Central

    Fortin, Patricia M; Madgwick, Karen V; Trivella, Marialena; Hopewell, Sally; Doree, Carolyn; Estcourt, Lise J

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To identify and assess the effectiveness of interventions to improve adherence to iron chelation therapy compared to standard care in people with SCD or thalassaemia including: identifying and assessing the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions);identifying and assessing the effectiveness of interventions specific to different age groups (children, adolescents, adults). PMID:27713668

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

    PubMed Central

    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

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

    PubMed

    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.

  11. Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

    NASA Astrophysics Data System (ADS)

    Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

    2007-12-01

    Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil

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

    PubMed

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

    2016-09-01

    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.

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

    PubMed Central

    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

  14. Biodegradable chelating agents for industrial, domestic, and agricultural applications--a review.

    PubMed

    Pinto, Isabel S S; Neto, Isabel F F; Soares, Helena M V M

    2014-10-01

    Aminopolycarboxylates, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), are chelating agents widely used in several industrial, agricultural, and domestic applications. However, the fact that they are not biodegradable leads to the presence of considerable amounts in aquatic systems, with serious environmental consequences. The replacement of these compounds by biodegradable alternatives has been the object of study in the last three decades. This paper reviews the most relevant studies towards the use of environmentally friendly chelating agents in a large number of applications: oxidative bleaching, detergents and cleaning compositions, scale prevention and reduction, remediation of soils, agriculture, electroplating, waste treatment, and biocides. Nitrilotriacetic acid (NTA), ethylenediaminedisuccinic acid (EDDS), and iminodisuccinic acid (IDS) are the most commonly suggested to replace the nonbiodegradable chelating agents. Depending on the application, the requirements for metal complexation might differ. Metal chelation ability of the most promising compounds [NTA, EDDS, IDS, methylglycinediacetic acid (MGDA), L-glutamic acid N,N-diacetic acid (GLDA), ethylenediamine-N,N'-diglutaric acid (EDDG), ethylenediamine-N,N'-dimalonic acid (EDDM), 3-hydroxy-2,2-iminodisuccinic acid (HIDS), 2-hydroxyethyliminodiacetic acid (HEIDA), pyridine-2,6-dicarboxylic acid (PDA)] with Fe, Mn, Cu, Pb, Cd, Zn, Ca, and Mg was simulated by computer calculations. The advantages or disadvantages of each compound for the most important applications were discussed.

  15. [Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

    PubMed

    Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

    2007-09-01

    The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

  16. [Remediation of Cu-Pb-contaminated loess soil by leaching with chelating agent and biosurfactant].

    PubMed

    Liu, Xia; Wang, Jian-Tao; Zhang, Meng; Wang, Li; Yang, Ya-Ti

    2013-04-01

    Because of its strong chelation, solubilization characteristics, the chelating agents and biosurfactant are widely used in remediation of heavy metals and organic contaminated soils. Ethylenediamine tetraacetic acid (EDTA), citric acid (CIT) and dirhamnolipid (RL2) were selected as the eluent. Batch experiments and column experiments were conducted to investigate the leaching effect of the three kinds of eluent, as well as the mixture of biosurfactant and chelating agent for Cu, Pb contaminated loess soil. The results showed that the leaching efficiencies of different eluent on Cu, Pb contaminated loess soil followed the sequence of EDTA > CIT > RL2. At an eluent concentration of 0.02 mol x L(-1), the Cu leaching efficiency was 62.74% (EDTA), 52.28% (CIT) and 15.35% (RL2), respectively; the Pb leaching efficiency was 96.10% (EDTA), 23.08% (CIT) and 14.42% (RL2), respectively. When the concentration of RL2 was 100 CMC, it had synergistic effects on the other two kinds of chelating agent in Cu leaching, and when the concentration of RL2 was 200 CMC, it had antagonism effects. The effect of RL2 on EDTA in Pb leaching was similar to that in Cu leaching. Pb leaching by CIT was inhibited in the presence of RL2. EDTA and CIT could effectively remove Cu and Pb in exchangeable states, adsorption states, carbonate salts and organic bound forms; RL2 could effectively remove Cu and Pb in exchangeable and adsorbed states.

  17. Chelating agents related to ethylenediamine bis(2-hydroxyphenyl)acetic acid (EDDHA): synthesis, characterization, and equilibrium studies of the free ligands and their Mg2+, Ca2+, Cu2+, and Fe3+ chelates.

    PubMed

    Yunta, Felipe; García-Marco, Sonia; Lucena, Juan J; Gómez-Gallego, Mar; Alcázar, Roberto; Sierra, Miguel A

    2003-08-25

    Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenyl)acetic acid (EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soils. EDDHA, EDDH4MA (ethylenediamine-N,N'-bis(2-hydroxy-4-methylphenyl)acetic acid), and EDDCHA (ethylenediamine-N,N'-bis(2-hydroxy-5-carboxyphenyl)acetic acid) are allowed by the European directive, but also EDDHSA (ethylenediamine-N,N'-bis(2-hydroxy-5-sulfonylphenyl)acetic acid) and EDDH5MA (ethylenediamine-N,N'-bis(2-hydroxy-5-methylphenyl)acetic acid) are present in several commercial iron chelates. In this study, these chelating agents as well as p,p-EDDHA (ethylenediamine-N,N'-bis(4-hydroxyphenyl)acetic acid) and EDDMtxA (ethylenediamine-N,N'-bis(2-metoxyphenyl)acetic acid) have been obtained following a new synthetic pathway. Their chemical behavior has been studied to predict the effect of the substituents in the benzene ring on their efficacy as iron fertilizers for soils above pH 7. The purity of the chelating agents has been determined using a novel methodology through spectrophotometric titration at 480 nm with Fe(3+) as titrant to evaluate the inorganic impurities. The protonation constants were determined by both spectrophotometric and potentiometric methods, and Ca(2+) and Mg(2+) stability constants were determined from potentiometric titrations. To establish the Fe(3+) and Cu(2+) stability constants, a new spectrophotometric method has been developed, and the results were compared with those reported in the literature for EDDHA and EDDHMA and their meso- and rac-isomers. pM values have been also determined to provide a comparable basis to establish the relative chelating ability of these ligands. The purity obtained for the ligands is higher than 87% in all cases and is comparable with that obtained by (1)H NMR. No significant differences have been found among ligands when their protonation and stability constants were compared. As expected, no Fe(3

  18. Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

    SciTech Connect

    Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C. )

    1990-12-01

    The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications.

    PubMed

    Farmaki, Kallistheni; Tzoumari, Ioanna; Pappa, Christina

    2011-06-15

    Combined chelation treatment may be a better approach for transfusion-dependent thalassemia major patients with iron overload complications because of increased efficacy. Combination therapy with desferrioxamine and deferiprone has already been reported to improve survival dramatically by reversing cardiac dysfunction and other endocrine complications. Some patients have intolerance or inconvenience to parenteral desferrioxamine. The hypothesis of this study was that combining two oral chelators, deferiprone and deferasirox, might lead to similar results. Following approval by the hospital ethical committee and a written informed consent from each patient, 16 patients who fulfilled the criteria participated in a study protocol for a period of up to 2 years. Efficacy measures analysis demonstrated a statistically significant decrease of total body iron load as estimated by serum ferritin, LIC and MRI T2* indices. Regarding the safety assessment, the incidence of adverse events was minor compared to the associated toxicity of monotherapy of each drug. No new onset of iron overload-related complications was demonstrated. A reversal of cardiac dysfunction was observed in 2/4 patients, while the mean LVEF increased significantly. Regarding endocrine assessment, in 2/8 patients with impaired glucose tolerance, we noted a significant decrease in the mean 2h glucose in OGTT. Additionally an improvement in gonadal function was observed and one male and one female gave birth to two healthy children without hormonal stimulation. Combined oral chelation in thalassemia offers the promise of easier administration, better compliance and may lead to an improvement of patient quality of life by preventing or even reversing iron overload complications.

  1. Influence of chelating agents on the distribution and excretion of cadmium in rats

    SciTech Connect

    Planas-Bohne, F.; Lehmann, M.

    1983-03-15

    The effects of the chelating agents CaNa2-ethylenediaminetetraacetate (EDTA), CaNa3-diethylenetriaminepentaacetate (DTPA), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropanol (BAL), and 2,3-dimercaptopropane-1-sulfonate (DMPS) and of the lipophilic chelating agents Puchel, Puchel-bisamidocysteineethyl ester (Puch-D), and EDTA-bis-amidocysteineethyl ester (EDTA-D) on the distribution of iv injected Cd were studied in male Sprague-Dawley rats. The chelating agents were injected iv as single doses given 10 sec, 1 hr, or 3 hr after 3 mumol/kg Cd + 115mCd. When the chelating agents were injected within 10 sec after the metal, all agents reduced the total body cadmium burden by varying extents ranging from 3% of that in untreated control rats after 0.01 mmol BAL/kg to 94% following 0.1 mmol DTPA/kg. When given 1 hr after Cd injection, the efficacy of all the agents tested was markedly reduced or abolished; at this time only Puchel and Puch-D provoked significant reductions in the body burden of Cd by 21 and 32%, respectively. When treatment was delayed until 3 hr after Cd injection, only Puch-D was able to reduce the body and liver burden of the metal by 14 and 9%, respectively. Combined treatment with Puchel + DTPA, BAL + DTPA, or BAL + DMPS did not enhance Cd removal to an extent greater than that expected from the equivalent dose of the more effective agent of that pair alone. Repeated administration of DTPA, 20 X 0.1 mmol/kg, during 4 weeks by ip or po administration of the same dose in the drinking water over 4 weeks, was no no more effective than the first dose of the chelating agent alone. Gel chromatographic studies of the distribution of Cd among the proteins of the liver cytosol in treated and untreated animals indicate that neither DTPA nor Puchel was able to release Cd from the metallothionein complex.

  2. Iron regulated outer membrane proteins of Escherichia coli: variations in expression due to the chelator used to restrict the availability of iron.

    PubMed

    Chart, H; Buck, M; Stevenson, P; Griffiths, E

    1986-05-01

    Iron restriction was induced in Escherichia coli O 111, E. coli O 164 and E. coli C by growing the organisms in trypticase soy broth containing ovotransferrin, desferal, EDDA (ethylenediamine-dihydroxyphenylacetic acid) or alpha,alpha'-dipyridyl. There were marked qualitative and quantitative differences in the iron regulated outer membrane proteins expressed in the presence of the various iron chelators. Differences in the kinetics of growth were also noted. E. coli C was devoid of a ferric enterobactin iron uptake system.

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

    PubMed

    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 EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P < 0.05). Obviously, the level of 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

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

    PubMed

    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.

  5. Degradation of chelating agents in aqueous solution using advanced oxidation process (AOP).

    PubMed

    Sillanpää, Mika E T; Kurniawan, Tonni Agustiono; Lo, Wai-hung

    2011-06-01

    This article presents an overview with critical analysis of technical applicability of advanced oxidation process (AOP) in removing chelating agents from aqueous solution. Apart from the effect of metals for chelating agents as a major influencing factor, selected information such as pH, oxidant's dose, concentrations of pollutants and treatment performance is presented. The performance of individual AOP is compared. It is evident from our literature survey that photocatalysis with UV irradiation alone or coupled with TiO(2), ozonation and Fenton's oxidation are frequently applied to mineralize target pollutants. Overall, the selection of the most suitable AOP depends on the characteristics of effluents, technical applicability, discharge standard, regulatory requirements and environmental impacts.

  6. Effects of temperature and chelating agents on cadmium uptake in the American oyster

    SciTech Connect

    Hung, Y.W.

    1982-05-01

    The effect of temperature on cadmium accumulations was evaluated in the tissue of the American oyster, Crassostrea virginica, under controlled laboratory conditions. Oysters have been reported to accumulate cadmium from seawater containing added cadmium chloride. However, the chemical form of cadmium in seawater has not been defined. This may profoundly influence the mechanism of uptake. Therefore, the report is also concerned with the effect of chelating agents on the uptake of cadmium. Chelating agents used were nitrilotriacetic acid, ethylene diaminetetraacetic acid and humic acid. At the end of a 40-day exposure to cadmium, 15 oysters were randomly selected from each tank of synthetic seawater, and each was dissected into 5 fractions, namely gills, mantle, adductor muscle, hepatopancreas and the remainder. The cadmium content of each fraction was analyzed by atomic absorption spectrophotometry with a flameless graphite furnace. (JMT)

  7. Enhanced uptake of As, Zn, and Cu by Vetiveria zizanioides and Zea mays using chelating agents.

    PubMed

    Chiu, K K; Ye, Z H; Wong, M H

    2005-09-01

    Vetiveria zizaniodes (vetiver) is commonly known for its effectiveness in soil and sediment erosion control. It can tolerate to extreme soil conditions and produce a high biomass even growing in contaminated areas. Zea mays (maize) can also produce a very high biomass with a fast growth rate and possesses some degree of metal tolerance. A greenhouse study was conducted to investigate the feasibility of using vetiver and maize for remediation of arsenic (As)-, zinc (Zn-), and copper (Cu)-amended soils and evaluate the effects of chelating agents on metal uptake by these plants. Vetiver had a better growth (dry weight yield of root and shoot) than maize under different treatment conditions. The effects of different chelating agents on As, Zn, and Cu extraction from soil to soil solution were studied. Among the nine chelating agents used, it was noted that 20 mmol NTA could maximize As and Zn bioavailability, while 20 mmol HEIDA could maximize Cu bioavailability in the soil solution. The surge time in maximizing metal uptake ranged from 16 to 20 days which indicated that timing on plant harvest was an important factor in enhanced metal accumulation. In general, vetiver was a more suitable plant species than maize in terms of phytoextraction of metals from metal-contaminated soil. Application of NTA in As-amended soil and HEIDA in Cu-amended soil at the rate of 20 mmol kg(-1) increased 3-4-fold of As and Cu in shoot of both plants, whereas application of NTA (20 mmol kg(-1)) increased 37- and 1.5-fold of Zn accumulation in shoot of vetiver and maize, respectively. The potential environmental risk of metal mobility caused by chelating agents used for phytoextraction should not be overlooked.

  8. Solution mining dawsonite from hydrocarbon containing formations with a chelating agent

    DOEpatents

    Vinegar, Harold J.

    2009-07-07

    A method for treating an oil shale formation comprising dawsonite includes providing heat from one or more heaters to the formation to heat the formation. Hydrocarbon fluids are produced from the formation. At least some dawsonite in the formation is decomposed with the provided heat. A chelating agent is provided to the formation to dissolve at least some dawsonite decomposition products. The dissolved dawsonite decomposition products are produced from the formation.

  9. Mechanism of action of diabetogenic zinc-chelating agents. Model system studies.

    PubMed

    Epand, R M; Stafford, A R; Tyers, M; Nieboer, E

    1985-03-01

    Using model systems, we have studied the properties of a number of zinc-chelating agents which are known to cause diabetes in laboratory animals. The abilities to permeate membranes and to complex zinc inside liposomes with the release of protons are suggested as chemical properties that can enhance diabetogenicity. When such complexing agents are added to lipid vesicles at pH 6 containing entrapped zinc ions, they acidify the contents of these vesicles. We have demonstrated this effect by measuring intravesicular pH both with a fluorine-containing F NMR probe as well as with the fluorescent probe, quinine. For example, using quinine, we observed that 0.1 mM 8-hydroxyquinoline reduced the intravesicular pH of sonicated phospholipid vesicles containing entrapped Zn2+ (as sulfate) from pH 6.0 to 2.8. These diabetogenic chelating agents also solubilized zinc-insulin precipitates from unbuffered suspensions at pH 6.0. The solubilization results from the acidification of these suspensions. Dithizone and 8-hydroxyquinoline at 4 mM solubilized 97 and 42%, respectively, of the suspended insulin. We suggest that if such proton release occurs within the zinc-containing insulin storage granules of pancreatic beta-cells, solubilization of insulin would be induced. Such an event would lead to osmotic stress and eventually to rupture of the granule. The effects of diethyldithiocarbamate (DDC), an agent that has been found to protect rabbits against the induction of diabetes by some other zinc-chelating agents, were also studied. DDC caused a decrease of 3.5 units in the intravesicular pH of zinc-containing vesicles by a mechanism not involving the release of protons upon chelation of zinc. We have demonstrated several properties of DDC which may contribute to its ability to protect against the induction of diabetes. These include its ability to store zinc as a hydrophobic complex in membranes, its consumption of protons upon spontaneous decomposition, and the ability of one of

  10. [Physico-chemical and toxicological profile of gadolinium chelates as contrast agents for magnetic resonance imaging].

    PubMed

    Idée, J-M; Fretellier, N; Thurnher, M M; Bonnemain, B; Corot, C

    2015-07-01

    Gadolinium chelates (GC) are contrast agents widely used to facilitate or to enable diagnosis using magnetic resonance imaging (MRI). From a regulatory viewpoint, GC are drugs. GC have largely contributed to the success of MRI, which has become a major component of clinician's diagnostic armamentarium. GC are not metabolised and are excreted by the kidneys. They distribute into the extracellular compartment. Because of its high intrinsic toxicity, gadolinium must be administered as a chelate. GC can be classified according to two key molecular features: (a) nature of the chelating moiety: either macrocyclic molecules in which gadolinium is caged in the pre-organized cavity of the ligand, or linear, open-chain molecules, (b) ionicity: Gd chelates can be ionic (meglumine or sodium salts) or non-ionic. The thermodynamic and kinetic stabilities of the various GCs differ according to these structural characteristics. The kinetic stability of macrocyclic GCs is much higher than that of linear GCs and the thermodynamic stability of ionic GCs is generally higher than that of non-ionic GC, thus leading to a lower risk of gadolinium dissociation. This class of drugs has enjoyed an excellent reputation in terms of safety for a long time, until a causal link with a recently-described serious disease, nephrogenic systemic fibrosis (NSF), was evidenced. It is acknowledged that the vast majority of NSF cases are related to the administration of some linear CG in renally-impaired patients. Health authorities, worldwide, released recommendations which drastically reduced the occurrence of new cases.

  11. The iron-chelating potential of silybin in patients with hereditary haemochromatosis.

    PubMed

    Hutchinson, C; Bomford, A; Geissler, C A

    2010-10-01

    Milk thistle contains silybin, which is a potential iron chelator. We aimed to determine whether silybin reduced iron absorption in patients with hereditary haemochromatosis. In this crossover study, on three separate occasions, 10 patients who were homozygous for the C282Y mutation in the HFE gene (and fully treated) consumed a vegetarian meal containing 13.9 mg iron with: 200 ml water; 200 ml water and 140 mg silybin (Legalon Forte); or 200 ml tea. Blood was drawn once before, then 0.5, 1, 2, 3 and 4 h after the meal. Consumption of silybin with a meal resulted in a reduction in the postprandial increase in serum iron (AUC±s.e.) compared with water (silybin 1726.6±346.8 versus water 2988.8±167; P<0.05) and tea (silybin 1726.6±346.8 versus tea 2099.3±223.3; P<0.05). In conclusion, silybin has the potential to reduce iron absorption, and this deserves further investigation, as silybin could be an adjunct in the treatment of haemochromatosis.

  12. Iron chelation by cranberry juice and its impact on Escherichia coli growth.

    PubMed

    Lin, Baochuan; Johnson, Brandy J; Rubin, Robert A; Malanoski, Anthony P; Ligler, Frances S

    2011-01-01

    The various health benefits of Vaccinium macrocarpon (cranberry) are well documented and have been attributed mainly to its antioxidant capacity and anti-adhesive activity. Several different mechanisms have been proposed to explain the possible role of cranberries, cranberry juice, and cranberry extracts in inhibiting bacterial growth. These mechanisms of action (i.e., inhibition of the microbial growth) have not been thoroughly studied. Here, we took advantage of current advances in microarray technology and used GeneChip® Escherichia coli genome 2.0 arrays to gain insight into the molecular mechanisms involved in the impact of cranberry juice on the properties of E. coli growth. The inclusion of cranberry juice in bacterial growth media was found to significantly impact the doubling time of E. coli. The gene expression results revealed altered expression of genes associated with iron transport and essential metabolic enzymes as well as with adenosine triphosphate (ATP) synthesis and fumarate hydratase in these cultures. The altered expression of genes associated with iron transport was consistent with the strong iron chelating capability of proanthocyanidins, a major constituent of cranberry juice. The iron depletion effect was confirmed by adding exogenous iron to the growth media. This addition partially reversed the inhibitory effect on bacterial growth observed in the presence of cranberry juice/extracts.

  13. Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

    PubMed Central

    Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C.; Blower, Philip J.; Ma, Michelle T.

    2017-01-01

    Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images. PMID:28075350

  14. Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of oxidative stress in stroke patients.

    PubMed

    Selim, Magdy

    2010-03-01

    The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective effects, mediated via suppression of iron-induced hydroxyl radical formation, in various animal models of ischemic and hemorrhagic stroke. Therefore, the objective of this study was to investigate whether DFO can exert similar actions in stroke patients, by examining the effects of treatment with DFO on biological markers of oxidative stress, namely serum total hydroperoxides and lipoperoxides and total radical trapping antioxidant capacity (TRAP), in stroke patients. We found that serum levels of peroxides were reduced, and TRAP levels increased after a 3-day treatment with DFO (500 mg). These findings provide a preliminary proof of concept that DFO can exert potential antioxidant neuroprotective effects in stroke patients. Future, larger-scale, randomized, and controlled studies to further evaluate the safety and efficacy of DFO in patients with stroke are warranted.

  15. The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles.

    PubMed

    Qaisar, Uzma; Kruczek, Cassandra J; Azeem, Muhammed; Javaid, Nasir; Colmer-Hamood, Jane A; Hamood, Abdul N

    2016-08-01

    Proteins encoded by the Pseudomonas aeruginosa pvcA-D operon synthesize a novel isonitrile functionalized cumarin termed paerucumarin. The pvcA-D operon enhances the expression of the P. aeruginosa fimbrial chaperone/usher pathway (cup) genes and this effect is mediated through paerucumarin. Whether pvcA-D and/or paerucumarin affect the expression of other P. aeruginosa genes is not known. In this study, we examined the effect of a mutation in pvcA-D operon the global transcriptome of the P. aeruginosa strain PAO1-UW. The mutation reduced the expression of several ironcontrolled genes including pvdS, which is essential for the expression of the pyoverdine genes. Additional transcriptional studies showed that the pvcA-D operon is not regulated by iron. Exogenously added paerucumarin enhanced pyoverdine production and pvdS expression in PAO1-UW. Iron-chelation experiments revealed that purified paerucumarin chelates iron. However, exogenously added paerucumarin significantly reduced the growth of a P. aeruginosa mutant defective in pyoverdine and pyochelin production. In contrast to other secondary metabolite, Pseudomonas quinolone signal (PQS), paerucumarin is not localized to the P. aeruginosa membrane vesicles. These results suggest that paerucumarin enhances the expression of iron-controlled genes by chelating iron within the P. aeruginosa extracellular environment. Although paerucumarin chelates iron, it does not function as a siderophore. Unlike PQS, paerucumarin is not associated with the P. aeruginosa cell envelope.

  16. 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

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    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 the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID:26893541

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

    PubMed Central

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

    2016-01-01

    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. PMID:27671769

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Comparison of different chelating agents to enhance reductive Cr(VI) removal by pyrite treatment procedure.

    PubMed

    Kantar, Cetin; Ari, Cihan; Keskin, Selda

    2015-06-01

    New technologies involving in-situ chemical hexavalent chromium [Cr(VI)] reduction to trivalent chromium [Cr(III)] with natural Fe(II)-containing minerals can offer viable solutions to the treatment of wastewater and subsurface systems contaminated with Cr(VI). Here, the effects of five different chelating agents including citrate, EDTA, oxalate, tartrate and salicylate on reductive Cr(VI) removal from aqueous systems by pyrite were investigated in batch reactors. The Cr(VI) removal was highly dependent on the type of ligand used and chemical conditions (e.g., ligand concentration). While salicylate and EDTA had no or little effect on Cr(VI) removal, the ligands including citrate, tartrate and oxalate significantly enhanced Cr(VI) removal at pH < 7 relative to non-ligand systems. In general, the efficiency of organic ligands on Cr(VI) removal decreased in the order: citrate ≥ oxalate ≈ tartrate > EDTA > salicylate ≈ non-ligand system. Organic ligands enhanced Cr(VI) removal by 1) removing surface oxide layer via the formation of soluble Fe-Cr-ligand complexes, and 2) enhancing the reductive iron redox cycling for the regeneration of new surface sites. While citrate, oxalate and tartrate eliminated the formation of surface Cr (III)-Fe(III)-oxides, the surface phase Cr (III) species was observed in the presence of EDTA and salicylate indicating that Cr(III) complexed with EDTA and salicylate sorbed or precipitated onto pyrite surface, thereby blocking the access of CrO4(2-) to pyrite surface. The binding of Fe(III) with the disulfide reactive sites (≡Fe-S-S-Fe(III)) was essential for the regeneration of new surface sites through pyrite oxidation. Although Fe(III)-S species was detected at the pyrite surface in the presence of citrate, oxalate and tartrate, Fe(III) complexed with EDTA and salicylate did not strongly interact with the disulfide reactive sites due to the formation of non-sorbing Fe(III)-ligand complexes. The absence of surface Fe

  20. Overexpression of the FRO2 ferric chelate reductase confers tolerance to growth on low iron and uncovers posttranscriptional control.

    PubMed

    Connolly, Erin L; Campbell, Nathan H; Grotz, Natasha; Prichard, Charis L; Guerinot, Mary Lou

    2003-11-01

    The Arabidopsis FRO2 gene encodes the low-iron-inducible ferric chelate reductase responsible for reduction of iron at the root surface. Here, we report that FRO2 and IRT1, the major transporter responsible for high-affinity iron uptake from the soil, are coordinately regulated at both the transcriptional and posttranscriptional levels. FRO2 and IRT1 are induced together following the imposition of iron starvation and are coordinately repressed following iron resupply. Steady-state mRNA levels of FRO2 and IRT1 are also coordinately regulated by zinc and cadmium. Like IRT1, FRO2 mRNA is detected in the epidermal cells of roots, consistent with its proposed role in iron uptake from the soil. FRO2 mRNA is detected at high levels in the roots and shoots of 35S-FRO2 transgenic plants. However, ferric chelate reductase activity is only elevated in the 35S-FRO2 plants under conditions of iron deficiency, indicating that FRO2 is subject to posttranscriptional regulation, as shown previously for IRT1. Finally, the 35S-FRO2 plants grow better on low iron as compared with wild-type plants, supporting the idea that reduction of ferric iron to ferrous iron is the rate-limiting step in iron uptake.

  1. Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron.

    PubMed

    Wang, Y-Q; Wang, M-Y; Fu, X-R; Peng-Yu; Gao, G-F; Fan, Y-M; Duan, X-L; Zhao, B-L; Chang, Y-Z; Shi, Z-H

    2015-01-01

    Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.

  2. Development of Iron-Chelating Poly(ethylene terephthalate) Packaging for Inhibiting Lipid Oxidation in Oil-in-Water Emulsions.

    PubMed

    Johnson, David R; Tian, Fang; Roman, Maxine J; Decker, Eric A; Goddard, Julie M

    2015-05-27

    Foods such as bulk oils, salad dressings, and nutritionally fortified beverages that are susceptible to oxidative degradation are often packaged in poly(ethylene terephthalate) (PET) bottles with metal chelators added to the food to maintain product quality. In the present work, a metal-chelating active packaging material is designed and characterized, in which poly(hydroxamic acid) (PHA) metal-chelating moieties were grafted from the surface of PET. Biomimetic PHA groups were grafted in a two-step UV-initiated process without the use of a photoinitiator. Surface characterization of the films by attenuated total reflective Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) suggested successful grafting and conversion of poly(hydroxyethyl acrylate) (PHEA) to PHA chelating moieties from the surface of PET. Colorimetric (ferrozine) and inductively coupled plasma mass spectroscopy (ICP-MS) assays demonstrated the ability of PET-g-PHA to chelate iron in a low-pH (3.0) environment containing a competitive metal chelator (citric acid). Lipid oxidation studies demonstrated the antioxidant activity of PET-g-PHA films in inhibiting iron-promoted oxidation in an acidified oil-in-water (O/W) emulsion model system (pH 3.0). Particle size and ζ-potential analysis indicated that the addition of PET-g-PHA films did not affect the physical stability of the emulsion system. This work suggests that biomimetic chelating moieties can be grafted from PET and effectively inhibit iron-promoted degradation reactions, enabling removal of metal-chelating additives from product formulations.

  3. 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.

    PubMed

    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.

  4. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    SciTech Connect

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K.

    1996-03-01

    The US Nuclear Regulatory Commission is responsible for regulating the safe land disposal of low-level radioactive wastes that may contain organic chelating agents. Such agents include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), picolinic acid, oxalic acid, and citric acid, and can form radionuclide-chelate complexes that may enhance the migration of radionuclides from disposal sites. Data from the available literature indicate that chelates can leach from solidified decontamination wastes in moderate concentration (1--100 ppm) and can potentially complex certain radionuclides in the leachates. In general it appears that both EDTA and DTPA have the potential to mobilize radionuclides from waste disposal sites because such chelates can leach in moderate concentration, form strong radionuclide-chelate complexes, and can be recalcitrant to biodegradation. It also appears that oxalic acid and citric acid will not greatly enhance the mobility of radionuclides from waste disposal sites because these chelates do not appear to leach in high concentration, tend to form relatively weak radionuclide-chelate complexes, and can be readily biodegraded. In the case of picolinic acid, insufficient data are available on adsorption, complexation of key radionuclides (such as the actinides), and biodegradation to make definitive predictions, although the available data indicate that picolinic acid can chelate certain radionuclides in the leachates.

  5. Preventive Therapy of Experimental Colitis with Selected iron Chelators and Anti-oxidants

    PubMed Central

    Minaiyan, Mohsen; Mostaghel, Elahe; Mahzouni, Parvin

    2012-01-01

    Objectives: Iron chelators, such as maltol and kojic acid, have antioxidant and anti-inflammatory properties. They may have beneficial effects on inflammatory bowel disease (IBD) because iron can develop and aggravate inflammation in IBD. In the present study, the effect of selected iron chelators and anti-oxidants were evaluated on a model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. Methods: Colitis was induced with instillation of 75 mg/kg TNBS in 0.25 ml ethanol 50% via the anus in fasted male Wistar rats. The animals were assigned randomly to 12 groups (n = 6) and treated once daily, started 2 hours before colitis induction, with normal saline (5 ml/kg), maltol (70, 140, 280 mg/kg), kojic acid (75, 150, 300 mg/kg), vitamin E (400 mg/kg), deferiprone (L1) (150 mg/kg) and prednisolone (4 mg/kg) orally and deferoxamine (50 mg/kg) intraperitoneally for 5 days. In the sixth day, rats were scarified and colon tissues were assessed macroscopically and pathologically. Results: Maltol (280 mg/kg) was able to reduce colon weight / length ratio, ulcer index and total colitis index similar to prednisolone, deferoxamine and deferiprone as positive controls. However, kojic acid and vitamin E could not significantly alleviate macroscopic and/or pathologic features of inflammation in comparison to normal saline. 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. PMID:22826760

  6. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major.

    PubMed

    Farmaki, Kallistheni; Tzoumari, Ioanna; Pappa, Christina; Chouliaras, Giorgos; Berdoukas, Vasilios

    2010-02-01

    Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients' iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.

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

    PubMed

    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 <1,250 μM had no effect, whereas DFP at 2,500 μM increased biofilms forming in A. fumigatus or preformed biofilms (P < 0.01). DFP at 156 to 2,500 μM inhibited biofilm formation (P < 0.01 to 0.001) in a dose-responsive manner. Biofilm formation with 625 μM DFP plus any concentration of FeCl3 was lower than that in the controls (P < 0.05 to 0.001). FeCl3 at ≥625 μM reversed the DFP inhibitory effect (P < 0.05 to 0.01), but the reversal was incomplete compared to the controls (P < 0.05 to 0.01). For preformed biofilms, DFP in the range of ≥625 to 1,250 μM was inhibitory compared to the controls (P < 0.01 to 0.001). FeCl3 at ≥625 μM overcame inhibition by 625 μM DFP (P < 0.001). FeCl3 alone at ≥156 μM stimulated biofilm formation (P < 0.05 to 0.001). Preformed A. fumigatus biofilm increased with 2,500 μM FeCl3 only (P < 0.05). In a strain survey, various susceptibilities of 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

  8. Characterization of the effect of serum and chelating agents on Staphylococcus aureus biofilm formation; chelating agents augment biofilm formation through clumping factor B

    NASA Astrophysics Data System (ADS)

    Abraham, Nabil Mathew

    Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and to investigate their effects on its capacity to form a biofilm. More specifically, the project investigated the effects of serum, and thereafter of catheter lock solutions on biofilm formation by S. aureus. Pre-coating polystyrene with serum is frequently used as a method to augment biofilm formation. The effect of pre-coating with serum is due to the deposition of extracellular matrix components onto the polystyrene, which are then recognized by MSCRAMMs. We therefore hypothesized that the major component of blood, serum, would induce biofilm formation. Surprisingly, serum actually inhibited biofilm formation. The inhibitory activity was due to a small molecular weight, heat-stable, non-proteinaceous component/s of serum. Serum-mediated inhibition of biofilm formation may represent a previously uncharacterized aspect of host innate immunity that targets the expression of a key bacterial virulence factor: the ability to establish a resistant biofilm. Metal ion chelators like sodium citrate are frequently chosen to lock intravenous catheters because they are regarded as potent inhibitors of bacterial biofilm formation and viability. We found that, while chelating compounds abolished biofilm formation in most strains of S. aureus, they actually augmented the phenotype in a subset of strains. We

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

    PubMed

    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+).

  10. Solubility and accumulation of metals in Chinese brake fern, vetiver and rostrate sesbania using chelating agents.

    PubMed

    Lou, L Q; Ye, Z H; Wong, M H

    2007-01-01

    Greenhouse experiments were conducted to study the effects of chelating agents on the growth and metal accumulation of Chinese brake fern (Pteris vittata L.), vetiver (Vetiveria zizanioides L.), and rostrate sesbania (Sesbania rostrata L.) in soil contaminated with arsenic (As), Cu, Pb, and Zn. Among the five chelating agents used [ethylenediaminetriacetic acid (EDTA), hydroxyethylenediaminetriacetic acid (HEDTA), nitrilotriacetic acid (NTA), oxalic acid (OA), and phytic acid (PA)], OA was the best to mobilize As, EDTA to mobilize Cu and Pb, and HEDTA to mobilize Zn from soil, respectively. The biomass of vetiver was the highest, followed by rostrate sesbania. All chelating agents inhibited the growth of Chinese brake fern and rostrate sesbania, but HEDTA significantly increased the aboveground biomass of vetiver. Dry weights of both Chinese brake fern and rostrate sesbania decreased with increasing EDTA concentrations amended in the soil, especially in treatments with high EDTA concentrations. EDTA and HEDTA enhanced Cu, Zn, and Pb, but lowered As accumulation in all three plant species, except for As in vetiver, while OA significantly enhanced As accumulation in the aboveground part of vetiver. Concentrations of Cu, Zn, and Pb in the aboveground parts of plants increased significantly with the increase of EDTA concentrations and treatment time. In addition to As, Chinese brake fern also accumulated the highest Cu, Pb, and Zn in its aboveground parts among the three plant species grown in metal-contaminated soil with EDTA/HEDTA treatments. This species, therefore, can be used to simultaneously clean up As, Cu, Pb, and Zn from contaminated soils with the aid of EDTA or HEDTA.

  11. Comparative evaluation of chelating agents on the mobilization of cadmium: A mechanistic approach

    SciTech Connect

    Srivastava, R.C.; Gupta, S.; Ahmad, N.

    1996-02-09

    A comparative evaluation of chelating agents, namely, diethyl dithiocarbamate (DDC), dimethyl dithiocarbamate (DMDC), 1,4,8,11-tetraazacyclotetradecane (CYCLAM), 1,4,8,12-tetraazacyclopentadecane (TACPD), 2,3-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propane sulfonate (DMPS) was conducted to assess their efficacy against acute cadmium (Cd) toxicity. DMSA and DMPS appeared to be most effective in reducing mortality as well as Cd burden of liver, kidneys, and brain in cadmium intoxicated mice. DMDC reduced Cd levels only in liver and kidneys, while DDC significantly enhanced its level in brain. CYCLAM and TACPD significantly increased the Cd level in liver and kidneys and were ineffective in brain. The therapeutic index as well as therapeutic efficacy was highest for DMSA followed by DMPS and DMDC. A fair degree of correlation was found to exist between (1) stability constant of Cd chelates and percent survival (r = .438), (2) stability constant and percent transport (r=.479), and (3) percent survival and percent transport (r = .447). However, the lipophilicity did not show any appreciable correlation with percent survival and stability constant of Cd chelates. 24 refs., 1 fig., 6 tabs.

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

    PubMed

    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.

  13. Siderochelin, a new ferrous-ion chelating agent produced by Nocardia.

    PubMed

    Liu, W C; Fisher, S M; Wells, J S; Ricca, C S; Principe, P A; Trejo, W H; Bonner, D P; Gougoutos, J Z; Toeplitz, B K; Sykes, R B

    1981-07-01

    A new ferrous-ion chelating agent, siderochelin, was isolated from fermentation broths of Nocardia sp. SC 11,340. Siderochelin was produced by conventional submerged culture and purified by solvent extraction and recrystallization. The antibiotic was crystallized from acetonitrile as a mixture of diastereoisomers. The molecular formula of siderochelin was determined as C11H13N3O3 on the basis of elemental analysis and mass spectrometry, and the structure was elucidated by X-ray crystallography. The compound shows a broad spectrum of antimicrobial activity, being active against bacteria, fungi and protozoa.

  14. Removing nitric oxide from flue gas using iron(II) citrate chelate absorption with microbial regeneration.

    PubMed

    Xu, Xinhua; Chang, Shih Ger

    2007-04-01

    The addition of metal chelates such as Fe(II)EDTA or Fe(II)Cit to wet flue gas desulfurization systems has been shown to increase the amount of NO(x) absorption from gas streams containing SO(2). This paper attempts to demonstrate the advantage of not only using Fe(II)Cit chelate to absorb nitrogen oxides from flue gas but also the advantage gained from adding microorganisms to the system. Two distinct classes of microorganisms are needed: denitrifying and iron-reducing bacteria. The presence of oxygen in flue gas will affect the absorption efficiency of NO by Fe(II)Cit chelate. The oxidation of Fe(II) can be slowed with the help of bacteria in two ways: bacteria can serve to directly reduce Fe(III) to Fe(II) or they can serve to keep levels of dissolved oxygen in the solution low. As a result, after NO absorption, Fe(II)(Cit)NO will be reduced by denitrifying bacteria to Fe(II)Cit while Fe(III) is reduced by anaerobic bacteria back to Fe(II). Our experiments have shown that the implementation of our protocol allowed for an NO reduction rate constant increase from standard levels of 0.0222-0.100 m Mh(-1) with inlet NO changed from 250 to 1000 ppm. We have also found that total Fe concentration tends to decrease after prolonged periods of operation due to the loss of some Fe to the formation of Fe(OH)(3) that settles together with the sludge at the bottom of bioreactor tank.

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

    PubMed Central

    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

  16. The iron chelator deferasirox induces apoptosis by targeting oncogenic Pyk2/β-catenin signaling in human multiple myeloma

    PubMed Central

    Sato, Tsutomu; Kawano, Yutaka; Murase, Kazuyuki; Arihara, Yohei; Kikuchi, Shohei; Hayasaka, Naotaka; Usami, Makoto; Iyama, Satoshi; Miyanishi, Koji; Sato, Yasushi; Kobune, Masayoshi; Kato, Junji

    2016-01-01

    Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling. PMID:27602957

  17. Improving the efficiency of phytoremediation using electrically charged plant and chelating agents.

    PubMed

    Tahmasbian, Iman; Safari Sinegani, Ali Akbar

    2016-02-01

    The low efficiency of phytoremediation is a considerable problem that limits the application of this environmentally friendly method on heavy metal-polluted soils. The combination of chelate-assisted phytoextraction and electrokinetic remediation could offer new opportunities to improve the effectiveness of phytoextraction. The current experiment aims to investigate the effects of electrical fields and chelating agents on phytoremediation efficiency. In a pot experiment using mine soil, poultry manure extract (PME), cow manure extract (CME), and ethylenediaminetetraacetic acid (EDTA) were applied to soil as chelating agents (2 g kg(-1)) at the beginning of the flowering stage. A week later, Helianthus annuus (sunflower) was negatively charged by inserting a stainless steel needle with 10 and 30 V DC electricity in the lowest part of the stems for 1 h each day for a 14-day period. At the end of the experiment, the shoot and root dry weight, lead (Pb) concentration in plant organs, translocation factor (TF), metal uptake index (UI), and soil available Pb (diethylene triamine pentaacetic acid (DTPA) extractable) were detected. Results indicated that the application of electrical fields had no significant impact on the shoot and root dry weights, while Pb concentration and UI increased in the 10-V EDTA treatment by 500 % compared to control. There was no significant difference between UI in 30- and 10-V EDTA treatments. Soil available Pb significantly increased in the 30-V treated soil. A positive correlation was observed between the available Pb in soil near the root and Pb concentration in shoot, its TF, and UI. In conclusion, a negatively charged plant along with the application of EDTA significantly increased the phytoremediation efficiency.

  18. Impact of iron chelators on short-term dissolution of basaltic glass

    NASA Astrophysics Data System (ADS)

    Perez, Anne; Rossano, Stéphanie; Trcera, Nicolas; Verney-Carron, Aurélie; Huguenot, David; van Hullebusch, Eric D.; Catillon, Gilles; Razafitianamaharavo, Angelina; Guyot, François

    2015-08-01

    Although microorganisms seem to play an important role in the alteration processes of basaltic glasses in solution, the elementary mechanisms involved remain unclear in particular with regard to the role of organic ligands excreted by the cells. Two glasses, one with Fe and one without Fe were synthesized to model basaltic glass compositions. Fe in the glass was mostly Fe(III) for enhancing interaction with siderophores, yet with small but significant amounts of Fe(II) (between 10% and 30% of iron). The prepared samples were submitted to abiotic alteration experiments in buffered (pH 6.4) diluted solutions of metal-specific ligands, namely oxalic acid (OA, 10 mM), desferrioxamine (DFA, 1 mM) or 2,2‧-bipyridyl (BPI, 1 mM). Element release from the glass into the solution after short term alteration (maximum 1 week) was measured by ICP-OES, and normalized mass losses and relative release ratios (with respect to Si) were evaluated for each element in each experimental condition. The presence of organic ligands had a significant effect on the dissolution of both glasses. Trivalent metals chelators (OA, DFA) impacted on the release of Fe3+ and Al3+, and thus on the global dissolution of both glasses, enhancing all release rates and dissolution stoichiometry (release rates were increased up to 7 times for Al or Fe). As expected, the mostly divalent metal chelator BPI interacted preferentially with Ca2+, Mg2+ and Fe2+. This study thus allows to highlight the central roles of iron and aluminium in interaction with some organic ligands in the alteration processes of basaltic glasses. It thus provides a step toward understanding the biological contribution of this fundamental geological process.

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

    PubMed

    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.

  20. Effect of a novel chelating agent on defect removal during post-CMP cleaning

    NASA Astrophysics Data System (ADS)

    Hong, Jiao; Niu, Xinhuan; Liu, Yuling; He, Yangang; Zhang, Baoguo; Wang, Juan; Han, Liying; Yan, Chenqi; Zhang, Jin

    2016-08-01

    Chemical mechanical polishing (CMP) has become widely accepted for the planarization of device interconnect structures in deep submicron semiconductor manufacturing. However, during CMP process the foreign particles, metal contaminants, and other chemical components are introduced onto the wafer surface, so CMP process is considered as one of the dirtiest process to wafer surface defects which may damage the GLSI patterns and the metallic impurities can induce many crystal defects in wafers during the following furnace processing. Therefore, the post-CMP cleaning of wafers has become a key step in successful CMP process and the polyvinyl alcohol (PVA) brush cleaning is the most effective method for post-CMP in situ cleaning. In this study, the effect of the chelating agent with different concentrations on defect removal by using PVA brush cleaning was discussed emphatically. It can be seen from the surface images obtained by scanning electron microscopy and KLA digital comparison system analysis confirmed that the chelating agent can effectively act on the defect removal.

  1. Chelating agents exert distinct effects on biofilm formation in Staphylococcus aureus depending on strain background: role for clumping factor B

    PubMed Central

    Abraham, Nabil M.; Lamlertthon, Supaporn; Fowler, Vance G.

    2012-01-01

    Staphylococcus aureus is a leading cause of catheter infections, and biofilm formation plays a key role in the pathogenesis. Metal ion chelators inhibit bacterial biofilm formation and viability, making them attractive candidates as components in catheter lock solutions. The goal of this study was to characterize further the effect of chelators on biofilm formation. The effect of the calcium chelators ethylene glycol tetraacetic acid (EGTA) and trisodium citrate (TSC) on biofilm formation by 30 S. aureus strains was tested. The response to subinhibitory doses of EGTA and TSC varied dramatically depending on strain variation. In some strains, the chelators prevented biofilm formation, in others they had no effect, and they actually enhanced biofilm formation in others. The molecular basis for this phenotypic variability was investigated using two related strains: Newman, in which biofilm formation was inhibited by chelators, and 10833, which formed strong biofilms in the presence of chelators. It was found that deletion of the gene encoding the surface adhesin clumping factor B (clfB) completely eliminated chelator-induced biofilm formation in strain 10833. The role of ClfB in biofilm formation activity in chelators was confirmed in additional strains. It was concluded that biofilm-forming ability varies strikingly depending on strain background, and that ClfB is involved in biofilm formation in the presence EGTA and citrate. These results suggest that subinhibitory doses of chelating agents in catheter lock solutions may actually augment biofilm formation in certain strains of S. aureus, and emphasize the importance of using these agents appropriately so that inhibitory doses are achieved consistently. PMID:22516131

  2. Phenyl-1-Pyridin-2yl-Ethanone-Based Iron Chelators Increase IκB-α Expression, Modulate CDK2 and CDK9 Activities, and Inhibit HIV-1 Transcription

    PubMed Central

    Kumari, Namita; Iordanskiy, Sergey; Kovalskyy, Dmytro; Breuer, Denitra; Niu, Xiaomei; Lin, Xionghao; Xu, Min; Gavrilenko, Konstantin; Kashanchi, Fatah; Dhawan, Subhash

    2014-01-01

    HIV-1 transcription is activated by the Tat protein, which recruits CDK9/cyclin T1 to the HIV-1 promoter. CDK9 is phosphorylated by CDK2, which facilitates formation of the high-molecular-weight positive transcription elongation factor b (P-TEFb) complex. We previously showed that chelation of intracellular iron inhibits CDK2 and CDK9 activities and suppresses HIV-1 transcription, but the mechanism of the inhibition was not understood. In the present study, we tested a set of novel iron chelators for the ability to inhibit HIV-1 transcription and elucidated their mechanism of action. Novel phenyl-1-pyridin-2yl-ethanone (PPY)-based iron chelators were synthesized and examined for their effects on cellular iron, HIV-1 inhibition, and cytotoxicity. Activities of CDK2 and CDK9, expression of CDK9-dependent and CDK2-inhibitory mRNAs, NF-κB expression, and HIV-1- and NF-κB-dependent transcription were determined. PPY-based iron chelators significantly inhibited HIV-1, with minimal cytotoxicity, in cultured and primary cells chronically or acutely infected with HIV-1 subtype B, but they had less of an effect on HIV-1 subtype C. Iron chelators upregulated the expression of IκB-α, with increased accumulation of cytoplasmic NF-κB. The iron chelators inhibited CDK2 activity and reduced the amount of CDK9/cyclin T1 in the large P-TEFb complex. Iron chelators reduced HIV-1 Gag and Env mRNA synthesis but had no effect on HIV-1 reverse transcription. In addition, iron chelators moderately inhibited basal HIV-1 transcription, equally affecting HIV-1 and Sp1- or NF-κB-driven transcription. By virtue of their involvement in targeting several key steps in HIV-1 transcription, these novel iron chelators have the potential for the development of new therapeutics for the treatment of HIV-1 infection. PMID:25155598

  3. Effect of age and caloric restriction on bleomycin-chelatable and nonheme iron in different tissues of C57BL/6 mice.

    PubMed

    Sohal, R S; Wennberg-Kirch, E; Jaiswal, K; Kwong, L K; Forster, M J

    1999-08-01

    The objective of this study was to test the hypothesis that the widely observed age-associated increase in the amounts of macromolecular oxidative damage is due to an elevation in the availability of redox-active iron, that is believed to catalyze the scission of H2O2 to generate the highly reactive hydroxyl radical. Concentrations of bleomycin-chelatable iron and nonheme iron were measured in various tissues and different regions of the brain of mice fed on ad libitum (AL) or a calorically restricted (to 60% of AL) diet at different ages. The concentrations of these two pools of iron varied markedly as a function of tissue, age, and caloric intake. There was no consistent ratio between the amounts of nonheme and the bleomycin-chelatable iron pools across these conditions. Nonheme iron concentration increased with age in the liver, kidney, heart, striatum, hippocampus, midbrain and cerebellum of AL animals, whereas bleomycin-chelatable iron increased significantly with age only in the liver. Amounts of both nonheme and bleomycin-chelatable iron remained unaltered during aging in the cerebral cortex and hindbrain of AL mice. Caloric restriction had no effect on iron concentration in the brain or heart, but caused a marked increase in the concentration of both bleomycin-chelatable and nonheme iron in the liver and the kidney. The results do not support the hypothesis that accumulation of oxidative damage with age, or its attenuation by CR, are associated with corresponding variations in redox-active iron.

  4. The effect of peroral administration of amino acid-chelated iron to pregnant sows in preventing sow and piglet anaemia.

    PubMed

    Egeli, A K; Framstad, T; Grønningen, D

    1998-01-01

    Two trials were performed in 2 different pig herds. In Trial 1, 9 pregnant Norwegian landrace sows were given a supplement in the feed of about 300 mg iron daily as amino acid-chelated iron (Bio-plex) during the last 3 weeks of gestation. Ten sows were included as controls. In Trial 2, 10 sows were fed a supplement of about 650 mg iron daily as glutamic acid-chelated iron (Super Fe-MAX) during the same period of pregnancy as in Trial 1. Twenty-two sows were included as controls. Blood samples were taken from the sows at the start of the experiment and on the day after parturition. The sows in Trial 1 were also bled at weaning 5 weeks after parturition. The piglets were weighted and blood samples collected 24 +/- 12 h after birth. Livers were taken from 65 piglets, which were either still-born or which died or were euthanised as one-day olds, and examined for iron content. The erythrocyte count (RBC), haemoglobin concentration (HGB), mean cell volume (MCV), erythrocyte distribution width (RDW), and haemoglobin distribution width (HDW) in blood were measured. Haematocrit (HCT), mean cell haemoglobin (MCH), and mean cell haemoglobin concentration (MCHC) were also estimated. Blood serum was analysed for total proteins, albumin, serum Fe, and total iron-binding capacity (TIBC). A slight increase in HGB and RBC in the piglets from the iron-treated sows compared with the controls was found in Trial 1, but this was considered to be of no practical importance. None of the other measured parameters were influenced by treating the pregnant sows with amino acid-chelated iron.

  5. Determination of ferric iron chelators by high-performance liquid chromatography using luminol chemiluminescence detection.

    PubMed

    Ariga, Tomoko; Imura, Yuki; Suzuki, Michio; Yoshimura, Etsuro

    2016-03-01

    Iron is an essential element for higher plants, and its acquisition and transportation is one of the greatest limiting factors for plant growth because of its low solubility in normal soil pHs. Higher plants biosynthesize ferric iron [Fe(III)] chelator (FIC), which solubilizes the iron and transports it to the rhizosphere. A high-performance liquid chromatography (HPLC) post-column method has been developed for the analysis of FICs using the luminol/H2O2 system for chemiluminescence (CL) detection. A size-exclusion column was the most suited in terms of column efficiency and CL detection efficiency. Mixing of the luminol with H2O2 in a post-column reaction was feasible, and a two-pump system was used to separately deliver the luminol and H2O2 solutions. The luminol and H2O2 concentrations were optimized using Fe(III)-EDTA and Fe(III)-citrate (Cit) solutions as analytes. A strong CL intensity was obtained for Fe(III)-Cit when EDTA was added to the luminol solution, probably because of an exchange of Cit with EDTA after separation on the HPLC column; CL efficiency was much higher for Fe(III)-EDTA than for Fe(III)-Cit with the luminol/H2O2 system. The present method can detect minute levels of Fe(III)-FICs; the detection limits of Fe(III)-EDTA, Fe(III)-Cit and Fe(III)-nicotianamine were 0.77, 2.3 and 1.1pmol, respectively.

  6. A Young Adult with Unintended Acute Intravenous Iron Intoxication Treated with Oral Chelation: The Use of Liver Ferriscan for Diagnosing and Monitoring Tissue Iron Load

    PubMed Central

    Yassin, Mohamed; Soliman, Ashraf T; De Sanctis, Vincenzo; Moustafa, Abbas; Samaan, Sandra Abou; Nashwan, Abdulqadir

    2017-01-01

    Acute iron intoxication (FeI) in humans has not been adequately studied. The manifestation of FeI, defined as a serum iron concentration >300 μg/dL (55 μmol/L) within 12 hours of ingestion, include various symptoms appearing in progressive stages. Systemic toxicity is expected with an intake of 60 mg/kg. A 27-year-old female nurse presented with unintended acute intravenous iron intoxication (FeI) a week after self-injecting herself with 20 ampoules of IV iron (4,000 mg elemental iron, 60 mg/kg). She had stable vital signs and mild hepatic tenderness. Hepatic MRI (Ferriscan®) showed a moderate/severe liver iron content (LIC: 9 mg/g dry tissue). Her hemogram, electrolytes, hepatic and renal functions were normal. Based on the high dose of iron received and her elevated LIC, chelation therapy was advised. She accepted only oral therapy and was started on deferasirox at a dose of 30 mg/kg daily. This oral chelation proved to be effective in clearing her hepatic iron overload after six months (LIC: 2 mg/g dry tissue), without side effects. This case also proved the value of Ferriscan® in diagnosing the degree of hepatic FeI and monitoring therapy to achieve a safe level of LIC. PMID:28101313

  7. The use of chelating agents in the remediation of metal-contaminated soils: a review.

    PubMed

    Lestan, Domen; Luo, Chun-ling; Li, Xiang-dong

    2008-05-01

    This paper reviews current remediation technologies that use chelating agents for the mobilization and removal of potentially toxic metals from contaminated soils. These processes can be done in situ as enhanced phytoextraction, chelant enhanced electrokinetic extraction and soil flushing, or ex situ as the extraction of soil slurry and soil heap/column leaching. Current proposals on how to treat and recycle waste washing solutions after soil is washed are discussed. The major controlling factors in phytoextraction and possible strategies for reducing the leaching of metals associated with the application of chelants are also reviewed. Finally, the possible impact of abiotic and biotic soil factors on the toxicity of metals left after the washing of soil and enhanced phytoextraction are briefly addressed.

  8. Iron Oxide as an MRI Contrast Agent for Cell Tracking

    PubMed Central

    Korchinski, Daniel J.; Taha, May; Yang, Runze; Nathoo, Nabeela; Dunn, Jeff F.

    2015-01-01

    Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation. PMID:26483609

  9. Caustic Leaching of SRS Tank 12H Sludge With and Without Chelating Agents

    SciTech Connect

    Spencer, B.B.

    2003-04-30

    The primary objective of this study was to measure the effect of adding triethanolamine (TEA) to caustic leaching solutions to improve the solubility of aluminum in actual tank-waste sludge. High-level radioactive waste sludge that had a high aluminum assay was used for the tests. This waste, which originated with the processing of aluminum-clad/aluminum-alloy fuels, generates high levels of heat because of the high {sup 90}Sr concentration and contains hard-to-dissolve boehmite phases. In concept, a chelating agent, such as TEA, can both improve the dissolution rate and increase the concentration in the liquid phase. For this reason, TEA could also increase the solubility of other sludge components that are potentially problematic to downstream processing. Tests were conducted to determine if this were the case. Because of its relatively high vapor pressure, process design should include methods to minimize losses of the TEA. Sludge was retrieved from tank 12H at the Savannah River Site by on-site personnel, and then shipped to Oak Ridge National Laboratory for the study. The sludge contained a small quantity of rocky debris. One slate-like flat piece, which had approximate dimensions of 1 1/4 x 1/2 x 1/8 in., was recovered. Additional gravel-like fragments with approximate diameters ranging from 1/8 to 1/4 in. were also recovered by sieving the sludge slurry through a 1.4-mm square-pitch stainless steel mesh. These particles ranged from a yellow quartz-like material to grey-colored gravel. Of the 32.50 g of sludge received, the mass of the debris was only 0.89 g, and the finely divided sludge comprised {approx}97% of the mass. The sludge was successfully subdivided into uniform aliquots during hot-cell operations. Analytical measurements confirmed the uniformity of the samples. The smaller sludge samples were then used as needed for leaching experiments conducted in a glove box. Six tests were performed with leachate concentrations ranging from 0.1 to 3.0 m Na

  10. Comparison of food antioxidants and iron chelators in two cellular free radical assays: strong protection by luteolin.

    PubMed

    Hofer, Tim; Jørgensen, Trond Ø; Olsen, Ragnar L

    2014-08-20

    Liver (HepG2) cells were incubated with 21 edible flavonoids, carotenoids, polyunsaturated fatty acid (PUFA) chromones, and metal chelators for 1 h, washed in PBS, and challenged in the cellular antioxidant activity (CAA) and the cellular lipid peroxidation antioxidant activity (CLPAA) assays. These microplate format assays assess the compounds' ability to protect against cytosolic peroxyl radicals (CAA) and induced membrane lipid peroxidation (CLPAA), respectively. Incubation encompassing a broad compound concentration range determined half-maximal inhibitory concentrations (IC(50)) by using sigmoidal curve fits. Overall, considering both assays, luteolin offered the greatest protection. The carotenoid astaxanthin offered only modest protection, whereas β-carotene was ineffective. Subtle structural differences between flavonoids were found to have amplified effects on protective abilities, and mechanisms of flavonoid antioxidant action are discussed. Membrane-permeable iron chelators (deferasirox and SIH) offered strong protective effects in CLPAA, but not in CAA, suggesting that CLPAA is dependent on membrane-associated free iron ions.

  11. Transient Proteotoxicity of Bacterial Virulence Factor Pyocyanin in Renal Tubular Epithelial Cells Induces ER-Related Vacuolation and Can Be Efficiently Modulated by Iron Chelators

    PubMed Central

    Mossine, Valeri V.; Waters, James K.; Chance, Deborah L.; Mawhinney, Thomas P.

    2016-01-01

    Persistent infections of biofilm forming bacteria, such as Pseudomonas aeruginosa, are common among human populations, due to the bacterial resistance to antibiotics and other adaptation strategies, including release of cytotoxic virulent factors such as pigment pyocyanin (PCN). Urinary tract infections harbor P. aeruginosa strains characterized by the highest PCN-producing capacity, yet no information is available on PCN cytotoxicity mechanism in kidney. We report here that renal tubular epithelial cell (RTEC) line NRK-52E responds to PCN treatments with paraptosis-like activity features. Specifically, PCN-treated cells experienced dilation of endoplasmic reticulum (ER) and an extensive development of ER-derived vacuoles after about 8 h. This process was accompanied with hyper-activation of proteotoxic stress-inducible transcription factors Nrf2, ATF6, and HSF-1. The cells could be rescued by withdrawal of PCN from the culture media before the vacuoles burst and cells die of non-programmed necrosis after about 24–30 h. The paraptosis-like activity was abrogated by co-treatment of the cells with metal-chelating antioxidants. A microscopic examination of cells co-treated with PCN and agents aiming at a variety of the cellular stress mediators and pathways have identified iron as a single most significant co-factor of the PCN cytotoxicity in the RTECs. Among biologically relevant metal ions, low micromolar Fe2+ specifically mediated anaerobic oxidation of glutathione by PCN, but catechol derivatives and other strong iron complexing agents could inhibit the reaction. Our data suggest that iron chelation could be considered as a supplementary treatment in the PCN-positive infections. PMID:27613716

  12. Thumbnail Sketches: EDTA-Type Chelating Agents in Everyday Consumer Products: Some Food, Cleaning, and Photographic Applications.

    ERIC Educational Resources Information Center

    Hart, J. Roger

    1985-01-01

    Discusses the role of chelating agents in (1) mayonnaise and salad dressings; (2) canned legumes; (3) plant foods; (4) liquid dishwashing detergents; (5) toilet soaps; (6) floor wax removers; (7) hard surface cleaners; (8) carpet cleaning; (9) bathtub and tile cleaners; and (10) photography. (JN)

  13. Mechanism of sorption sulpho-derivative organic chelating agents on strong base anion exchanger Amberlite IRA-402 by FT-IR/PAS and DRS methods

    NASA Astrophysics Data System (ADS)

    Wronski, G.; Pasieczna-Patkowska, S.; Hubicki, Z.

    2008-02-01

    In the paper, strong base anion exchanger Amberlite IRA-402 was modified by using sulpho-derivative organic chelating agents as: Brilliant Yellow, Xylenol Orange, Bromophenyl Blue. The investigations exhibited, that anion exchanger Amberlite IRA-402 is modified very simply by organic chelating agents (working capacity 0.25 0.5 g/cm3).

  14. Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells.

    PubMed

    Nishigaki, Ikuo; Rajendran, Peramaiyan; Venugopal, Ramachandran; Ekambaram, Gnapathy; Sakthisekaran, Dhanapal; Nishigaki, Yutaka

    2010-01-01

    Astaxanthin (ASX), a red carotenoid pigment with no pro-vitamin A activity, is a biological antioxidant that occurs naturally in a wide variety of plants, algae and seafoods. This study investigated whether ASX could inhibit glycated protein/iron chelate-induced toxicity in human umbilical-vein endothelial cells (HUVEC) by interfering with ROS generation in these cells. Glycated fetal bovine serum (GFBS) was prepared by incubating fetal bovine serum (FBS) with high-concentration glucose. Stimulation of cultured HUVECs with 50 mm 1 mL of GFBS significantly enhanced lipid peroxidation and decreased antioxidant enzyme activities and levels of phase II enzymes. However, preincubation of the cultures with ASX resulted in a marked decrease in the level of lipid peroxide (LPO) and an increase in the levels of antioxidant enzymes in an ASX concentration-dependent manner. These results demonstrate that ASX could inhibit LPO formation and enhance the antioxidant enzyme status in GFBS/iron chelate-exposed endothelial cells by suppressing ROS generation, thereby limiting the effects of the AGE-RAGE interaction. The results indicate that ASX could have a beneficial role against glycated protein/iron chelate-induced toxicity by preventing lipid and protein oxidation and increasing the activity of antioxidant enzymes.

  15. The Exochelins of Pathogenic Mycobacteria: Unique, Highly Potent, Lipid- and Water-Soluble Hexadentate Iron Chelators with Multiple Potential Therapeutic Uses

    PubMed Central

    Horwitz, Lawrence D.

    2014-01-01

    Abstract Significance: Exochelins are lipid- and water-soluble siderophores of Mycobacterium tuberculosis with unique properties that endow them with exceptional pharmacologic utility. Exochelins can be utilized as probes to decipher the role of iron in normal and pathological states, and, since they rapidly cross cell membranes and chelate intracellular iron with little or no toxicity, exochelins are potentially useful for the treatment of a number of iron-dependent pathological phenomena. Recent Advances: In animal models, exochelins have been demonstrated to have promise for the treatment of transfusion-related iron overload, restenosis after coronary artery angioplasty, cancer, and oxidative injury associated with acute myocardial infarction and transplantation. Critical Issues: To be clinically effective, iron chelators should be able to rapidly enter cells and chelate iron at key intracellular sites. Desferri-exochelins, and other lipid-soluble chelators, can readily cross cell membranes and remove intracellular free iron; whereas deferoxamine, which is lipid insoluble, cannot do so. Clinical utility also requires that the chelators be nontoxic, which, we hypothesize, includes the capability to prevent iron from catalyzing free radical reactions which produce •OH or other reactive oxygen species. Lipid-soluble iron chelators currently available for clinical application are bidentate (deferiprone) or tridentate (desferasirox) molecules that do not block all six sites on the iron molecule capable of catalyzing free radical reactions. In contrast, desferri-exochelins are hexadentate molecules, and by forming a one-to-one binding relationship with iron, they prevent free radical reactions. Future Directions: Clinical studies are needed to assess the utility of desferri-exochelins in the treatment of iron-dependent pathological disorders. Antioxid. Redox Signal. 21, 2246–2261. PMID:24684595

  16. Competitive binding of Pu and Am with bone mineral and novel chelating agents.

    PubMed

    Guilmette, R A; Hakimi, R; Durbin, P W; Xu, J; Raymond, K N

    2003-01-01

    Effective direct removal of actinides such as Pu and Am from bone in vivo has not been accomplished to date, even with the strong chelating agents CaNa3DTPA or ZnNa3DTPA. This study, using an established in vitro system, compared removal of Pu and Am bound to bone mineral by ZnNa3DTPA and 10 chelating agents designed specifically to sequester actinides, including Pu and Am. Ligands tested were tetra, hexa, and octadentate, with linear or branched backbones containing sulfocatechol [CAM(S)], hydroxycatechol [CAM(C)], hydroxipyridinone (1,2-HOPO, Me-3,2-HOPO), or hydroxamate functional groups. The wide range of Pu and Am removal exhibited by the test ligands generally agreed with their metal coordination and chemical properties. The most effective agents for Pu (100 microM concentration, 24-48 h contact) are all octadentate as follows: 3,4,3-LICAM(S) (54% unbound); 3,4,3-LICAM(C) (6.2%); 3,4,3-LI(1,2-HOPO) (3.8%); H(2,2)-(Me-3,2-HOPO) (2.2%) and DFO-(1,2-HOPO) (1.8%). The other ligands removed less than 1% of the bound Pu; and ZnNa3DTPA removed only 0.086%. The most effective ligands for Am removal (100 microM, 24-48 h contact) are as follows: octadentate H(2,2)-(Me-3,2-HOPO) (21% unbound); 3,4,3-LI(1,2-HOPO) (14.5%) and 3,4,3-LICAM(C) (5.9%); hexadentate TREN-(Me-3,2-HOPO) and TREN-(1,2-HOPO) (9.6%); and tetradentate 5-LIO(Me-3,2-HOPO) (5.2%). Am removal by ZnNa3DTPA was about 1.4%. Among the ligands presently considered for possible human use, only 3,4,3-LI(1,2-HOPO) removed potentially useful amounts of both Pu and Am from bone mineral.

  17. Competitive binding of plutonium and americium with bone mineral and novel chelating agents

    SciTech Connect

    Guilmette, Ray A.; Hakimi, R.; Durbin, P. W.; Xu, J.; Raymond, K. N.

    2002-01-01

    Effective direct removal of actinides such as Pu and Am from bone in vivo has not been accomplished to date, even with the strong chelating agents CaNa{sub 3}DTPA or ZnNa{sub 3}DTPA. This study, using an established in vitro system, compared removal of Pu and Am bound to bone mineral by ZnNa{sub 3}DTPA and 10 chelating agents designed specifically to sequester actinides, including Pu and Am. Ligands tested were tetra-, hexa, and octadentate with linear or branched backbones containing sulfocatechol [CAM(S)], hydroxycatechol [CAM(C)], hydroxipyridinone (1,2-HOPO, Me-3,2-HOPO), or hydroxamate functional groups. The wide range of Pu and Am removal exhibited by the test ligands generally agreed with their metal coordination and chemical properties. The most effective agents for Pu (100 {micro}M concentration, 24-48 h contact) are all octadentate as follows: 3,4,3-LICAM(S) (54% unbound), 3,4,3-LICAM(C) (6.2%), 3,4,3-LI(1,2-HOPO) (3.8%), H(2,2)-(Me-3,2-HOPO) (2.2%) and DFO-(1,2-HOPO) (1.8%). The other ligands removed less than 1% of the bound Pu, and ZnNa{sub 3}DTPA removed only 0.086%. The most effective ligands for Am removal (100 {micro}M, 24-48 h contact) are as follows: octadentate H(2,2)-(Me-3,2-HOPO) (21% unbound), 3,4,3-LI(1,2-HOPO) (14.5%), and 3,4,3-LICAM(C) (5.9%), hexadentate TREN-(Me-3,2-HOPO) and TREN-(1,2-HOPO) (9.6%), and tetradentate 5-LIO(Me-3,2-HOPO) (5.2%). Am removal by ZnNa{sub 3}DTPA was about 1.4%. Among the ligands presently considered for possible human use, only 3,4,3-LI(1,2-HOPO) removed potentially useful amounts of both Pu and Am from bone mineral.

  18. Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

    PubMed

    Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

    2014-10-01

    Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity.

  19. Favorable pendant-amino metal chelation in VX nerve agent model systems.

    PubMed

    Bandyopadhyay, Indrajit; Kim, Min Jeong; Lee, Yoon Sup; Churchill, David G

    2006-03-16

    We have performed DFT computational studies [B3LYP, 6-31+G] to obtain metal ion coordination isomers of VX-Me [MeP(O)(OMe)(SCH2CH2NMe2)], a model of two of the most lethal nerve agents: VX [MeP(O)(OEt)(SCH2CH2N(iPr)2)] and Russian-VX [MeP(O)(OCH2CHMe2)(SCH2CH2N(Et)2)]. Our calculations involved geometry optimizations of the neutral VX-Me model as well as complexes with H+, Li+, Na+, K+, Be2+, Mg2+, and Ca2+ that yielded 2-8 different stable chelation modes for each ion that involved mainly mono- and bidentate binding. Importantly, our studies revealed that the [O(P),N] bidentate binding mode, long thought to be the active mode in differentiating the hydrolytic path of VX from other nerve agents, was the most stable for all ions studied here. Binding energy depended mainly on ionic size as well as charge, with binding energies ranging from 364 kcal mol(-1) for Be2+ to 33 kcal mol(-1) for K+. Furthermore, calculated NMR shifts for VX-Me correlate to experimental values of VX.

  20. Chemical and biological properties of toxic metals and use of chelating agents for the pharmacological treatment of metal poisoning.

    PubMed

    Sinicropi, Maria Stefania; Amantea, Diana; Caruso, Anna; Saturnino, Carmela

    2010-07-01

    Exposure to toxic metals is a well-known problem in industrialized countries. Metals interfere with a number of physiological processes, including central nervous system (CNS), haematopoietic, hepatic and renal functions. In the evaluation of the toxicity of a particular metal it is crucial to consider many parameters: chemical forms (elemental, organic or inorganic), binding capability, presence of specific proteins that selectively bind metals, etc. Medical treatment of acute and chronic metal toxicity is provided by chelating agents, namely organic compounds capable of interacting with metal ions to form structures called chelates. The present review attempts to provide updated information about the mechanisms, the cellular targets and the effects of toxic metals.

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

    PubMed

    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.

  2. Determination of o,oEDDHA - a xenobiotic chelating agent used in Fe fertilizers - in plant tissues by liquid chromatography/electrospray mass spectrometry: overcoming matrix effects.

    PubMed

    Orera, Irene; Abadía, Anunciación; Abadía, Javier; Alvarez-Fernández, Ana

    2009-06-01

    The Fe(III)-chelate of ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid (o,oEDDHA) is generally considered as the most efficient and widespread Fe fertilizer for fruit crops and intensive horticulture. The determination of the xenobiotic chelating agent o,oEDDHA inside the plant is a key issue in the study of this fertilizer. Both the low concentrations of o,oEDDHA expected and the complexity of plant matrices have been important drawbacks in the development of analytical methods for the determination of o,oEDDHA in plant tissues. The determination of o,oEDDHA in plant materials has been tackled in this study by liquid chromatography coupled to mass spectrometry using several plant species and tissues. Two types of internal standards have been tested: Iron stable isotope labeled compounds and a structural analogue compound, the Fe(III) chelate of ethylenediamine-N,N'-bis(2-hydroxy-4-methylphenylacetic) acid (o,oEDDHMA). Iron stable isotope labeled internal standards did not appear to be suitable because of the occurrence of isobaric endogenous compounds and/or isotope exchange reactions between plant native Fe pools and the Fe stable isotope of the internal standard. However, the structural analogue Fe(III)-o,oEDDHMA is an adequate internal standard for the determination of both isomers of o,oEDDHA (racemic and meso) in plant tissues. The method was highly sensitive, with limits of detection and quantification in the range of 3-49 and 11-162 pmol g(-1) fresh weight, respectively, and analyte recoveries were in the range of 74-116%. Using this methodology, both o,oEDDHA isomers were found in all tissues of sugar beet and tomato plants treated with 90 microM Fe(III)-o,oEDDHA for 24 h, including leaves, roots and xylem sap. This methodology constitutes a useful tool for studies on o,oEDDHA plant uptake, transport and allocation.

  3. [Influence of ionizing radiation, application of iron ions and their chelate complexes on the oxidative status of blood serum of rats].

    PubMed

    Riabchenko, N I; Ivannik, B P; Riabchenko, V I; Dzikovskaia, L A

    2011-01-01

    Influence of ionizing radiation, ions of iron and their chelate complexes on the oxidative status of blood serum of rats has been investigated. Animals were irradiated by gamma-rays 60Co at a dose of 4 Gy. Ions of iron and iron chelates with nitrilotriacetic acid and citric acid were introduced into animals intra-abdominally at a doze of 10 mg of iron on 1 kg of body weight. The oxidative status of blood serum was determined according to the estimated content of oxidizing peroxide equivalents which oxidize ferrous iron in ferric iron with the subsequent estimation of ferric iron by means of xylenol orange. We also estimated the total content of iron in blood serum using ferrozine as an indicator. The oxidative status was defined 24 and 96 hours after irradiation and 2 hours after introduction of iron ions and their chelates. The research conducted has shown that the concentration of oxidizing peroxide equivalents in serum and the total iron concentration increase 1.47 times and 1.63 times correspondingly 24 hours after irradiation. The increase in the content of oxidizing peroxide equivalents and iron owing to Fenton's reaction can lead to the appearance of OH* radical and raise the level of damage of nuclear and membrane structures in irradiated cells. 2 hours after introduction of iron ions and their chelates, the content of oxidizing peroxide equivalents increased in the blood serum of irradiated and non-irradiated rats, and the maximum effect was observed when introducing ferrous iron and its chelate with citric acid.

  4. Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila.

    PubMed Central

    Byrd, T F; Horwitz, M A

    1991-01-01

    We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon

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

    PubMed

    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).

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

    PubMed Central

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

    2012-01-01

    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-order rate constants for DNAsupercoiled to DNAnicked conversion up to 2.5 ×106 M-1min-1, and for DNAnicked to DNAlinear up to 7 ×105 M-1min-1. Relative rates of radical generation and characterization of radical species were determined by reaction with the fluorescent radical probe TEMPO-9-AC and rhodamine B. Ascorbate turnover rate constants ranging from 9.1×10-3 to 8.2 min-1 were determined, although many complexes demonstrated no measureable activity. Inhibition and Freifelder-Trumbo analysis of DNA cleavage supported concerted cleavage of dsDNA by a metal associated ROS in the case of Cu2+(aq), Cu-KGHK, Co-KGHK, and Cu-NTA and stepwise cleavage for Fe2+(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 mV to +1111 mV versus NHE, and complexes demonstrated optimal catalytic activity in the range of the physiological redox coreactants ascorbate and peroxide (-66 to +380 mV). PMID:21815680

  7. Optimization of isolation of cellulose from orange peel using sodium hydroxide and chelating agents.

    PubMed

    Bicu, Ioan; Mustata, Fanica

    2013-10-15

    Response surface methodology was used to optimize cellulose recovery from orange peel using sodium hydroxide (NaOH) as isolation reagent, and to minimize its ash content using ethylenediaminetetraacetic acid (EDTA) as chelating agent. The independent variables were NaOH charge, EDTA charge and cooking time. Other two constant parameters were cooking temperature (98 °C) and liquid-to-solid ratio (7.5). The dependent variables were cellulose yield and ash content. A second-order polynomial model was used for plotting response surfaces and for determining optimum cooking conditions. The analysis of coefficient values for independent variables in the regression equation showed that NaOH and EDTA charges were major factors influencing the cellulose yield and ash content, respectively. Optimum conditions were defined by: NaOH charge 38.2%, EDTA charge 9.56%, and cooking time 317 min. The predicted cellulose yield was 24.06% and ash content 0.69%. A good agreement between the experimental values and the predicted was observed.

  8. Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

    DOEpatents

    Katti, Kattesh V.; Gali, Hariprasad; Volkert, Wynn A.

    2004-08-24

    This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P.sup.III centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

  9. Universal dispersing agent for electrophoretic deposition of inorganic materials with improved adsorption, triggered by chelating monomers.

    PubMed

    Liu, Yangshuai; Luo, Dan; Ata, Mustafa S; Zhang, Tianshi; Wallar, Cameron J; Zhitomirsky, Igor

    2016-01-15

    Poly[1-[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) is a polymeric functional material with a number of unique physical properties, which attracted significant interest of different scientific communities. Films of PAZO were deposited by anodic electrophoretic deposition (EPD) under constant current and constant voltage conditions. The deposition kinetics was analyzed under different conditions and the deposition mechanism was discussed. New strategy was developed for the EPD of different inorganic materials and composites using PAZO as a dispersing, charging, binding and film forming agent. It was found that PAZO exhibits remarkable adsorption on various inorganic materials due to the presence of chelating salicylate ligands in its molecular structure. The salicylate ligands of PAZO monomers provide multiple adsorption sites by complexation of metal atoms on particle surfaces and allow for efficient electrosteric stabilization of particle suspensions. The remarkable performance of PAZO in its application in EPD have been exemplified by deposition of a wide variety of inorganic materials including the single element oxides (NiO, ZnO, Fe2O3) the complex oxides (Al2TiO5, BaTiO3, ZrSiO4, CoFe2O4) different nitrides (TiN, Si3N4, BN) as well as pure Ni metal and hydrotalcite clay. The use of PAZO can avoid limitation of other dispersing agents in deposition and co-deposition of different materials. Composite films were obtained using PAZO as a co-dispersant for different inorganic materials. The deposit composition, microstructure and deposition yield can be varied. The EPD method offers the advantages of simplicity, high deposition rate, and ability to deposit thin or thick films.

  10. From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents.

    PubMed

    An, Dahlia D; Kullgren, Birgitta; Jarvis, Erin E; Abergel, Rebecca J

    2017-04-01

    The potential consequences of a major radiological event are not only large-scale external radiation exposure of the population, but also uncontrolled dissemination of, and internal contamination with, radionuclides. When planning an emergency response to radiological and nuclear incidents, one must consider the need for not only post-exposure treatment for contaminated individuals, but also prophylactic measures to protect the workforce facing contaminated areas and patients in the aftermath of such events. In addition to meeting the desired criteria for post-exposure treatments such as safety, ease of administration, and broad-spectrum efficacy against multiple radionuclides and levels of challenge, ideal prophylactic countermeasures must include rapid onset; induce minimal to no performance-decrementing side effects; be compatible with current military Chemical, Biological, Radiological, Nuclear, and Explosive countermeasures; and require minimal logistical burdens. Hydroxypyridinone-based actinide decorporation agents have shown the most promise as decorporation strategies for various radionuclides of concern, including the actinides plutonium and americium. The studies presented here probe the extent of plutonium decorporation efficacy for two chelating agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), from early pre-exposure time points to a delay of up to 7 days in parenteral or oral treatment administration, i.e., well beyond the initial hours of emergency response. Despite delayed treatment after a contamination event, both ligands clearly enhanced plutonium elimination through the investigated 7-day post-treatment period. In addition, a remarkable prophylactic efficacy was revealed for 3,4,3-LI(1,2-HOPO) with treatment as early as 48 h before the plutonium challenge. This work provides new perspectives in the indication and use of experimental actinide decorporation treatments.

  11. Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.

    PubMed

    Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B; Kalinowski, Danuta S; Lovejoy, David B; Lane, Darius J R; Richardson, Des R

    2013-12-01

    Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.

  12. An Intracellular Iron Chelator Pleiotropically Suppresses Enzymatic and Growth Defects of Superoxide Dismutase-Deficient Escherichia coli

    PubMed Central

    Maringanti, Sujatha; Imlay, James A.

    1999-01-01

    Mutants of Escherichia coli that lack cytoplasmic superoxide dismutase (SOD) exhibit auxotrophies for sulfur-containing, branched-chain, and aromatic amino acids and cannot catabolize nonfermentable carbon sources. A secondary-site mutation substantially relieved all of these growth defects. The requirement for fermentable carbon and the branched-chain auxotrophy occur because superoxide (O2−) leaches iron from the [4Fe-4S] clusters of a family of dehydratases, thereby inactivating them; the suppression of these phenotypes was mediated by the restoration of activity to these dehydratases, evidently without changing the intracellular concentration of O2−. Cloning, complementation, and sequence analysis identified the suppressor mutation to be in dapD, which encodes tetrahydrodipicolinate succinylase, an enzyme involved in diaminopimelate and lysine biosynthesis. A block in dapB, which encodes dihydrodipicolinate reductase in the same pathway, conferred similar protection. Genetic analysis indicated that the protection stems from the intracellular accumulation of tetrahydro- or dihydrodipicolinate. Heterologous expression in the SOD mutants of the dipicolinate synthase of Bacillus subtilis generated dipicolinate and similarly protected them. Dipicolinates are excellent iron chelators, and their accumulation in the cell triggered derepression of the Fur regulon and a large increase in the intracellular pool of free iron, presumably as a dipicolinate chelate. A fur mutation only partially relieved the auxotrophies, indicating that Fur derepression assists but is not sufficient for suppression. It seems plausible that the abundant internal iron permits efficient reactivation of superoxide-damaged iron-sulfur clusters. This result provides circumstantial evidence that the sulfur and aromatic auxotrophies of SOD mutants are also directly or indirectly linked to iron metabolism. PMID:10368155

  13. Health-Related Quality of Life and Health Utility Values in Beta Thalassemia Major Patients Receiving Different Types of Iron Chelators in Iran

    PubMed Central

    Seyedifar, Meysam; Dorkoosh, Farid Abedin; Hamidieh, Amir Ali; Naderi, Majid; Karami, Hossein; Karimi, Mehran; Fadaiyrayeny, Masoomeh; Musavi, Masoumeh; Safaei, Sanaz; Ahmadian-Attari, Mohammad Mahdi; Hadjibabaie, Molouk; Cheraghali, Abdol Majid; Akbari Sari, Ali

    2016-01-01

    Background: Thalassemia is a chronic, inherited blood disorder, which in its most severe form, causes life-threatening anemia. Thalassemia patients not only engage with difficulties of blood transfusion and iron chelating therapy but also have some social challenges and health threatening factors. There are some reports on quality of life in thalassemia patients around the world from southeast of Asia to Italy in Europe and United States. In this study, we tried to evaluate and compare Health Related Quality of life (HRQoL) and the health utility in beta thalassemia major patients receiving different types of iron chelators and living in different socio-economical situations. Subjects and Methods: EQ-5D-3L accompanied by a Visual Analogue Scale (VAS) questionnaire was used. The respondents were patients with beta thalassemia major that were at least 12 years old selected from 3 provinces of Sistan-Blouchestan, Fars and Mazandaran. Comorbidities including heart complication, Diabetes Mellitus and Hepatitis and also types of iron chelators (oral, injection, combination of both) were also asked. Cross tab and ANOVA analysis conducted to evaluate each dimension score and health utility differences between provinces, iron chelation methods, comorbidities, age group and gender. Results: 528 patients answered the questionnaires. The health utility of patients that received oral iron chelator were 0.87 ± .01 for oral iron chelators versus 0.81 ± .01 for injection dosage form (p<0.05). Increase in age was accompanied by decrease in health utility. Females faced more usual activity problems, anxiety and depression. Heart problems were more prevalent in males. Conclusion: This study suggests that the quality of life of beta thalassemia major patients is dependent on type of iron chelation treatment which they received, the gender they have, the comorbidities they suffer and socio-economical situations they live in. PMID:27928477

  14. Heterogeneity of myocardial iron distribution in response to chelation therapy in patients with transfusion-dependent anemias.

    PubMed

    Hanneman, Kate; Raju, Vikram M; Moshonov, Hadas; Ward, Richard; Wintersperger, Bernd J; Crean, Andrew M; Ross, Heather; Nguyen, Elsie T

    2013-10-01

    The purpose of this study is to examine the effect of different iron chelation regimens on the distribution of myocardial iron in patients with transfusion-dependent anemias. Institutional review board approval was obtained. Patients treated with iron chelation therapy who had undergone baseline and 1-year follow-up cardiac T2* MR studies in a four-year period were identified retrospectively. One hundred and eight patients (44 % male, mean age 31.6 ± 9.7 years) were included. The interventricular septum on three short-axis slices (basal, mid and apical) was divided into anterior and inferior regions of interest for T2* analysis. Cardiac iron concentration (CIC) was calculated from T2* values. Statistical analysis included analysis of variance and paired t-test, using Bonferroni adjustment in all pairwise comparisons. At baseline, T2* measurements varied significantly across all six regions (p < 0.001): lowest in the mid anteroseptum (mean 22.3 ± 10.1 ms) and highest in the apical inferoseptum (mean 26.2 ± 12.8 ms). At follow-up, T2* and CIC values improved significantly in all segments [mean change of 3.78 ms (95 % CI (2.93, 4.62), p < 0.001) and 0.23 mg/g (95 % CI (0.16, 0.29), p < 0.001), respectively]. Change in T2* values varied significantly between segments (p < 0.001) with greatest improvement in the apical inferoseptum [4.26 ms, 95 % CI (2.42, 6.11)] and least improvement in the basal anteroseptum [2.95 ms, 95 % CI (1.37, 4.54)]. The largest improvement in T2* values was noted in patients treated with deferiprone [4.96 ms, 95 % CI (2.34, 7.58)]. There was a statistically significant difference in improvement in CIC values between chelation regimens (p = 0.016). This is the first study to report heterogeneity in response to iron chelating drugs with variable segmental changes in T2* values.

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

    PubMed

    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.

  16. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    PubMed

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

  17. Introducing saccharic acid as an efficient iron chelate to enhance photo-Fenton degradation of organic contaminants.

    PubMed

    Subramanian, Gokulakrishnan; Madras, Giridhar

    2016-11-01

    The identification of iron chelates that can enhance photo-Fenton degradation is of great interest in the field of advanced oxidation process. Saccharic acid (SA) is a polyhydroxy carboxylic acid and completely non-toxic. Importantly, it can effectively bind Fe(III) as well as induce photoreduction of Fe(III). Despite having these interesting properties, the effect of SA on photo-Fenton degradation has not been studied. Herein, we demonstrate the first assessment of SA as an iron chelate in photo-Fenton process using methylene blue (MB) as a model organic contaminant. Our results demonstrate that SA has the ability to (i) enhance the photo-Fenton degradation of MB by about 11 times at pH 4.5 (ii) intensify photochemical reduction of Fe(III) to Fe(II) by about 17 times and (iii) accelerate the rate of consumption of H2O2 in photo-Fenton process by about 5 times (iv) increase the TOC reduction by about 2 times and (v) improve the photo-Fenton degradation of MB in the presence of a variety of common inorganic ions and organic matter. The influential properties of SA on photo-Fenton degradation is attributed to the efficient photochemical reduction of Fe(III) via LMCT (ligand to metal charge transfer reaction) to Fe(II), which then activated H2O2 to generate OH and accelerated photo-Fenton degradation efficiency. Moreover, the effect of operational parameters such as oxidant: contaminant (H2O2: MB) ratio, catalyst: contaminant (Fe(III)SA: MB) ratio, Fe(III): SA stoichiometry and pH on the degradation of MB by photo-Fenton in the presence of SA is demonstrated. Importantly, SA assisted photo-Fenton caused effective degradation of MB and 4-Chlorophenol under natural sunlight irradiation in natural water matrix. The findings strongly support SA as a deserving iron chelate to enhance photo-Fenton degradation.

  18. The role of chelating agents on the structural and magnetic properties of α-Fe2O3 nanoparticles

    NASA Astrophysics Data System (ADS)

    Lima, R. J. S.; Jesus, J. R.; Moura, K. O.; Jesus, C. B. R.; Duque, J. G. S.; Meneses, C. T.

    2011-06-01

    In this work we have studied the role of the addition of chelating agents on the structural and magnetic properties of α-Fe2O3 nanoparticles obtained by the co-precipitation method. The precursors were prepared for the addition of different concentrations of the chelating agents: sucrose and glycerine. To obtain the nanoparticles, these precursors were heated in the temperature range between 200 and 400 °C. The samples have been characterized via x-ray diffraction (XRD), scanning electron microscopy (SEM), and magnetization measurements. The XRD data confirm that the crystalline phase is already formed at temperatures around 200 °C and there is a preferential growth to the (110) crystallographic plane to the sample at 0.01 mol/l of sucrose. Besides, a more careful analysis performed in the XRD, SEM, and zero field cooling and field cooling magnetization data clearly show the dependence of the size, shape, and size distribution of the samples as function of the chelating agent concentration.

  19. A new kind of chelating agent with low pH value applied in the TSV CMP slurry

    NASA Astrophysics Data System (ADS)

    Jiao, Hong; Yuling, Liu; Baoguo, Zhang; Xinhuan, Niu; Liying, Han

    2015-12-01

    TSV (through silicon via) is an emerging technology, which can realize micromation compared with the conventional packaging and extend Moore's law. Chemical mechanical polishing (CMP) is one of the most important steps in the process of TSV manufacture, and it is an enabling technology to extend Moore's law in the past two decades. Low pressure, low abrasive and low pH value are the main requirements for copper interconnection. In this paper, the effect of different kinds of TSV slurry with FA/O II or FA/O IV type chelating agent on CMP are studied. All kinds of slurry used in this study are alkaline with no added inhibitors. From the experiment results, it can be seen that the copper removal rate and surface roughness achieved by using the FA/O IV type chelating agent with a low pH value is superior to using the FA/O II type chelating agent. Project supported by the Major National Science and Technology Special Projects (No. 2009ZX02308), the Fund Project of Hebei Provincial Department of Education, China (No. QN2014208), the Natural Science Foundation of Hebei Province, China (No. E2013202247), and the Colleges and Universities Scientific Research Project of Hebei Province, China (No. Z2014088).

  20. Headgroup interactions and ion flotation efficiency in mixtures of a chelating surfactant, different foaming agents, and divalent metal ions.

    PubMed

    Svanedal, Ida; Boija, Susanne; Norgren, Magnus; Edlund, Håkan

    2014-06-10

    The correlation between interaction parameters and ion flotation efficiency in mixtures of chelating surfactant metal complexes and different foaming agents was investigated. We have recently shown that chelating surfactant 2-dodecyldiethylenetriaminepentaacetic acid (4-C12-DTPA) forms strong coordination complexes with divalent metal ions, and this can be utilized in ion flotation. Interaction parameters for mixed micelles and mixed monolayer formation for Mg(2+) and Ni(2+) complexes with the chelating surfactant 4-C12-DTPA and different foaming agents were calculated by Rubingh's regular solution theory. Parameters for the calculations were extracted from surface tension measurements and NMR diffusometry. The effects of metal ion coordination on the interactions between 4-C12-DTPA and the foaming agents could be linked to a previously established difference in coordination chemistry between the examined metal ions. As can be expected from mixtures of amphoteric surfactants, the interactions were strongly pH-dependent. Strong correlation was found between interaction parameter β(σ) for mixed monolayer formation and the phase-transfer efficiency of Ni(2+) complexes with 4-C12-DTPA during flotation in a customized flotation cell. In a mixture of Cu(2+) and Zn(2+), the significant difference in conditional stability constants (log K) between the metal complexes was utilized to selectively recover the metal complex with the highest log K (Cu(2+)) by ion flotation. Flotation experiments in an excess concentration of metal ions confirmed the coordination of more than one metal ion to the headgroup of 4-C12-DTPA.

  1. Regulation of gene expression in bovine blastocysts in response to oxygen and the iron chelator desferrioxamine.

    PubMed

    Harvey, A J; Kind, K L; Thompson, J G

    2007-07-01

    Low (2%) oxygen conditions during postcompaction culture of bovine blastocysts improve embryo quality and are associated with small increases in the expression of glucose transporter 1 (SLC2A1), anaphase promoting complex (ANAPC1), and myotrophin (MTPN), suggesting a role for oxygen in the regulation of embryo development, mediated through oxygen-sensitive gene expression. However, bovine embryos, to at least the blastocyst stage, lack detectable levels of the key regulator of oxygen-sensitive gene expression, hypoxia-inducible 1 alpha (HIF1A), while the less well-characterized HIF2 alpha protein is readily detectable. Here we report that other key HIF1 regulated genes are not significantly altered in their expression pattern in bovine blastocysts in response to reduced oxygen concentrations postcompaction-with the exception of lactate dehydrogenase A (LDHA), which was significantly increased following 2% oxygen culture. Antioxidant enzymes have been suggested as potential HIF2 target genes, but their expression was not altered following low-oxygen culture in the bovine blastocyst. The addition of desferrioxamine (an iron chelator and inducer of HIF-regulated gene expression) during postcompaction stages significantly increased SLC2A1, LDHA, inducible nitric oxide synthase (NOS2A), and MTPN gene expression in bovine blastocysts, although development to the blastocyst stage was not significantly affected. These results further suggest that expression of genes, known to be regulated by oxygen via HIF-1 in somatic cells, is not influenced by oxygen during preimplantation postcompaction bovine embryo development. Oxygen-regulated expression of LDHA and SLC2A1 in bovine blastocysts suggests that regulation of these genes may be mediated by HIF2. Furthermore, the effect of a reduced-oxygen environment on gene expression can be mimicked in vitro through the use of desferrioxamine. These results further support our data that the bovine blastocyst stage embryo is unique in

  2. Bifunctional chelates of RH-105 and AU199 as potential radiotherapeutic agents

    SciTech Connect

    Droege, P.

    1997-03-01

    Research is presented on new bifunctional chelating ligand systems with stability on the macroscopic and radiochemical levels. The synthesis of the following complexes are described: rhodium 105, palladium 109, and gold 198.

  3. Lead(II) binding to the chelating agent D-penicillamine in aqueous solution.

    PubMed

    Sisombath, Natalie S; Jalilehvand, Farideh; Schell, Adam C; Wu, Qiao

    2014-12-01

    A spectroscopic investigation of the complexes formed between the Pb(II) ion and D-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet-visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S(-) → Pb(II) ligand-to-metal charge-transfer. The downfield (13)C NMR chemical shift for the penicillamine COO(-) group confirmed Pb(II) coordination. The (207)Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state (207)Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb-S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ((207)Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a Pb(II)S2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)](2-n) (n = 0-1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.

  4. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    NASA Astrophysics Data System (ADS)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  5. The Copper Sulfide Coating on Polyacrylonitrile with Chelating Agents by an Electroless Deposition Method and its EMI Shielding Effectiveness

    SciTech Connect

    Roan, M.-L.; Chen, Y.-H.; Huang, C.-Y.

    2008-08-28

    In this study, a variety of concentrations of chelating agents were added to obtain the anchoring effect and chelating effect in the electroless plating bath. The mechanism of the Cu{sub x(x=1,2)}S growth and the electromagnetic interference shielding effectiveness (EMI SE) of the composite were studied. It was found that the vinyl acetate residued in PAN substrate would be purged due to the swelling effect by chelating agents solution. And then, the anchoring effect occurred due to the hydrogen bonding between the pits of PAN substrate and the chelating agent. Consequently, the copper sulfide layer deposited by the electroless plating reaction with EDTA and TEA. The swelling degree (S{sub d}) was proposed and evaluated from the FT-IR spectra. The relationship between swelling degree of the PAN films and EDTA (C) is expressed as: S{sub d} = 0.13+0.90xe and (-15.15C). And TEA series is expressed as: S{sub d} = 0.07+1.00xe and (-15.15C). On the other hand, the FESEM micrograph showed that the average thickness of copper sulfide increased from 76 nm to 383 nm when the concentration of EDTA increased from 0.00M to 0.20M. Consequently, the EMI SE of the composites increased from 10{approx}12 dB to 25{approx}27 dB. The GIA-XRD analyze indicated that the deposited layer consisted of CuS and Cu{sub 2}S.

  6. Reversed-phase high-performance liquid chromatography of non-transferrin-bound iron and some hydroxypyridone and hydroxypyrone chelators.

    PubMed

    el-Jammal, A; Templeton, D M

    1994-08-05

    The pursuit of orally available Fe(III) chelating agents has resulted in several clinical trials of 1,2-dimethyl-3-hydroxypyrid-4-one (CP20). Chromatography of this and related Fe chelators on silica-based columns has proven difficult due to unwanted interactions with the stationary phase, including with contaminating Fe bound to silanol groups. By addition of Fe3+ (50 microM ferric ammonium citrate) to an acidified aqueous mobile phase, we have successfully separated a series of hydroxypyridones-including CP20-and the related pyrones maltol and ethylmaltol by HPLC on microBondapak C18. Complexation occurs with these agents even at low pH, and they elute in an order consistent with the partition coefficients of their Fe(III) complexes. By the reverse strategy of adding ethylmaltol to the mobile phase, chelatable Fe was chromatographed and the peak response at 500 nm was linear down to a detection limit below 0.5 microM. This method was applied to pooled serum and to serum spiked with Fe after filtration at 10 kDa cut-off. The direct determination of non-transferrin-bound Fe at micromolar concentrations in serum is possible with this approach.

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

    PubMed

    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. The effect of chelating agent on the separation of Fe(III) and Ti(IV) from binary mixture solution by cation-exchange membrane.

    PubMed

    Kir, Esengül; Cengeloğlu, Yunus; Ersöz, Mustafa

    2005-12-15

    The competitive transport of Fe(III) and Ti(IV) ions and the effect of chelating agents on separation from binary mixture solutions through charged polysulfone cation-exchange membrane (SA3S) has been studied under Donnan dialysis conditions. The amount of chelating agent was taken as an equimolar of Fe(III) ion in the feed phase. In this process, the membrane separated two electrolyte solutions: the feed solution, initially containing metal salts (Fe, Ti), or metal salts solution, containing a chelating agent, and the other side (receiver solution) being HCl solution. An external potential field is not applied. It was observed that the chelating agents affect the metal transport; the transport of Fe(III) is decreased and the transport of Ti(IV) is increased.

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

    PubMed Central

    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

  10. Effect of pH on the release of radionuclides and chelating agents from cement-solidified decontamination ion-exchange resins collected from operating nuclear power stations

    SciTech Connect

    McIsaac, C.V.; Akers, D.W.; McConnell, J.W. )

    1991-06-01

    Data are presented on the physical stability and leachability of radionuclides and chelating agents from cement-solidified decontamination ion-exchange resin wastes collected from two operating commercial light water reactors. Small-scale waste--form specimens collected during solidifications performed at the Brunswick Steam Electric Plant Unit 1 and at the James A. FitzPatrick Nuclear Power Station were leach-tested and subjected to compressive strength testing in accordance with the Nuclear Regulatory Commission's Technical Position on Waste Form'' (Revision 1). Samples of untreated resin waste collected from each solidification vessel before the solidification process were analyzed for concentrations of radionuclides, selected transition metals, and chelating agents to determine the quantities of these chemicals in the waste-form specimens. The chelating agents included oxalic, citric, and picolinic acids. In order to determine the effect of leachant chemical composition and pH on the stability and leachability of the waste forms, waste-form specimens were leached in various leachants. Results of this study indicate that differences in pH do not affect releases from cement-solidified decontamination ion-exchange resin waste forms, but that differences in leachant chemistry and the presence of chelating agents may affect the releases of radionuclides and chelating agents. Also, this study indicates that the cumulative releases of radionuclides and chelating agents are similar for waste- form specimens that decomposed and those that retained their general physical form. 36 refs., 60 figs., 28 tabs.

  11. Iron acquisition by Cryptococcus neoformans.

    PubMed

    Vartivarian, S E; Cowart, R E; Anaissie, E J; Tashiro, T; Sprigg, H A

    1995-01-01

    Iron is an essential element for the growth and metabolism of microbial cells. Most pathogenic microbes elaborate powerful iron chelating agents (siderophores) to mobilize iron from ferric ligands. The pathogenic yeast, Cryptococcus neoformans has not been found to produce siderophores and its mechanism of iron acquisition is unknown. This investigation explored an alternative pathway for iron acquisition by examining the interactions of iron with the cell surface. Iron uptake experiments were conducted utilizing radiolabelled ferrous iron and ferric iron chelates, with evidence for the presence of iron(II) receptors and the generation of ferrous iron by surface reduction. Hyperbolic kinetics were found when 59FeII was presented to the organism and uptake was blocked with bathophenanthroline sulphonate, an Fe2+ chelator. The yeast also acquired iron as [59Fe3+]-citrate and [59Fe3+]-pyrophosphate while bathophenanthroline sulphonate reduced the acquisition of these ferric ligands by 48% and 52% respectively. Pre-incubation with either ferric ligand also reduced iron acquisition by 50%. KCN inhibited uptake of iron(II) by 90% and uptake of [59Fe3+]-pyrophosphate and [59Fe3+]-citrate by 46% and 56% respectively; dinitrophenol had no effect on these processes. The data suggest that C. neoformans can (i) generate ferrous iron at the cell surface via a reduction of ferric chelates, with the subsequent acquisition of the ferrous iron, and (ii) acquire iron through the interaction of ferric chelates with a surface component.

  12. Inhibition of Xanthomonas fragariae, Causative Agent of Angular Leaf Spot of Strawberry, through Iron Deprivation

    PubMed Central

    Henry, Peter M.; Gebben, Samantha J.; Tech, Jan J.; Yip, Jennifer L.; Leveau, Johan H. J.

    2016-01-01

    In commercial production settings, few options exist to prevent or treat angular leaf spot (ALS) of strawberry, a disease of economic importance and caused by the bacterial pathogen Xanthomonas fragariae. In the process of isolating and identifying X. fragariae bacteria from symptomatic plants, we observed growth inhibition of X. fragariae by bacterial isolates from the same leaf macerates. Identified as species of Pseudomonas and Rhizobium, these isolates were confirmed to suppress growth of X. fragariae in agar overlay plates and in microtiter plate cultures, as did our reference strain Pseudomonas putida KT2440. Screening of a transposon mutant library of KT2440 revealed that disruption of the biosynthetic pathway for the siderophore pyoverdine resulted in complete loss of X. fragariae antagonism, suggesting iron competition as a mode of action. Antagonism could be replicated on plate and in culture by addition of purified pyoverdine or by addition of the chelating agents tannic acid and dipyridyl, while supplementing the medium with iron negated the inhibitory effects of pyoverdine, tannic acid and dipyridyl. When co-inoculated with tannic acid onto strawberry plants, X. fragariae’s ability to cause foliar symptoms was greatly reduced, suggesting a possible opportunity for iron-based management of ALS. We discuss our findings in the context of ‘nutritional immunity,’ the idea that plant hosts restrict pathogen access to iron, either directly, or indirectly through their associated microbiota. PMID:27790193

  13. Lead(II) binding to the chelating agent d-penicillamine in aqueous solution

    DOE PAGES

    Sisombath, Natalie S.; Jalilehvand, Farideh; Schell, Adam C.; ...

    2014-11-11

    Here, a spectroscopic investigation of the complexes formed between the Pb(II) ion and d-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet–visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S– → Pb(II) ligand-to-metal charge-transfer. The downfield 13C NMR chemical shift for the penicillamine COO– group confirmed Pb(II) coordination. The 207Pb NMR chemical shifts were confined to a narrow range betweenmore » 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state 207Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb–S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ(207Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a PbIIS2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)]2–n (n = 0–1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.« less

  14. Lead(II) binding to the chelating agent d-penicillamine in aqueous solution

    SciTech Connect

    Sisombath, Natalie S.; Jalilehvand, Farideh; Schell, Adam C.; Wu, Qiao

    2014-11-11

    Here, a spectroscopic investigation of the complexes formed between the Pb(II) ion and d-penicillamine (H2Pen), a chelating agent used in the treatment of lead poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II) ≈ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0). Ultraviolet–visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently showed an absorption peak at 298 nm for S → Pb(II) ligand-to-metal charge-transfer. The downfield 13C NMR chemical shift for the penicillamine COO group confirmed Pb(II) coordination. The 207Pb NMR chemical shifts were confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)-penicillamine solutions, indicating only small variations in the speciation, even in large penicillamine excess. Those chemical shifts are considerably deshielded, relative to the solid-state 207Pb NMR isotropic chemical shift of 909 ppm obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination. The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra obtained for these solutions were well-modeled with two Pb–S and two Pb-(N/O) bonds with mean distances 2.64 ± 0.04 Å and 2.45 ± 0.04 Å, respectively. The combined spectroscopic results, reporting δ(207Pb) ≈ 1870 ppm and λmax ≈ 298 nm for a PbIIS2NO site, are consistent with a dominating 1:2 lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)]2–n (n = 0–1) coordination in alkaline solutions, and provide useful structural information on how penicillamine can function as an antidote against lead toxicity in vivo.

  15. Effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on ferritin concentration in Mexican schoolchildren: a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Iron deficiency is one of the most common nutritional deficiencies worldwide. It is more prevalent when iron requirements are increased during pregnancy and during growth spurts of infancy and adolescence. The last stage in the process of iron depletion is characterized by a decrease in hemoglobin concentration, resulting in iron deficiency anemia. Iron deficiency, even before it is clinically identified as anemia, compromises the immune response, physical capacity for work, and intellectual functions such as attention level. Therefore, interventions addressing iron deficiency should be based on prevention rather than on treatment of anemia. The aim of this study was to compare short- and medium-term effects on ferritin concentration of daily supplementation with ferrous sulfate or iron bis-glycinate chelate in schoolchildren with iron deficiency but without anemia. Methods Two hundred schoolchildren from public boarding schools in Mexico City who had low iron stores as assessed by serum ferritin concentration but without anemia were randomly assigned to a daily supplement of 30 mg/day of elemental iron as ferrous sulfate or iron bis-glycinate chelate for 12 weeks. Iron status was evaluated at baseline, one week post-supplementation (short term), and 6 months (medium term) after supplementation. Results Ferritin concentration increased significantly between baseline and post-supplementation as well as between baseline and 6 months after supplementation. One week post-supplementation no difference was found in ferritin concentration between iron compounds, but 6 months after supplementation ferritin concentration was higher in the group that received bis-glycinate chelate iron. However, there is no difference in the odds for low iron storage between 6 months after supplementation versus the odds after supplementation; nor were these odds different by type of supplement. Hemoglobin concentration did not change significantly in either group after

  16. Oxidation and reduction of bis(imino)pyridine iron dinitrogen complexes: evidence for formation of a chelate trianion.

    PubMed

    Tondreau, Aaron M; Stieber, S Chantal E; Milsmann, Carsten; Lobkovsky, Emil; Weyhermüller, Thomas; Semproni, Scott P; Chirik, Paul J

    2013-01-18

    Oxidation and reduction of the bis(imino)pyridine iron dinitrogen compound, ((iPr)PDI)FeN(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N═CMe)(2)C(5)H(3)N) has been examined to determine whether the redox events are metal or ligand based. Treatment of ((iPr)PDI)FeN(2) with [Cp(2)Fe][BAr(F)(4)] (BAr(F)(4) = B(3,5-(CF(3))(2)-C(6)H(3))(4)) in diethyl ether solution resulted in N(2) loss and isolation of [((iPr)PDI)Fe(OEt(2))][BAr(F)(4)]. The electronic structure of the compound was studied by SQUID magnetometry, X-ray diffraction, EPR and zero-field (57)Fe Mössbauer spectroscopy. These data, supported by computational studies, established that the overall quartet ground state arises from a high spin iron(II) center (S(Fe) = 2) antiferromagnetically coupled to a bis(imino)pyridine radical anion (S(PDI) = 1/2). Thus, the oxidation event is principally ligand based. The one electron reduction product, [Na(15-crown-5)][((iPr)PDI)FeN(2)], was isolated following addition of sodium naphthalenide to ((iPr)PDI)FeN(2) in THF followed by treatment with the crown ether. Magnetic, spectroscopic, and computational studies established a doublet ground state with a principally iron-centered SOMO arising from an intermediate spin iron center and a rare example of trianionic bis(imino)pyridine chelate. Reduction of the iron dinitrogen complex where the imine methyl groups have been replaced by phenyl substituents, ((iPr)BPDI)Fe(N(2))(2) resulted in isolation of both the mono- and dianionic iron dinitrogen compounds, [((iPr)BPDI)FeN(2)](-) and [((iPr)BPDI)FeN(2)](2-), highlighting the ability of this class of chelate to serve as an effective electron reservoir to support neutral ligand complexes over four redox states.

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

    PubMed

    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.

  18. Protection against hydrogen peroxide-mediated cytotoxicity in Friedreich's ataxia fibroblasts using novel iron chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone class.

    PubMed

    Lim, C K; Kalinowski, D S; Richardson, D R

    2008-07-01

    Iron-loading diseases remain an important problem because of the toxicity of iron-catalyzed redox reactions. Iron loading occurs in the mitochondria of Friedreich's ataxia (FA) patients and may play a role in its pathogenesis. This suggests that iron chelation therapy could be useful. We developed previously the lipophilic iron chelators known as the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) ligands and identified 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH) as the most promising analog. Hence, this study assessed the efficacy of PCTH and other PCIH analogs compared with various chelators, including deferiprone and desferrioxamine (DFO). Age- and sex-matched control and FA fibroblasts were preincubated with iron chelators and subsequently challenged with 50 microM H2O2 for up to 24 h. The current study demonstrates an interesting structure-activity relationship among the closely related PCIH series of ligands, with only PCTH being highly effective at preventing H2O2-induced cytotoxicity. PCTH increased FA fibroblast cell viability by up to 70%, whereas DFO rescued viability by 1 to 5% only. Hence, PCTH, which was well tolerated by cells was far more effective than DFO at preventing oxidative stress. It is noteworthy that kinetic studies demonstrated PCTH to rapidly penetrate cells to induce 59Fe efflux, whereas DFO, PCIH, 2-pyridylcarboxaldehyde benzoyl hydrazone, and 2-pyridylcarboxaldehyde m-bromobenzoyl hydrazone were far slower, indicating it is the rate of chelator permeation that is crucial for protection against H2O2. In addition, PCTH was found to be as effective as or more effective than conventional radical scavengers or the antioxidant idebenone (which has undergone clinical trials) at protecting cells against H2O2-mediated cytotoxicity. These findings further indicate the potential of PCTH for treatment of iron overload.

  19. Comparison of the antibacterial activity of chelating agents using the agar diffusion method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The agar diffusion assay was used to examine antibacterial activity of 2 metal chelators. Concentrations of 0 to 40 mM of ethylenediaminetetraacetic acid (EDTA) and ethylenediamine-N,N’-disuccinic acid (EDDS) were prepared in 1.0 M potassium hydroxide (KOH). The pH of the solutions was adjusted to 1...

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

    PubMed

    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.

  1. Transfusional Iron Overload in a Cohort of Children with Sickle Cell Disease: Impact of Magnetic Resonance Imaging, Transfusion Method, and Chelation

    PubMed Central

    Stanley, Helen M.; Friedman, David F.; Webb, Jennifer

    2016-01-01

    Background Transfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied. Procedure Iron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed. Results Among 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2‐MRI in 2006. Among subjects with at least two R2‐MRI examinations, median LIC improved (13.2–7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P < 0.001) after a median of 2.7 years and ferritin improved (2,471–392 ng/ml, P < 0.001) after a median of 4.2 years. Final serum ferritin and LIC correlated negatively with the proportion of transfusions administered by erythrocytapheresis and chelation adherence. Conclusions Routine liver R2‐MRI should be performed in individuals with SCD who receive chronic red cell transfusions. Adherence with chelation should be assessed regularly and erythrocytapheresis utilized when feasible to minimize iron loading or reduce iron stores accumulated during periods of simple transfusion. PMID:27100139

  2. Reversible precipitation of bovine serum albumin by metal ions and synthesis, structure and reactivity of new tetrathiometallate chelating agents.

    PubMed

    Lee, Victoria E; Schulman, Joshua M; Stiefel, Edward I; Lee, Catherine Coyle

    2007-11-01

    Independent research is an important component of any undergraduate chemistry program. This article reports the findings of two of many undergraduate research projects directed by Ed Stiefel in the hopes that the results will be inspiring and useful to the scientific community. The neurological disorders associated with insufficient copper in Menkes disease and an excess of copper in Wilson's disease are well established; however, recent evidence suggests that copper may also be involved in other disorders, such as Alzheimer's, angiogenesis, and prion diseases. The exact role of copper, however, is uncertain. This study examines the role of copper and zinc in the formation of protein deposits and the chelation and removal of the metal ions to reverse the process. The bovine serum albumin (BSA) protein forms a precipitate after the addition of approximately 6 copper(II) atoms or 8 zinc(II) atoms. Other metal ions, such as Ca(II), Al(III), Ni(II), and Co(II), did not precipitate the BSA even when the metal ion to BSA ratios were in excess of 1000. The copper and zinc protein precipitates returned to solution after addition of the chelating agents, ethylenediaminetetraacetic acid (EDTA) or tetrathiometallates [(MS(4)(2-)), where M=Mo, W]. Two new choline and acetylcholine tetrathiomolybdate and tetrathiotungstate chelating agents have been synthesized and characterized. The infrared (IR) and X-ray crystal structures of the complexes revealed that the (MS(4)(2-)) cores had approximate T(d) symmetry in the choline (Ch) salts and C(2v) symmetry in the acetylcholine (AcCh) salts. The AcCh salts hydrolyzed more slowly than the ammonium or Ch salts and the tetrathiotungstate salts hydrolyzed approximately two orders of magnitude more slowly than the tetrathiomolybdate salts. The slower hydrolysis of tetrathiotungstate may make it more useful as an inorganic reagent and therapeutic agent.

  3. Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

    SciTech Connect

    Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile; Dorandeu, Frédéric; Boudry, Isabelle

    2013-10-15

    Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.

  4. Novel immunosuppressive agent caerulomycin A exerts its effect by depleting cellular iron content

    PubMed Central

    Kaur, Suneet; Srivastava, Gautam; Sharma, Amar Nath; Jolly, Ravinder S

    2015-01-01

    Background and Purpose Recently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action. Experimental Approach Jurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry. Key Results CaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21CIP1/WAF1. The effect of CaeA on cell proliferation was reversible. Conclusions and Implications CaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron. PMID:25537422

  5. Effect of metal chelators on the aggregation of beta-amyloid peptides in the presence of copper and iron.

    PubMed

    Tahmasebinia, Foozhan; Emadi, Saeed

    2017-04-01

    Amyloid β (Aβ) fibrils and amorphous aggregates are found in the brain of patients with Alzheimer's disease (AD), and are implicated in the etiology of AD. The metal imbalance is also among leading causes of AD, owing to the fact that Aβ aggregation takes place in the synaptic cleft where Aβ, Cu(II) and Fe(III) are found in abnormally high concentrations. Aβ40 and Aβ42 are the main components of plaques found in afflicted brains. Coordination of Cu(II) and Fe(III) ions to Aβ peptides have been linked to Aβ aggregation and production of reactive oxygen species, two key events in the development of AD pathology. Metal chelation was proposed as a therapy for AD on the basis that it might prevent Aβ aggregation. In this work, we first examined the formation of Aβ40 and Aβ42 aggregates in the presence of metal ions, i.e. Fe(III) and Cu(II), which were detected by fluorescence spectroscopy and atomic force microscopy. Second, we studied the ability of the two chelators, ethylenediaminetetraacetic acid and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol), to investigate their effect on the availability of these metal ions to interact with Aβ and thereby their effect on Aβ accumulation. Our findings show that Fe(III), but not Cu(II), promote aggregation of both Aβ40 and Aβ42. We also found that only clioquinol decreased significantly iron ion-induced aggregation of Aβ42. The presence of ions and/or chelators also affected the morphology of Aβ aggregates.

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

    PubMed Central

    Kell, Douglas B

    2009-01-01

    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 (su)peroxide 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-oxidants. The reduction of redox

  7. α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators That Are Promising for Revival of Gallium in Cancer Chemotherapy.

    PubMed

    Cao, Shuhong; Chen, Xiahui; Chen, Ligen; Chen, Jingwen

    2016-03-10

    The metal-based drugs have gained increasing attention in the fight against cancer. Ga(III) in the form of inorganic salts has demonstrated efficacy in the treatment of a number of malignancies in experimental animals and humans, and has therefore attracted considerable pharmaceutical interest. However, the poor hydrolytic stability of Ga(III) in physiological medium owing to its property of hard Lewis acid prevents its widespread use in systemic cancer chemotherapy. Complexation of suitable chelators capable of stabilising Ga(III) against hydrolysis affords an opportunity for overcoming this drawback. Thiosemicarbazone (TSC) derivatives, a class of well-studied iron chelators featuring softer donor sulfur, also were evaluated to possess antineoplastic activities in an arrary of tumour cell lines. The structural modifications can affect the activities of TSCs, and related structure-activity relationships (SAR) have been studied over these years. Combination of Ga(III) and TSCs that are both pharmaceutically active has proved to exert synergistic effects of each component in one compound in most cases, and may produce more potent Ga(III) drugs. In this review, the SAR of α(N)-heterocyclic thiosemicarbazone (HCT) analogues, a family of TSCs, were scrupulously surveyed, and the effect of Ga(III) complexation on their anticancer activity sparsely reported in literature was comparatively examined, in order to stimulate further advances in the field of gallium-based anticancer drugs.

  8. Acetylacetone as chelating reagent, extracting solvent, and electrolysis medium: Polarographic determination of uranium(VI) and iron(III).

    PubMed

    Fujinaga, T; Lee, H L

    1977-06-01

    The chelating reagent acetylacetone has been examined as a polarographic medium; a method for its purification has been developed and it is found that the specific conductance is 4.2 x 10(-8) mho/cm, the accessible potential ranges are from -0.16 to -2.26 V vs. Ag/0.1M AgClO(4) for the pure solvent and from -0.35 to -2.20 V in the solvent after extraction. In pure solvent ferric acetylacetonate exhibits one wave and the uranyl complex gives two waves. After extraction from aqueous solution at pH 6.8-7.0, both metal acetylacetonates are reduced more reversibly and at more positive potential than in the pure solvent. Calibration curves are linear in the range 10(-5) -10(-3)M metal ion in the extract. The direct polarographic determination of uranium and iron in acetylacetone after extraction of the chelate from aqueous solution has been developed.

  9. Nitric oxide suppresses tumor cell migration through N-Myc downstream-regulated gene-1 (NDRG1) expression: role of chelatable iron.

    PubMed

    Hickok, Jason R; Sahni, Sumit; Mikhed, Yuliya; Bonini, Marcelo G; Thomas, Douglas D

    2011-12-02

    N-Myc downstream-regulated gene 1 (NDRG1) is a ubiquitous cellular protein that is up-regulated under a multitude of stress and growth-regulatory conditions. Although the exact cellular functions of this protein have not been elucidated, mutations in this gene or aberrant expression of this protein have been linked to both tumor suppressive and oncogenic phenotypes. Previous reports have demonstrated that NDRG1 is strongly up-regulated by chemical iron chelators and hypoxia, yet its regulation by the free radical nitric oxide ((•)NO) has never been demonstrated. Herein, we examine the chemical biology that confers NDRG1 responsiveness at the mRNA and protein levels to (•)NO. We demonstrate that the interaction of (•)NO with the chelatable iron pool (CIP) and the appearance of dinitrosyliron complexes (DNIC) are key determinants. Using HCC 1806 triple negative breast cancer cells, we find that NDRG1 is up-regulated by physiological (•)NO concentrations in a dose- and time-dependant manner. Tumor cell migration was suppressed by NDRG1 expression and we excluded the involvement of HIF-1α, sGC, N-Myc, and c-Myc as upstream regulatory targets of (•)NO. Augmenting the chelatable iron pool abolished (•)NO-mediated NDRG1 expression and the associated phenotypic effects. These data, in summary, reveal a link between (•)NO, chelatable iron, and regulation of NDRG1 expression and signaling in tumor cells.

  10. Effect of Chelating Agents on the Stability of Nano-TiO2 Sol Particles for Sol-Gel Coating.

    PubMed

    Maeng, Wan Young; Yoo, Mi

    2015-11-01

    Agglomeration of sol particles in a titanium alkoxide (tetrabutyl orthotitanate (TBOT), > 97%) solution during the hydrolysis and condensation steps makes the sol solution difficult to use for synthesizing homogeneous sol-gel coating. Here, we have investigated the effect of stabilizing agents (acetic acid and ethyl acetoacetate (EAcAc)) on the agglomeration of Ti alkoxide particles during hydrolysis and condensation in order to determine the optimized conditions for controlling the precipitation of TiO2 particles. The study was conducted at R(AC) ([acetic acid]/[TBOT]) = 0.1-5 and R(EAcAc)([EAcAc]/[TBOT]) = 0.05-0.65. We also studied the effects of a basic catalyst ethanolamine (ETA), water, and HCl on sol stability. The chelating ligands in the precursor sol were analyzed with FT-IR. The coating properties were examined by focused ion beam. The stabilizing agents (acetic acid and EAcAc) significantly influenced the agglomeration and precipitation of TBOT precursor particles during hydrolysis. As R(AC) and R(EAcAc) increased, the agglomeration remarkably decreased. The stability of the sol with acetic acid and EAcAc arises from the coordination of the chelating ligand to TBOT that hinders hydrolysis and condensation. A uniform fine coating (thickness: 30 nm) on stainless steel was obtained by using an optimized sol with R(AC) = 0.5 and R(EAcAc) = 0.65.

  11. Synergetic effect of chelating agent and nonionic surfactant for benzotriazole removal on post Cu-CMP cleaning

    NASA Astrophysics Data System (ADS)

    Yanlei, Li; Yuling, Liu; Chenwei, Wang; Yue, Li

    2016-08-01

    The cleaning of copper interconnects after chemical mechanical planarization (CMP) process is a critical step in integrated circuits (ICs) fabrication. Benzotriazole (BTA), which is used as corrosion inhibitor in the copper CMP slurry, is the primary source for the formation of organic contaminants. The presence of BTA can degrade the electrical properties and reliability of ICs which needs to be removed by using an effective cleaning solution. In this paper, an alkaline cleaning solution was proposed. The alkaline cleaning solution studied in this work consists of a chelating agent and a nonionic surfactant. The removal of BTA was characterized by contact angle measurements and potentiodynamic polarization studies. The cleaning properties of the proposed cleaning solution on a 300 mm copper patterned wafer were also quantified, total defect counts after cleaning was studied, scanning electron microscopy (SEM) review was used to identify types of BTA to confirm the ability of cleaning solution for BTA removal. All the results reveal that the chelating agent can effectively remove the BTA residual, nonionic surfactant can further improve the performance. Project supported by the Natural Science Foundation of Hebei Province, China (No. F2015202267) and the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology (No. 2015007).

  12. Tuning the dissolution kinetics of wollastonite via chelating agents for CO2 sequestration with integrated synthesis of precipitated calcium carbonates.

    PubMed

    Zhao, Huangjing; Park, Youngjune; Lee, Dong Hyun; Park, Ah-Hyung Alissa

    2013-09-28

    Carbon mineralization has recently received much attention as one of the most promising options for CO2 sequestration. The engineered weathering of silicate minerals as a means of permanent carbon storage has unique advantages such as the abundance of naturally occurring calcium and magnesium-bearing minerals and the formation of environmentally-benign and geologically stable solids via a thermodynamically favored carbonation reaction. However, several challenges need to be overcome to successfully deploy carbon mineralization on a large scale. In particular, the acceleration of the rate-limiting mineral dissolution step along with process optimization is essential to ensure the economic feasibility of the proposed carbon storage technology. In this study, the effect of various types of chelating agents on the dissolution rate of calcium-bearing silicate mineral, wollastonite, was explored to accelerate its weathering rate. It was found that chelating agents such as acetic acid and gluconic acid significantly improved the dissolution kinetics of wollastonite even at a much diluted concentration of 0.006 M by complexing with calcium in the mineral matrix. Calcium extracted from wollastonite was then reacted with a carbonate solution to form precipitated calcium carbonate (PCC), while tuning the particle size and the morphological structure of PCC to mimic commercially available PCC-based filler materials.

  13. Technical note: assessing the functional capacity of mitochondria isolated from lactating mammary tissue: choose your chelating agent wisely.

    PubMed

    Hadsell, D L; George, J; Abraham, P A; Collier, R J; Lambert, B D

    2009-05-01

    Previous work has indicated that respiratory activity of mitochondrial preparations prepared from lactating mammary tissue is often much lower than that of mitochondria isolated from other organs such as the liver. Initial studies in our own laboratory also found that mammary mitochondria prepared from lactating mice had much lower ATP synthesis activity than those isolated from liver tissue obtained from the same animals. In this paper, we describe an improved procedure for obtaining coupled mitochondria from the mammary tissue of lactating mice. Using a high-throughput assay for mitochondrial ATP synthesis, we demonstrated that mammary mitochondria, unlike liver mitochondria, are sensitive to the concentration of bovine serum albumin and to the choice of chelating agent used in the preparation and assay buffers. Mammary mitochondria prepared and assayed in buffers containing 1 mM ethylene glycol-bis-(beta-aminoethyl ether)-N,N' tetraacetic acid (EGTA) and 0.4% bovine serum albumin have a similar ATP synthesis activity as liver mitochondria. In addition, we show that the chelating agent EDTA ablates the ATP synthesis capacity of mammary mitochondria through a mechanism that does not involve the release of cytochrome c. We also demonstrate that these improved isolation and assay procedures are both scalable and applicable to bovine mammary tissue, and we describe optimal conditions for cryopreservation and recovery of functionally active mitochondria. This work will facilitate future studies aimed at determining the importance of mammary mitochondria to milk production.

  14. Synthesis, physical-chemical characterisation and biological evaluation of novel 2-amido-3-hydroxypyridin-4(1H)-ones: Iron chelators with the potential for treating Alzheimer's disease.

    PubMed

    Gaeta, Alessandra; Molina-Holgado, Francisco; Kong, Xiao L; Salvage, Sarah; Fakih, Sarah; Francis, Paul T; Williams, Robert J; Hider, Robert C

    2011-02-01

    A novel class of 2-amido-3-hydroxypyridin-4-one iron chelators is described. These compounds have been designed to behave as suitable molecular probes which will improve our knowledge of the role of iron in neurodegenerative conditions. Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson disease (PD), can be considered as diverse pathological conditions sharing critical metabolic processes such as protein aggregation and oxidative stress. Interestingly, both these metabolic alterations seem to be associated with the involvement of metal ions, including iron. Iron chelation is therefore a potential therapeutic approach. The physico-chemical (pK(a), pFe(3+) and logP) and biological properties (inhibition of iron-containing enzymes) of these chelators have been investigated in order to obtain a suitable profile for the treatment of neurodegenerative conditions. Studies with neuronal cell cultures confirm that the new iron chelators are neuroprotective against β-amyloid-induced toxicity.

  15. In vitro and in vivo biological activities of iron chelators and gallium nitrate against Acinetobacter baumannii.

    PubMed

    de Léséleuc, Louis; Harris, Greg; KuoLee, Rhonda; Chen, Wangxue

    2012-10-01

    We investigated the ability of compounds interfering with iron metabolism to inhibit the growth of Acinetobacter baumannii. Iron restriction with transferrin or 2,2-bipyridyl significantly inhibited A. baumannii growth in vitro. Gallium nitrate alone was moderately effective at reducing A. baumannii growth but became bacteriostatic in the presence of serum or transferrin. More importantly, gallium nitrate treatment reduced lung bacterial burdens in mice. The use of gallium-based therapies shows promise for the control of multidrug-resistant A. baumannii.

  16. Analytical Interference in Serum Iron Determination Reveals Iron Versus Gadolinium Transmetallation With Linear Gadolinium-Based Contrast Agents

    PubMed Central

    Fretellier, Nathalie; Poteau, Nathalie; Factor, Cécile; Mayer, Jean-François; Medina, Christelle; Port, Marc; Idée, Jean-Marc; Corot, Claire

    2014-01-01

    Objectives The purposes of this study were to evaluate the risk for analytical interference with gadolinium-based contrast agents (GBCAs) for the colorimetric measurement of serum iron (Fe3+) and to investigate the mechanisms involved. Materials and Methods Rat serum was spiked with several concentrations of all molecular categories of GBCAs, ligands, or “free” soluble gadolinium (Gd3+). Serum iron concentration was determined by 2 different colorimetric methods at pH 4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 analyzer). Secondly, the cause of interference was investigated by (a) adding free soluble Gd3+ or Mn2+ to serum in the presence of gadobenic acid or gadodiamide and (b) electrospray ionization mass spectrometry. Results Spurious decrease in serum Fe3+ concentration was observed with all linear GBCAs (only with the Vitros DT60 technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free soluble Gd3+. Spurious hyposideremia was also observed with the free ligands present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and gadodiamide (ie, diethylene triamine pentaacetic acid and calcium-diethylene triamine pentaacetic acid bismethylamide, respectively), suggesting the formation of Fe-ligand chelate. Gadobenic acid-induced interference was blocked in a concentration-dependent fashion by adding a free soluble Gd3+ salt. Conversely, Mn2+, which has a lower affinity than Gd3+ and Fe3+ for the ligand of gadobenic acid (ie, benzyloxypropionic diethylenetriamine tetraacetic acid), was less effective (interference was only partially blocked), suggesting an Fe3+ versus Gd3+ transmetallation phenomenon at pH 4.0. Similar results were observed with gadodiamide. Mass spectrometry detected the formation of Fe-ligand with all linear GBCAs tested in the presence of Fe3+ and the disappearance of Fe-ligand after the addition of free soluble Gd3+. No Fe-ligand chelate was found in the case of the macrocyclic GBCA gadoteric

  17. Anionic cyclophanes as potential reversal agents of muscle relaxants by chemical chelation.

    PubMed

    Cameron, Kenneth S; Fielding, Lee; Mason, Rona; Muir, Alan W; Rees, David C; Thorn, Simon; Zhang, Ming Qiang

    2002-03-11

    A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1-3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium, and gallamine, in D(2)O, with association constants up to 10(4) M(-1). When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with having the most effective reversal against pancuronium (EC(50) 40 microM.

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

    PubMed

    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.

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

    PubMed

    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.

  20. Medical complications, resource utilization and costs in patients with myelofibrosis by frequency of blood transfusion and iron chelation therapy.

    PubMed

    Vekeman, Francis; Cheng, Wendy Y; Sasane, Medha; Huynh, Lynn; Duh, Mei Sheng; Paley, Carole; Mesa, Ruben A

    2015-01-01

    Iron chelation therapies (ICTs) can help eliminate iron surplus in erythrocyte transfusion-dependent (TD) patients with myelofibrosis (MF). The study assessed adjusted incidence rate ratios (aIRRs) of MF-related complications and resource utilization (RU) and adjusted mean monthly inpatient cost differences in patients with TD MF treated with versus without ICT (ICT+ vs. ICT-) using data from two healthcare claims databases. Patients with ≥ 2 MF International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes ≥ 30 days apart were included. Among 571 patients with TD MF, 103 (18%) were ICT+ and 468 (82%) were ICT-. ICT+ patients had lower rates of thrombocytopenia (aIRR: 0.55; p < 0.001), pancytopenia (0.53; p < 0.001), emergency room visits (0.84 [95% confidence interval: 0.74-0.96]) and inpatient stays (0.75 [0.64-0.87]), but higher rates of outpatient visits (1.21 [1.18-1.23]). Adjusted mean complication-related inpatient cost difference per month was lower in ICT+ patients (-$1804 [$570]; p = 0.004). ICT+ patients had significantly lower rates of acute care, but higher rates of outpatient care.

  1. Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG).

    PubMed

    Mandel, Silvia A; Amit, Tamar; Kalfon, Limor; Reznichenko, Lydia; Weinreb, Orly; Youdim, Moussa B H

    2008-10-01

    Although much progress has been made in understanding the pathogenesis of Alzheimer's disease (AD), the current therapeutic approaches are merely symptomatic, intended for the treatment of cognitive symptoms, such as disturbances in memory and perception. Novel promising strategies suggest the use of anti-inflammatory drugs, antioxidants including natural occurring plant flavonoids, iron-complexing molecules, neurotrophic factor delivery, inhibitors of the amyloid-beta protein precursor processing secretases, gamma and beta, that generate amyloid-beta peptides and the interference with lipid and cholesterol metabolism. Human epidemiological and new animal data suggest that tea drinking may decrease the incidence of dementia, AD and Parkinson's disease. In particular, its main catechin polyphenol constituent (-)-epigallocatechin-3-gallate (EGCG) has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders. This review provides a detailed overview on the multimodal activities of green tea polyphenols with emphasis on their iron chelating, neurorescue/neuroregenerative and mitochondrial stabilization action.

  2. Intrinsic dependence of the magnetic properties of CoFe2O4 nanoparticles prepared via chemical methods with addition of chelating agents

    NASA Astrophysics Data System (ADS)

    Mendonça, E. C.; Tenório, Mayara A.; Mecena, S. G.; Zucolotto, B.; Silva, L. S.; Jesus, C. B. R.; Meneses, C. T.; Duque, J. G. S.

    2015-12-01

    In this work, the effect of addition of different chelating agents on the magnetic properties of cobalt ferrite nanoparticles produced by the combining of both co-precipitation and hydrothermal methods is reported. The Rietveld analyses of X-ray diffraction patterns reveal that our samples are single phase (space group: Fd-3m) with small average sizes. The weight losses observed in the thermogravimetric measurements together with the M×H curves show that the organic contamination coming from chelating agent decomposition can give rise to misinterpretation of the magnetization measurements. Besides, analyses of the zero-field-cooled (ZFC) and field-cooled (FC) magnetization measurements and the M×H curves measured at room temperature allows us to state that both the average blocking temperature and particles size distribution are sensitive to the kind of chelating agent.

  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

    NASA Astrophysics Data System (ADS)

    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. Inhibition of Fe(2+)- and Fe(3+)- induced hydroxyl radical production by the iron-chelating drug deferiprone.

    PubMed

    Timoshnikov, V A; Kobzeva, T V; Polyakov, N E; Kontoghiorghes, G J

    2015-01-01

    Deferiprone (L1) is an effective iron-chelating drug that is widely used for the treatment of iron-overload diseases. It is known that in aqueous solutions Fe(2+) and Fe(3+) ions can produce hydroxyl radicals via Fenton and photo-Fenton reactions. Although previous studies with Fe(2+) have reported ferroxidase activity by L1 followed by the formation of Fe(3+) chelate complexes and potential inhibition of Fenton reaction, no detailed data are available on the molecular antioxidant mechanisms involved. Similarly, in vitro studies have also shown that L1-Fe(3+) complexes exhibit intense absorption bands up to 800nm and might be potential sources of phototoxicity. In this study we have applied an EPR spin trapping technique to answer two questions: (1) does L1 inhibit the Fenton reaction catalyzed by Fe(2+) and Fe(3+) ions and (2) does UV-Vis irradiation of the L1-Fe(3+) complex result in the formation of reactive oxygen species. PBN and TMIO spin traps were used for detection of oxygen free radicals, and TEMP was used to trap singlet oxygen if it was formed via energy transfer from L1 in the triplet excited state. It was demonstrated that irradiation of Fe(3+) aqua complexes by UV and visible light in the presence of spin traps results in the appearance of an EPR signal of the OH spin adduct (TMIO-OH, a(N)=14.15G, a(H)=16.25G; PBN-OH, a(N)=16.0G, a(H)=2.7G). The presence of L1 completely inhibited the OH radical production. The mechanism of OH spin adduct formation was confirmed by the detection of methyl radicals in the presence of dimethyl sulfoxide. No formation of singlet oxygen was detected under irradiation of L1 or its iron complexes. Furthermore, the interaction of L1 with Fe(2+) ions completely inhibited hydroxyl radical production in the presence of hydrogen peroxide. These findings confirm an antioxidant targeting potential of L1 in diseases related to oxidative damage.

  5. Iron chelators hydroxyurea and bathophenanthroline disulfonate inhibit DNA synthesis by different pathways.

    PubMed

    Alcaín, F J; Löw, H; Crane, F L; Navas, P

    1994-09-01

    We previously showed that thrombin-stimulated DNA synthesis in CCL 39 cells was inhibited by hydroxyurea (HU) and bathophenanthroline disulfonate (BPS) (Proc. Natl. Acad. Sci. USA, in press). A clear difference exists between these two inhibitors. Inhibition mediated by HU was immediate and must be present in the culture medium. BPS was equally effective when it was present in the medium or after preincubation, but it required at least 12 h to achieve maximal effect. The permeable form 1,10 phenanthroline had the same inhibitory effect in short-term incubations that BPS. Moreover, 1,10 phenanthroline was cytotoxic in long-term incubations indicating that the site of BPS inhibition was outside the cell. Further, long-term incubations with HU did not affect the ability of the cell to reinitiate DNA synthesis after removal of the chelator.

  6. Chelation in Metal Intoxication

    PubMed Central

    Flora, Swaran J.S.; Pachauri, Vidhu

    2010-01-01

    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. PMID:20717537

  7. Biliary excretion of cadmium in rat. III. Effects of chelating agents and change in intracellular thiol content on billiary transport and tissue distribution of cadmium

    SciTech Connect

    Cherian, M.G.

    1980-03-01

    The effects of changes in sulfur-containing intracellular ligands on biliary excretion of cadmium were studied in rats. Injection of zinc or copper salts 24 h before intravenous injection of /sup 109/CdCl/sub 2/ (1 mg/kg Cd) decreased biliary excretion of Cd. Pretreatment with cysteine (25 mg/kg) had a similar effect. Depletion of intracellular thiol by injection of diethylmaleate had little effect. The effect of chelating agents on the pharmacokinetics of Cd depended on time of administration of the agents after exposure to Cd. When chelating agents were administered 1/2 h after Cd injection (before the synthesis of metallothionein), the thiol-containing agents (2,3-dimercapto-1-propanol (BAL), DL-penicillamine, N-acetylpenicillamine, and dithioerythritol increased the biliary excretion of Cd, while the carboxyl-containing ones (EDTA and nitrilotriacetate) increased the urinary excretion of Cd. BAL was the most effective chelating agent, but there was also an increase in the renal concentration of Cd. However, when these chelating agents were administered 24 h after Cd injection (after the synthesis of metallothionein), only BAL increased the biliary excretion of Cd. Renal and hepatic Cd concentrations decreased concurrently after BAL treatment.

  8. On modeling of chemical stimulation of an enhanced geothermal system using a high pH solution with chelating agent

    SciTech Connect

    Xu, T.; Rose, P.; Fayer, S.; Pruess, K.

    2009-05-01

    Dissolution of silica and calcite in the presence of a chelating agent (NTA) at a high pH was successfully demonstrated in laboratory experiments using a high-temperature flow reactor. (Note that the term 'silica' used here includes amorphous silica, quartz, and silicate glass bead). The mineral dissolution and associated porosity enhancement in the experiments were reproduced by reactive transport modeling using TOUGHREACT. The chemical stimulation method was applied by numerical modeling to a field geothermal injection well system to investigate its effectiveness. Parameters applicable to the quartz monzodiorite unit at the Enhanced Geothermal Systems (EGS) site at Desert Peak (Nevada) were used. Results indicate that the injection of a high pH chelating solution results in dissolution of both calcite and plagioclase, while avoiding precipitation of calcite at high temperature conditions. Consequently reservoir porosity and permeability can be enhanced especially near the injection well. Injection at a lower temperature of 120 C (over 160 C in the base-case) results in a porosity increase that is smaller close to the injection point, but extends to a larger radial distance. A slower kinetic rate results in less aggressive mineral dissolution close to the injection point and larger extent along the flow path, which is favorable for chemical stimulation.

  9. Effect of long-term removal of iron from asbestos by desferrioxamine B on subsequent mobilization by other chelators and induction of DNA single-strand breaks.

    PubMed

    Chao, C C; Aust, A E

    1994-01-01

    The long-term removal of iron from crocidolite or amosite by desferrioxamine B (DF) at pH 7.5 or 5.0 was studied. Crocidolite or amosite (1 mg/ml) was suspended in 50 mM NaCl at pH 7.5 or 5.0 with the addition of 1 mM DF for up to 90 days. Although the rate of iron mobilization decreased with time, iron was continuously mobilized from both forms of asbestos at pH 5.0 or 7.5. The amount of iron mobilized from crocidolite was at least twice that mobilized from amosite at either pH. Iron was mobilized more rapidly from crocidolite at pH 5.0 than at 7.5 for the first 15 days, but at later times the amount being mobilized at pH 7.5 became equal to or slightly greater than that at 5.0. For amosite, the mobilization at pH 5.0 was always greater than that at pH 7.5. Next, the effect of iron removal from asbestos by DF on subsequent iron mobilization by a second chelator (EDTA or citrate) and on induction of DNA single-strand breaks (SSBs) was studied. Asbestos, treated for up to 15 days with DF at pH 7.5, was washed to remove ferrioxamine and excess DF, then incubated with EDTA or citrate (1 mM). The rates of iron mobilization from both forms of asbestos by a second chelator decreased as more and more iron was removed by DF. Induction of DNA SSBs also decreased, reflecting the unavailability of iron to catalyze the damage. The results suggest three things. First, if long-term mobilization of iron from asbestos occurs in vivo as has been observed in vitro, it may play a role in the long-term biological effects of asbestos. Second, more rapid mobilization of iron from asbestos fibers may occur when the fibers are phagocytized by cells and maintained in phagosomes where the pH is 4.0-5.0. Third, treatment of asbestos by iron chelators, such as DF, prior to exposure to cultured cells or whole animals, may reduce the biological effects of asbestos resulting from iron, but may not completely eliminate them.

  10. Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents.

    PubMed

    Tei, Lorenzo; Gugliotta, Giuseppe; Avedano, Stefano; Giovenzana, Giovanni B; Botta, Mauro

    2009-11-07

    The Ugi four-component reaction (Ugi 4CR) was exploited for the first time to obtain in a single synthetic step bifunctional ditopic chelators by using DOTA monoamide (DOTAMA) derivatives as amino and acid components. A number of ditopic systems in which the two DOTAMA units are connected by a central alpha-acylaminoamide group were synthesized by reacting different aldehydes, isocyanides and two DOTAMA chelates containing amino and acid functionalities. Variation of the components allows the insertion of another functional group into the alpha-acylaminoamide skeleton for further conjugation to biomolecules. The optimal reaction conditions were found by using methanol as solvent and ultrasound irradiation at a power of 60 W (20 kHz) for 3 h. The Gd(III) complexes of the dimeric ligands L1 and L2 (bearing a cyclohexyl ring and an octadecyl chain on the central alpha-acylaminoamide moiety, respectively) were fully characterized in aqueous media by relaxometric techniques with varying temperature and magnetic field strength. The relaxivity of Gd(2)L1 and Gd(2)L2 (in the aggregated form), at 20 MHz and 310 K, are 5.6 and 20.0 mM(-1) s(-1), respectively. The enhanced value found for Gd(2)L2 indicates that this lipophilic complex forms micelles at concentrations <0.1 mM. Finally, the binding of Gd(2)L2 to human serum albumin (HSA) was investigated by proton relaxometry, and the affinity constant of the complex and the relaxivity of the macromolecular adduct (r(1p)(b) = 38.1 mM(-1) s(-1); 20 MHz and 310 K) derived.

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

    PubMed

    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.

  12. Effect of Surface Modification by Chelating Agents on Fischer- Tropsch Performance of Co/SiO{sub 2} Catalysts

    SciTech Connect

    Bambal, Ashish S.; Kugler, Edwin L.; Gardner, Todd H.; Dadyburjor, Dady B.

    2013-11-14

    The silica support of a Co-based catalyst for Fischer-Tropsch (FT) synthesis was modified by the chelating agents (CAs) nitrilotriacetic acid (NTA) and ethylenediaminetetraacetic acid (EDTA). After the modification, characterization of the fresh and spent catalysts show reduced crystallite sizes, a better-dispersed Co₃O₄ phase on the calcined samples, and increased metal dispersions for the reduced samples. The CA-modified catalysts display higher CO conversions, product yields, reaction rates and rate constants. The improved FT performance of CA-modified catalysts is attributed to the formation of stable complexes with Co. The superior performance of the EDTA-modified catalyst in comparison to the NTA-modified catalyst is due to the higher affinity of the former for complex formation with Co ions.

  13. Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells.

    PubMed

    Hegde, Narasimha V; Jensen, Gordon L; Unger, Erica L

    2011-02-15

    Cell surface expression of the dopamine transporter (DAT) is determined by the relative rates of its internalization and recycling. Changes in the cellular labile iron pool (LIP) affect many cellular mechanisms including those that regulate DAT trafficking. In this study, we analyzed DAT expression and posttranslational modifications in response to changes in cellular iron in transfected neuroblastoma cells (N2a). Iron chelation by desferrioxamine (DFO) altered DAT protein levels by decreasing the stability of DAT mRNA. Increased phosphorylation and ubiquitination of this transporter protein following DFO treatment were also observed. Cellular iron depletion elevated protein levels of the early endosomal marker Rab5. Moreover, confocal microscopy studies showed increased localization of DAT into the endosomal compartment in DFO-treated cells compared to control. Together, these findings suggest that cellular iron depletion regulates DAT expression through reducing mRNA stability as well as an increasing in endocytosis.

  14. Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron

    PubMed Central

    Alta, Roxana Y. P.; Vitorino, Hector A.; Goswami, Dibakar; Liria, Cleber W.; Wisnovsky, Simon P.; Kelley, Shana O.

    2017-01-01

    Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity. They were relatively non toxic to A2780 cells (IC50 40–100 μM) and had good mitochondrial localization (Rr +0.45 –+0.68) as observed when labeled with carboxy-tetramethylrhodamine (TAMRA) In general, mtDFO caused only modest levels of mitochondrial DNA (mtDNA) damage. DFO-SS02 retained the antioxidant ability of the parent peptide, shown by the inhibition of mitochondrial superoxide formation. None of the compounds displayed cell cycle arrest or enhanced apoptosis. Taken together, these results indicate that mtDFO could be promising compounds for amelioration of the disease symptoms of iron overload in mitochondria. PMID:28178347

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

    PubMed

    Klosterman, Luke; Bettinger, Christopher J

    2016-12-22

    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 Fe(2+)/Fe(3+) 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.

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

    PubMed Central

    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

  17. Differential effect of buffer on the spin trapping of nitric oxide by iron chelates.

    PubMed

    Porasuphatana, S; Weaver, J; Budzichowski, T A; Tsai, P; Rosen, G M

    2001-11-01

    Nitric oxide synthase (NOS) generates nitric oxide (NO*) by the oxidation of l-arginine. Spin trapping in combination with electron paramagnetic resonance (EPR) spectroscopy using ferro-chelates is considered one of the best methods to detect NO* in real time and at its site of generation. The spin trapping of NO* from isolated NOS I oxidation of L-arginine by ferro-N-dithiocarboxysarcosine (Fe(DTCS)2) and ferro-N-methyl-d-glucamide dithiocarbamate (Fe(MGD)2) in different buffers was investigated. We detected NO-Fe(DTCS)2, a nitrosyl complex, resulting from the reaction of NO* and Fe(DTCS)2, in phosphate buffer. However, Hepes and Tris buffers did not allow formation of NO-Fe(DTCS)2. Instead, both of these buffers reacted with Fe2+, generating sparingly soluble complexes in the absence of molecular oxygen. Fe(DTCS)2 and Fe(MGD)2 were found to inhibit, to a small degree, NOS I activity with a greater effect observed with Fe(MGD)2. In contrast, Fe(MGD)2 was more efficient at spin trapping NO* from the lipopolysaccharide-activated macrophage cell line RAW264.7 than was Fe(DTCS)2. Data suggested that Fe(DTCS)2 and Fe(MGD)2 are efficient at spin trapping NO* but their maximal efficiency may be affected by experimental conditions.

  18. The novel mitochondrial iron chelator 5-((methylamino)methyl)-8-hydroxyquinoline protects against mitochondrial-induced oxidative damage and neuronal death.

    PubMed

    Mena, Natalia P; García-Beltrán, Olimpo; Lourido, Fernanda; Urrutia, Pamela J; Mena, Raúl; Castro-Castillo, Vicente; Cassels, Bruce K; Núñez, Marco T

    2015-08-07

    Abundant evidence indicates that iron accumulation, oxidative damage and mitochondrial dysfunction are common features of Huntington's disease, Parkinson's disease, Friedreich's ataxia and a group of disorders known as Neurodegeneration with Brain Iron Accumulation. In this study, we evaluated the effectiveness of two novel 8-OH-quinoline-based iron chelators, Q1 and Q4, to decrease mitochondrial iron accumulation and oxidative damage in cellular and animal models of PD. We found that at sub-micromolar concentrations, Q1 selectively decreased the mitochondrial iron pool and was extremely effective in protecting against rotenone-induced oxidative damage and death. Q4, in turn, preferentially chelated the cytoplasmic iron pool and presented a decreased capacity to protect against rotenone-induced oxidative damage and death. Oral administration of Q1 to mice protected substantia nigra pars compacta neurons against oxidative damage and MPTP-induced death. Taken together, our results support the concept that oral administration of Q1 is a promising therapeutic strategy for the treatment of NBIA.

  19. Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina

    PubMed Central

    Song, Delu; Song, Ying; Hadziahmetovic, Majda; Zhong, Yong; Dunaief, Joshua L.

    2012-01-01

    Oxidative stress plays a key role in the light damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). Since iron can promote oxidative stress, the iron chelator Deferiprone (DFP) was tested for protection against light-induced retinal degeneration. To accomplish this, A/J mice were treated with or without DFP in drinking water, and then were placed in constant bright white fluorescent light (10,000 lux) for 20 hours. Retinas were evaluated at several time points after light exposure. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal degeneration was assessed by histology 10 days after exposure to damaging white light. Two genes upregulated by oxidative stress, heme oxygenase 1 (Hmox1) and ceruloplasmin (Cp), as well as complement component 3 (C3) were quantified by RT-qPCR. Cryosections were immunolabeled for oxidative stress marker (nitrotyrosine), a microglial marker (Iba1) as well as both heavy (H) and light (L) ferritin. Light exposure resulted in substantial photoreceptor-specific cell death. Dosing with DFP protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of oxidative stress related genes and C3 were upregulated following light exposure and diminished by DFP treatment. Immunostaining for nitrotyrosine indicated that DFP reduced the nitrative stress caused by light exposure. Robust H/L-ferritin-containing microglial activation and migration to the outer retina occurred after light exposure and DFP treatment reduced microglial invasion. DFP is protective against light-induced retinal degeneration and has the potential to diminish oxidative stress in the retina. PMID:22579919

  20. Regeneration of Three-Way Automobile Catalysts using Biodegradable Metal Chelating Agent – S, S-Ethylenediamine Disuccinic Acid (S, S-EDDS)

    EPA Science Inventory

    Regeneration of the activity of three-way catalytic converters (TWCs) was tested for the first time using a biodegradable metal chelating agent (S, S. Ethylenediamine disuccinic acid (S, S-EDDS). The efficiency of this novel environmentally friendly solvent in removing various c...

  1. High performance liquid chromatography profiling of health-promoting phytochemicals and evaluation of antioxidant, anti-lipoxygenase, iron chelating and anti-glucosidase activities of wetland macrophytes

    PubMed Central

    Ooh, Keng-Fei; Ong, Hean-Chooi; Wong, Fai-Chu; Sit, Nam-Weng; Chai, Tsun-Thai

    2014-01-01

    Background: The phytochemistry and bioactivity of wetland macrophytes are underexplored. Plants are known as the natural sources of phytochemical beneficial to health. Objective: The objective of this study is to analyze the phytochemical profiles and bioactivities of 10 extracts prepared from different plant parts of wetland macrophytes Hanguana malayana, Ludwigia adscendens and Monochoria hastata. Materials and Methods: High performance liquid chromatography (HPLC) was used to analyze the phytochemical profile of the extracts. Antioxidant assay such as 2,2-diphenyl-1-picrylhydrazyl, nitric oxide (NO) radical scavenging activity and ferric reducing antioxidant power were performed. Bioactivity assays carried out were anti-lipoxygenase, anti-glucosidase, and iron chelating. Results: Leaf extract of L. adscendens had the highest 2,2-diphenyl-1-picrylhydrazyl (half of maximal effective concentration [EC50] =0.97 mg/mL) and NO (EC50 = 0.31 mg/mL) scavenging activities. The extract also exhibited the highest iron chelating (EC50 = 3.24 mg/mL) and anti-glucosidase (EC50 = 27.5 μg/mL) activities. The anti-glucosidase activity of L. adscendens leaf extract was comparable or superior to those of acarbose, myricetin and quercetin. Correlation between iron chelating and radical scavenging activities among the extracts implies the presence of dual-function phytoconstituents with concurrent iron chelating and radical scavenging activities. HPLC analysis revealed the presence of p-coumaric acid (p-CA), gallic acid (GA) and myricetin in all or most extracts. M. hastata fruit and leaf extracts had the highest p-hydroxybenzoic acid content. Antioxidant and anti-glucosidase activities of the extracts were correlated with p-CA, GA, and myricetin contents. Conclusion: Our study demonstrated that wetland macrophytes H. malayana, L. adscendens and M. hastata are potential sources of health-promoting phytochemicals with potent therapeutically-relevant bioactivities. PMID:25298659

  2. 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.

    PubMed

    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.

  3. Enhancement of Phloem Exudation from Cut Petioles by Chelating Agents 1

    PubMed Central

    King, R. W.; Zeevaart, J. A. D.

    1974-01-01

    The photosynthetic assimilates in leaves of Perilla crispa attached to the plant were labeled by treating the leaves with 14CO2. When subsequently detached, these leaves exuded a negligible amount of radioactivity from the cut petiole into water. Ethylenediaminetetraacetate (EDTA), citric acid, and ethyleneglycol-bis (β-aminoethyl ether) N,N′-tetraacetate greatly increased exudation of labeled assimilates into a solution bathing the petioles. The optimal concentration of EDTA was 20 mm, and maximal exudation took place between 2 and 4 hours after excision. Up to 22% of the radioactivity fixed in the leaf was exuded into an EDTA solution as compared to an export of 38% from attached leaves. The amount of radioactivity in the exudate was much reduced at low temperature. Presence of EDTA was required in the collecting solution for only 1 to 2 hours; upon transfer to water, exudation continued as in continuous presence of EDTA. Ca2+ completely inhibited the effect of EDTA. Anatomical studies indicated that callose formation on the sieve plates near the cut surface of the petioles was less in leaves on EDTA than on water. More than 95% of the radioactivity exuded by detached leaves was present in the sugars verbascose, stachyose, raffinose, and sucrose, which are translocated in the phloem of Perilla. Labeled glucose, fructose, and galactinol were detected in the leaf blade and petiole, but not in exudates. The addition of EDTA to a solution bathing the petiole of detached leaves of Chenopodium rubrum and Pharbitis nil also increased the exudation of labeled assimilates. In these two species, label appeared only in a compound that cochromatographed with sucrose. It is concluded that the radioactive products in the solution are actually exuded by the phloem. Possibly EDTA chelates Ca2+ that otherwise participates in the reactions that seal cut phloem. Images PMID:16658661

  4. Reversible immobilization of BSA on Cu-chelated PAMAM dendrimer modified iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Demir, M.; Şenel, M.; Baykal, A.

    2014-09-01

    In this study, polyamidoamine (PAMAM) dendrimer coated superparamagnetite nanoparticles were synthesized by growing of PAMAM on amino-silane coated iron oxide nanoparticles. The PAMAM modified superparamagnetite nanoparticles were used as reversible protein immobilization host materials. During the reversible immobilization studies the effect of different metal ions such as; Cu+2, Zn+2, Co+2, Ni+2 on immobilization efficiency of BSA were evaluated. The maximum BSA adsorption capacity of the PAMAM-MNP- Cu+2 beads was observed to be 52.84 mg/g (BSA/PAMAM-MNP) at pH 7.0. Various characteristics of immobilized BSA such as; effect of generation, effect of pH, BSA concentration, temperature, salt concentration and reusability of PAMAM-MNP were evaluated.

  5. Lanthanide oleates: chelation, self-assembly, and exemplification of ordered nanostructured colloidal contrast agents for medical imaging.

    PubMed

    Liu, Guozhen; Conn, Charlotte E; Drummond, Calum J

    2009-12-10

    Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T(1)) and transverse (T(2)) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.

  6. Reactions of aqueous iron-DFOB (desferrioxamine B) complexes with flavin mononucleotide in the absence of strong iron(II) chelators

    NASA Astrophysics Data System (ADS)

    Kim, Dongwook; Duckworth, Owen W.; Strathmann, Timothy J.

    2010-03-01

    The mechanisms controlling microbial uptake of Fe III-siderophore complexes and subsequent release of the metal for cellular use have been extensively studied in recent years. Reduction of the Fe III center is believed to be necessary to labilize the coordinated Fe and facilitate exchange with cellular ligands. Previous studies report reduction of Fe III-DFOB by various reducing agents in solutions containing Fe II-chelating colorimetric agents for monitoring reaction progress, but the importance of these findings is unclear because the colorimetric agents themselves stabilize and enhance the reactions being monitored. This study examines the reduction of Fe III complexes with DFOB (desferrioxamine B), a trihydroxamate siderophore, by the fully reduced hydroquinone form of flavin mononucleotide (FMN HQ) in the absence of strong Fe II-chelating agents, and Fe redox cycling in solutions containing DFOB and oxidized and reduced FMN species. Experimental results demonstrate that the rate and extent of Fe III-DFOB reduction is strongly dependent on pH and FMN HQ concentration. At pH ⩾ 5, incomplete Fe III reduction is observed due to two processes that re-oxidize Fe II, namely, the autodecomposition of Fe II-DFOB complexes (Fe II oxidation is coupled with reduction of a protonated hydroxamate moiety) and reaction of Fe II-DFOB complexes with the fully oxidized flavin mononucleotide product (FMN OX). Chemical speciation-dependent kinetic models for the forward reduction process and both reverse Fe II oxidation processes are developed, and coupling kinetic models for all three Fe redox processes leads to successful predictions of steady-state Fe II concentrations observed over a range of pH conditions in the presence of excess FMN HQ and FMN OX. The observed redox reactions are also in agreement with thermodynamic constraints imposed by the combination of Fe III/Fe II and FMN OX/FMN HQ redox couples. Quantitative comparison between kinetic trends and changing Fe

  7. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects.

    PubMed

    Blanusa, Maja; Varnai, Veda M; Piasek, Martina; Kostial, Krista

    2005-01-01

    The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

  8. Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning.

    PubMed

    Carvalho, Cristina M L; Lu, Jun; Zhang, Xu; Arnér, Elias S J; Holmgren, Arne

    2011-01-01

    Mercury toxicity is a highly interesting topic in biomedicine due to the severe endpoints and treatment limitations. Selenite serves as an antagonist of mercury toxicity, but the molecular mechanism of detoxification is not clear. Inhibition of the selenoenzyme thioredoxin reductase (TrxR) is a suggested mechanism of toxicity. Here, we demonstrated enhanced inhibition of activity by inorganic and organic mercury compounds in NADPH-reduced TrxR, consistent with binding of mercury also to the active site selenolthiol. On treatment with 5 μM selenite and NADPH, TrxR inactivated by HgCl(2) displayed almost full recovery of activity. Structural analysis indicated that mercury was complexed with TrxR, but enzyme-generated selenide removed mercury as mercury selenide, regenerating the active site selenocysteine and cysteine residues required for activity. The antagonistic effects on TrxR inhibition were extended to endogenous antioxidants, such as GSH, and clinically used exogenous chelating agents BAL, DMPS, DMSA, and α-lipoic acid. Consistent with the in vitro results, recovery of TrxR activity and cell viability by selenite was observed in HgCl(2)-treated HEK 293 cells. These results stress the role of TrxR as a target of mercurials and provide the mechanism of selenite as a detoxification agent for mercury poisoning.

  9. Nanovectors for anticancer agents based on superparamagnetic iron oxide nanoparticles

    PubMed Central

    Douziech-Eyrolles, Laurence; Marchais, Hervé; Hervé, Katel; Munnier, Emilie; Soucé, Martin; Linassier, Claude; Dubois, Pierre; Chourpa, Igor

    2007-01-01

    During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug. PMID:18203422

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

    PubMed

    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

  11. Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos.

    PubMed

    Kamp, D W; Israbian, V A; Yeldandi, A V; Panos, R J; Graceffa, P; Weitzman, S A

    1995-01-01

    Reactive oxygen species, especially iron-catalyzed hydroxyl radicals (.OH) are implicated in the pathogenesis of asbestos-induced pulmonary toxicity. We previously demonstrated that phytic acid, an iron chelator, reduces amosite asbestos-induced .OH generation, DNA strand break formation, and injury to cultured pulmonary epithelial cells (268[1995, Am. J. Physiol.(Lung Cell. Mol. Physiol.) 12:L471-480]). To determine whether phytic acid diminishes pulmonary inflammation and fibrosis in rats after a single intratracheal (it) instillation of amosite asbestos, Sprague-Dawley rats were given either saline (1 ml), amosite asbestos (5 mg; 1 ml saline), or amosite treated with phytic acid (500 microM) for 24 hr and then instilled. At various times after asbestos exposure, the rats were euthanized and the lungs were lavaged and examined histologically. A fibrosis score was determined from trichrome-stained specimens. As compared to controls, asbestos elicited a significant pulmonary inflammatory response, as evidence by an increase (approximately 2-fold) in bronchoalveolar lavage (BAL) cell counts at 1 wk and the percentage of BAL neutrophils (PMNs) and giant cells at 2 wk (0.1 vs 6.5% and 1.3 vs 6.1%, respectively; p < 0.05). Asbestos significantly increased the fibrosis score at 2 wk (0 +/- 0 vs 5 +/- 1; p < 0.05). The inflammatory and fibrotic changes were, as expected, observed in the respiratory bronchioles and terminal alveolar duct bifurcations. The increased percentage of BAl PMNs and giant cells persisted at 4 wk, as did the fibrotic changes. Compared to asbestos alone, phytic acid-treated asbestos elicited significantly less BAL PMNs (6.5 vs 1.0%; p < 0.05) and giant cells (6.1 vs 0.2%; p < 0.05) and caused significantly less fibrosis (5 vs 0.8; p < 0.05) 2 wk after exposure. We conclude that asbestos causes pulmonary inflammation and fibrosis in rats after it instillation and that phytic acid reduces these effects. These data support the role of iron

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

    SciTech Connect

    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.

  13. Hexadentate bispidine derivatives as versatile bifunctional chelate agents for copper(II) radioisotopes.

    PubMed

    Juran, Stefanie; Walther, Martin; Stephan, Holger; Bergmann, Ralf; Steinbach, Jörg; Kraus, Werner; Emmerling, Franziska; Comba, Peter

    2009-02-01

    The preparation and use of bispidine derivatives (3,7-diazabicyclo[3.3.1]nonane) as chelate ligands for radioactive copper isotopes for diagnosis (64Cu) or therapy (67Cu) are reported. Starting from the hexadentate bispidine-based bis(amine)tetrakis(pyridine) ligand 1 with a keto and two ester substituents, the corresponding mono-ol 2 and two dicarboxylic acid derivatives 3 and 5 have been synthesized. A range of techniques, including single-crystal X-ray structure analysis, UV/vis spectroscopy, cyclic voltammetry, thin-layer- (TLC), and high-performance liquid chromatography (HPLC), have been used to characterize the structure and stability of the copper(II)-bispidine complexes. A rapid formation (within 1 min) of stable copper(II)-bispidine complexes under mild conditions (ambient temperature, aqueous solution) has been observed. Challenge experiments of these complexes in the presence of a high excess of competing ligands, such as glutathione, cyclam, or superoxide dismutase (SOD), as well as in rat plasma, gave no evidence of demetalation or transchelation. The bifunctional bispidine derivative 5 can be readily functionalized with biologically active molecules at the pendant carboxylate groups. The coupling of a bombesin analogue betahomo-Glu-betaAla-betaAla-[Cha(13),Nle(14)]BBN(7-14), by condensation of a carboxylate of the bispidine backbone with the N-terminus of the peptide produced the bifunctional ligand 6. The radiocopper(II) complex of this bombesin-bispidine conjugate has a considerable hydrophilicity (log D(o/w) < -2.4), and this leads to a very fast blood clearance (blood: 0.28 +/- 0.02 SUV, 1 h p.i.), low liver tissue accumulation (liver: 1.20 +/- 0.27 SUV, 1 h p.i.), and rapid renal-urinary excretion (kidneys: 6.06 +/- 2.96 SUV, 1 h p.i.) as shown by biodistribution studies of 64Cu-6 in Wistar rats. Preliminary in vivo studies of 64Cu-6 in NMRI nu/nu mice, bearing the human prostate tumor PC-3 showed an accumulation of the conjugate in the tumor (2

  14. Ion paired chromatography of iron (II,III), nickel (II) and copper (II) as their 4,7-Diphenyl-1,10-phenanthroline chelates.

    PubMed

    Mudasir; Yoshioka, N; Inoue, H

    1997-07-01

    A reversed phase ion-paired chromatographic method that can be used to determine trace amounts of iron (II,III), nickel (II) and copper (II) was developed and applied to the determination of iron (II) and iron (III) levels in natural water. The separation of these metal ions as their 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline) chelates on an Inertsil ODS column was investigated by using acetonitrile-water (80/20, v/v) containing 0.06 M perchloric acid as mobile phase and diode array spectrophotometric detection at 250-650 nm. Chromatographic parameters such as composition of mobile phase and concentration of perchloric acid in mobile phase were optimized. The calibration graphs of iron (II), nickel (II) and copper (II) ions were linear (r > 0.991) in the concentration range 0-0.5, 0-2.0 and 0-4.0 mug ml(-1), respectively. The detection limit of iron (II), nickel (II) and copper (II) were 2.67, 5.42 and 18.2 ng ml(-1) with relative standard deviation (n = 5) of 3.11, 5.81 and 7.16% at a concentration level of 10 ng ml(-1) for iron (II) and nickel (II) and 25 ng ml(-1) for copper (II), respectively. The proposed method was applied to the determination of iron(II) and iron(III) in tap water and sea water samples without any interference from other common metal ions.

  15. A comparative study on the enhancement efficacy of specific and non-specific iron chelators for protoporphyrin IX production and photosensitization in HaCat cells.

    PubMed

    Xia, Yumin; Huang, Yingying; Lin, Longde; Liu, Xiaoming; Jiang, Shan; Xiong, Layuan

    2009-12-01

    The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT). The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular protoporphyrin IX (PpIX) was detected by high performance liquid chromatography (HPLC), and the fluorescence of PpIX was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpIX and the fluorescent density of PpIX, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpIX level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpIX production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.

  16. Additive Neuroprotective Effects of the Multifunctional Iron Chelator M30 with Enriched Diet in a Mouse Model of Amyotrophic Lateral Sclerosis.

    PubMed

    Golko-Perez, Sagit; Mandel, Silvia; Amit, Tamar; Kupershmidt, Lana; Youdim, Moussa B H; Weinreb, Orly

    2016-02-01

    Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motoneuron system, involving various abnormalities, such as mitochondrial dysfunction, oxidative stress, transitional metal accumulation, neuroinflammation, glutamate excitotoxicity, apoptosis, decreased supply of trophic factors, cytoskeletal abnormalities, and extracellular superoxide dismutase (SOD)-1 toxicity. These multiple disease etiologies implicated in ALS gave rise to the perception that future therapeutic approaches for the disease should be aimed at targeting multiple pathological pathways. In line with this view, we have evaluated in the current study the therapeutic effects of low doses of the novel multifunctional monoamine oxidase (MAO) inhibitor/iron-chelating compound, M30 in combination with high Calorie Energy supplemented Diet (CED) in the SOD1-G93A transgenic mouse model of ALS. Our results demonstrated that the combined administration of M30 with CED produced additive neuroprotective effects on motor performance and increased survival of SOD1-G93A mice. We also found that both M30 and M30/CED regimens caused a significant inhibition of MAO-A and -B activities and decreased the turnover of dopamine in the brain of SOD1-G93A mice. In addition, M30/CED combined treatment resulted in a significant increase in mRNA expression levels of various mitochondrial biogenesis and metabolism regulators, such as peroxisome proliferator-activated receptor-γ (PPARγ)-co activator 1 alpha (PGC-1α), PPARγ, uncoupling protein 1, and insulin receptor in the gastrocnemius muscle of SOD1-G93A mice. These results suggest that a combination of drug/agents with different, but complementary mechanisms may be beneficial in the treatment of ALS.

  17. Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.

    PubMed

    Renaud, Stéphanie; Corcé, Vincent; Cannie, Isabelle; Ropert, Martine; Lepage, Sylvie; Loréal, Olivier; Deniaud, David; Gaboriau, François

    2015-08-01

    Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cancer.

  18. Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox.

    PubMed

    Viprakasit, Vip; Ibrahim, Hishamshah; Ha, Shau-Yin; Ho, Phoebe Joy; Li, Chi-Kong; Chan, Lee-Lee; Chiu, Chang-Fang; Sutcharitchan, Pranee; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Xue, Hong-Ling; Bowden, Donald K; Lin, Kai-Hsin

    2011-03-01

    Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

  19. Beneficial Effects of Multitarget Iron Chelator on Central Nervous System and Gastrocnemius Muscle in SOD1(G93A) Transgenic ALS Mice.

    PubMed

    Golko-Perez, Sagit; Amit, Tamar; Youdim, Moussa B H; Weinreb, Orly

    2016-08-01

    Accumulation of evidence has demonstrated high levels of iron in the central nervous system of both sporadic and familial amyotrophic lateral sclerosis (ALS) patients and in ALS mouse models. In accordance, iron chelation therapy was found to exert beneficial effects on ALS mice. Our group has designed and synthesized series of multifunctional non-toxic, brain permeable iron-chelating compounds for neurodegenerative diseases. Recent study has shown that co-administration of one of these drugs, VAR10303 with high calorie/energy-supplemented diet (VAR-ced), initiated after the appearance of disease symptoms improved motor performance, extended survival, and attenuated iron accumulation and motoneuron loss in SOD1(G93A) mice. Since VAR was found to exert diverse pharmacological properties associated with mitochondrial biogenesis in the gastrocnemius (GNS) muscle, we further assessed in the current study the impact of VAR-ced on additional neurorescue-associated molecular targets in the GNS and frontal cortex in SOD1(G93A) mice. The results show that VAR-ced treatment upregulated the expression of various HIF-1α-target glycolytic genes and elevated the levels of Bcl-2, neurotrophic factors, and AKT/GSK3β signaling in the GNS and frontal cortex of SOD1(G93A) mice, suggesting that these protective regulatory parameters regulated by VAR-ced treatment may be associated with the beneficial effects of the drug observed on ALS mice.

  20. Effects of iron glycine chelate on growth, tissue mineral concentrations, fecal mineral excretion, and liver antioxidant enzyme activities in broilers.

    PubMed

    Ma, W Q; Sun, H; Zhou, Y; Wu, J; Feng, J

    2012-11-01

    The study was conducted to determine the effects of iron glycine chelate (Fe-Gly) on growth, tissue mineral concentrations, fecal mineral excretion, and liver antioxidant enzyme activities in broilers. A total of 360 1-day-old commercial broilers (Ross × Ross) were randomly allotted to six dietary treatments with six replications of ten chicks per replicate. Broilers were fed a control diet with no Fe supplementation, while five other treatments consisted of 40, 80, 120, and 160 mg Fe/kg diets from Fe-Gly, and 160 mg Fe/kg from ferrous sulfate, respectively. After a 42-day feeding trial, the results showed that 120 and 160 mg Fe/kg as Fe-Gly improved the average daily gain (P < 0.05) and average daily feed intake (P < 0.05) of broilers (4-6 weeks). Addition with 120 and 160 mg Fe/kg from Fe-Gly and 160 mg Fe/kg from FeSO(4) increased Fe concentration in serum (P < 0.05), liver (P < 0.05), breast muscle (P < 0.05), tibia (P < 0.05), and feces (P < 0.01) at 21 and 42 days. There were linear responses to the addition of Fe-Gly from 0 to 160 mg/kg Fe on Fe concentration in serum (21 days, P = 0.005; 42 days, P = 0.001), liver (P = 0.001), breast muscle (P = 0.001), tibia (P = 0.001), and feces (21 days, P = 0.011; 42 days, P = 0.032). Liver Cu/Zn superoxide dismutase activities of chicks were increased by the addition of 80, 120, and 160 mg Fe/kg as Fe-Gly to diets at 42 days. There were no differences in liver catalase activities of chicks among the treatments (P > 0.05). This study indicates that addition with Fe-Gly could improve growth performance and iron tissue storage and improves the antioxidant status of broiler chickens.

  1. Freeze-dried stallion spermatozoa: evaluation of two chelating agents and comparative analysis of three sperm DNA damage assays.

    PubMed

    Olaciregui, M; Luño, V; Martí, J I; Aramayona, J; Gil, L

    2016-11-01

    During the freeze-drying procedure, sperm DNA might become damaged by both freezing and drying stresses. Sperm DNA status can be detected using well-established assays; however, most techniques are expensive and involve elaborate protocols and equipment. Indirect assessments can provide alternative strategies. The objective of this study was to compare a simple test of DNA status using Diff-Quik (DQ) with two established procedures: acridine orange test (AOT) and sperm chromatin dispersion (SCD) on freeze-dried (FD) stallion spermatozoa. Ejaculated spermatozoa from three stallions were freeze-dried in basic medium supplemented with two different chelating agents: EGTA or EDTA. After rehydration, the spermatozoa were subjected to DNA damage detection using a SCDt, AOT and DQ stain simultaneously. The results showed that the DNA damage levels in the EGTA group were significantly lower than those in the EDTA group. AOT detected a significantly higher proportion of spermatozoa with fragmented DNA than DQ and SCD. The results of the SCD test and DQ stain exhibited a significant positive correlation for DNA fragmentation (r = 0.528), whereas a negative correlation was observed between SCD, DQ and AOT (r = -0.134 and r = -0.332 respectively). The present study shows that both the SCD test and DQ assay are effective methods for detecting FD stallion sperm DNA fragmentation, whereas using of AOT is questionable.

  2. Sequential application of chelating agents and innovative surfactants for the enhanced electroremediation of real sediments from toxic metals and PAHs.

    PubMed

    Hahladakis, John N; Lekkas, Nikolaos; Smponias, Andreas; Gidarakos, Evangelos

    2014-06-01

    This study focused on the sequential application of a chelating agent (citric acid) followed by a surfactant in the simultaneous electroremediation of real contaminated sediments from toxic metals and Polycyclic Aromatic Hydrocarbons (PAHs). Furthermore, the efficiency evaluation of two innovative non-ionic surfactants, commercially known as Poloxamer 407 and Nonidet P40, was investigated. The results indicated a removal efficacy of approximately 43% and 48% for the summation of PAHs (SUM PAHs), respectively for the aforementioned surfactants, much better than the one obtained by the use of Tween 80 (nearly 21%). Individual PAHs (e.g. fluorene) were removed in percentages that reached almost 84% and 92% in the respective electrokinetic experiments when these new surfactants were introduced. In addition, the combined-enhanced sequential electrokinetic treatment with citric acid improved dramatically the removal of Zn and As, compared to the unenhanced run, but did not favor the other toxic metals examined. Since no improvement in metal removal percentages occurred when Tween 80 was used, significant contribution to this matter should also be attributed to the solubilization capacity of these innovative, in electrokinetic remediation, non-ionic surfactants.

  3. Amelioration of metal-induced toxicity in Caenorhabditis elegans: utility of chelating agents in the bioremediation of metals.

    PubMed

    Harrington, James M; Boyd, Windy A; Smith, Marjolein V; Rice, Julie R; Freedman, Jonathan H; Crumbliss, Alvin L

    2012-09-01

    The presence of toxic amounts of transition metals in the environment may originate from a range of human activities and natural processes. One method for the removal of toxic levels of metals is through chelation by small molecules. However, chelation is not synonymous with detoxification and may not affect the bioavailability of the metal. To test the bioavailability of chelated metals in vivo, the effects of several metal/chelator combinations were tested in the environmentally relevant organism Caenorhabditis elegans. The effect of metal exposure on nematode growth was used to determine the toxicity of cadmium, copper, nickel, and zinc. The restoration of growth to levels observed in nonexposed nematodes was used to determine the protective effects of the polydentate chelators: acetohydroxamic acid (AHA), cyclam, cysteine, calcium EDTA, desferrioxamine B, 1,2-dimethyl,3-hydroxy,4-pyridinone, and histidine. Cadmium toxicity was removed only by EDTA; copper toxicity was removed by all of the chelators except AHA; nickel toxicity was removed by cyclam, EDTA, and histidine; and zinc toxicity was removed by only EDTA. These results demonstrate the utility of polydentate chelators in the remediation of metal-contaminated systems. They also demonstrate that although the application of a chelator to metal contaminants may be effective, binding alone cannot be used to predict the level of remediation. Remediation depends on a number of factors, including metal complex speciation in the environment.

  4. Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.

    PubMed

    Egeli, A K; Framstad, T

    1998-02-01

    The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the

  5. Chelation in metal intoxication--Principles and paradigms.

    PubMed

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

    2015-01-01

    The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment 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.

  6. Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.

    PubMed

    Wei, He; Bruns, Oliver T; Kaul, Michael G; Hansen, Eric C; Barch, Mariya; Wiśniowska, Agata; Chen, Ou; Chen, Yue; Li, Nan; Okada, Satoshi; Cordero, Jose M; Heine, Markus; Farrar, Christian T; Montana, Daniel M; Adam, Gerhard; Ittrich, Harald; Jasanoff, Alan; Nielsen, Peter; Bawendi, Moungi G

    2017-02-28

    Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.

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

    PubMed

    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.

  8. An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms.

    PubMed

    Breccia, Massimo; Voso, Maria Teresa; Aloe Spiriti, Maria Antonietta; Fenu, Susanna; Maurillo, Luca; Buccisano, Francesco; Tafuri, Agostino; Alimena, Giuliana

    2015-05-01

    Iron chelation therapy can improve hematopoiesis in myelodysplastic syndromes. Only few studies showed hematologic improvement with deferoxamine, and the erythroid responses were correlated with good compliance to long-term treatment. Indeed, single-case reports and data from clinical trials testing the efficacy of deferasirox reported hematologic improvements with varying rates of response in different lineages. Overall, about 760 myelodysplastic syndrome (MDS) patients with iron overload receiving deferasirox were included in six different studies, and an increase in hemoglobin level was reported to range from 6 to 44.5%, an increase in platelet count from 13 to 61%, and in neutrophil count from 3 to 76%. In all the published studies, hematologic improvements were not related to serum ferritin or to non-total binding iron changes; indeed, other pathways were indicated as possible pathogenetic mechanisms, such as decreased NF-kB activity, modulation of mTOR signalling, and reduced reactive oxygen species. The aims of this review are to provide all available information relating clinical and hematologic changes after chelation therapy and to discuss potential mechanisms involved in such responses.

  9. Plant mechanisms of siderophore-iron utilization

    SciTech Connect

    Crowley, D.E.

    1986-01-01

    Mechanisms of siderophore iron-utilization by plants were examined to determine whether plants have direct mechanisms for acquiring iron from microbially-produced hydroxamate siderophores or simply take up inorganic iron in equilibrium with the chelate (shuttle mechanism). Experiments were designed to determine whether the monocot plant species, oat (Avena sativa L. cv. Victory) could acquire iron from ferrichrome under hydroponic conditions in which iron uptake was most likely to occur by direct use of the chelating agent. Ten-day-old iron-deficient seedlings, grown in aerated Hoagland's nutrient solution (minus iron) buffered at pH 7.4 with CaCO/sub 3/, were placed in fresh nutrient solution containing 10/sup -7.4/M radioactive /sup 55/FeCl/sub 3/ (23.7 mCi/mg) with the synthetic chelate, EDDHA (10..pi../sup 5/M), ferrichrome (10/sup -5/M), or with no chelate. After 6 days, shoot content of /sup 55/Fe in shoots of plants provided with ferrichrome was 100-fold greater than that in shoots of plants provided with EDDHA. Therefore iron uptake by oat under these conditions not only indicates direct use of ferrichrome, but also suggest that oat may be better able to acquire iron from siderophores than from synthetic chelates. One possible mechanism for direct use of chelating agents, may involve siderophore binding sites on the plasmalemma of root cortical cells where iron is split from the chelate by enzymatic reduction of ferric to ferrous iron. To demonstrate hypothesized siderophore binding sites on oat roots, experiments examined possible competition for presumed siderophore binding sites by an inert analog of ferrichrome constructed by irreversible chelation with chromium.

  10. Effect of the ultrasound-Fenton oxidation process with the addition of a chelating agent on the removal of petroleum-based contaminants from soil.

    PubMed

    Li, Ying; Li, Fangmin; Li, Fanxiu; Yuan, Fuqian; Wei, Pingfang

    2015-12-01

    The effects of ultrasonic irradiation, the chelating agent modified Fenton reaction, and a combination of ultrasound and the Fenton method in removing petroleum contaminants from a soil were studied. The results showed that the contaminant removal rate of the Fenton treatment combined with an oxalic acid chelating agent was 55.6% higher than that without a chelating agent. The average removal rate of the contaminants using the ultrasound-Fenton treatment was 59.0% higher than that without ultrasonic treatment. A combination of ultrasound and an Fe(2+)/Fe(3+)-oxalate complex-modified Fenton reagent resulted in significantly higher removal rates of n-alkanes (C(n)H(2n+2), n < 28), isoprenoid hydrocarbons, aromatic hydrocarbons, and saturated polycyclic terpenes compared with the ultrasound treatment alone or the Fenton method. The Fenton reaction and the ultrasound-Fenton treatment can unselectively remove multiple components of residual hydrocarbons and a number of benzene rings in polycyclic aromatic hydrocarbons. The chemistry of the heterocyclic compounds and the position and number of substituents can affect the degradation process.

  11. Development of Iron Doped Silicon Nanoparticles as Bimodal Imaging Agents

    PubMed Central

    Singh, Mani P.; Atkins, Tonya M.; Muthuswamy, Elayaraja; Kamali, Saeed; Tu, Chuqiao; Louie, Angelique Y.; Kauzlarich, Susan M.

    2012-01-01

    We demonstrate the synthesis of water-soluble allylamine terminated Fe doped Si (SixFe) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single source iron containing precursor, Na4Si4 with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH4Br to produce hydrogen terminated SixFe nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation. Transmission electron microscopy (TEM) indicates that the average particle diameter is ~3.0±1.0 nm. The Si5Fe nanoparticles show strong photoluminescence quantum yield in water (~ 10 %) with significant T2 contrast (r2/r1value of 4.31). Electron paramagnetic resonance (EPR) and Mössbauer spectroscopies indicate that iron in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using the resazurin assay on HepG2 liver cells indicates that the particles have minimal toxicity. PMID:22616623

  12. Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents.

    PubMed

    Miller, Marvin J; Zhu, Helen; Xu, Yanping; Wu, Chunrui; Walz, Andrew J; Vergne, Anne; Roosenberg, John M; Moraski, Garrett; Minnick, Albert A; McKee-Dolence, Julia; Hu, Jingdan; Fennell, Kelley; Kurt Dolence, E; Dong, Li; Franzblau, Scott; Malouin, Francois; Möllmann, Ute

    2009-02-01

    Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the "microbial war", extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

  13. The protective role of iron chelation and zinc supplements in atherosclerosis induced in New Zealand white rabbits: A nuclear microscopy study

    NASA Astrophysics Data System (ADS)

    Ren, M. Q.; Rajendran, R.; Pan, N.; Huat, B. T. K.; Halliwell, B.; Watt, F.

    2005-04-01

    The protective properties of iron chelator desferal and zinc supplements on atherosclerosis induced in New Zealand white rabbits were investigated using nuclear microscopy, incorporating particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and scanning transmission ion microscopy (STIM). Firstly, we examined the effects of the desferal (desferrioxamine - a chelator which forms a stable complex with ferric iron) on atherosclerosis progression and lesion iron content in cholesterol-fed New Zealand white rabbits. Rabbits were fed with a 1% w/w cholesterol diet (HFD - high fat diet) for either 8 weeks (with the last 5 weeks injected daily with desferal), or for 12 weeks (with the last 9 weeks injected with desferal). Controls were injected with saline. A significant reduction in average lesion area (p = 0.038) was observed in the 12-week treated animals as compared with the 12-week controls. The average lesion iron level of the 12 week treated animals (58 ppm dry weight) was significantly lower (p = 0.03) than for the 12-week control animals (95 ppm dry weight). No reduction in lesion area or iron content was observed in the 8 week treated animals compared with controls, and no change in lesion zinc concentration was observed for either group. This data is consistent with the concept that iron contributes to the early stages in the development of atherosclerosis and that removal of iron from the lesion retards the progression of the disease. Secondly, the effect of zinc supplements on atherosclerotic lesion growth was examined. The rabbits in the test group received a 1% w/w cholesterol diet with Zn supplements for 8 weeks and the rabbits in the control group were fed only with a 1% w/w cholesterol diet for the same period of time. Lesion area analyses using light microscopy showed that the average lesion area was 1.0 mm2 for the test models compared with 3.0 mm2 for the control group models (p = 0.0045). Elemental analysis of the lesion

  14. Evaluation of the efficiency of DTPA and other new chelating agents for removing neptunium from target organs.

    PubMed

    Paquet, F; Metivier, H; Poncy, J L; Burgada, R; Bailly, T

    1997-05-01

    Diethylenetriamine pentaacetic acid (DTPA) has been tested with 8 other new chelators for neptunium decorporation after systemic contamination in the rat. The ligands were injected intravenously at a dosage of 30 mumol kg-1 and the animals killed 24 h later. The results show that none of the chelators tested was efficient in removing significant amounts of the radionuclide from the body. In order to understand why these chelators were ineffective, in vitro approaches have since been developed in which high concentrations of DTPA were added to Np-bearing ligands in the blood, liver and skeleton. The main conclusions were that under our experimental conditions neptunium was not chelatable after its organ deposition.

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

    PubMed

    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.

  16. Synthesis, antioxidant activities of the nickel(II), iron(III) and oxovanadium(IV) complexes with N2O2 chelating thiosemicarbazones.

    PubMed

    Bal-Demirci, Tülay; Sahin, Musa; Ozyürek, Mustafa; Kondakçı, Esin; Ulküseven, Bahri

    2014-05-21

    The nickel(II), iron(III) and oxovanadium(IV) complexes of the N2O2 chelating thiosemicarbazones were synthesized using 4-hydroxysalicyladehyde-S-methylthiosemicarbazone and R1-substitute-salicylaldehyde (R1: 4-OH, H) in the presence of Ni(II), Fe(III), VO(IV) ions by the template reaction. The structures of the thiosemicarbazone complexes were characterized by FT-IR, (1)H NMR, elemental, ESI-MS and APCI-MS analysis. The synthesized compounds were screened for their antioxidant capacity by using the cupric reducing antioxidant capacity (CUPRAC) method. Trolox equivalent antioxidant capacity (TEAC) of iron(III) complex, 1c, was measured to be higher than that of the other complexes. Other parameters of antioxidant activity (scavenging effects on •OH, O2(•-) and H2O2) of these compounds were also determined. All the compounds have shown encouraging ROS scavenging activities.

  17. Numerical simulation study of silica and calcite dissolution around a geothermal well by injecting high pH solutions with chelating agent.

    SciTech Connect

    Xu, Tianfu; Rose, Peter; Fayer, Scott; Pruess, Karsten

    2009-02-01

    Dissolution of silica, silicate, and calcite minerals in the presence of a chelating agent (NTA) at a high pH has been successfully performed in the laboratory using a high-temperature flow reactor. The mineral dissolution and porosity enhancement in the laboratory experiment has been reproduced by reactive transport simulation using TOUGHREACT. The chemical stimulation method has been applied by numerical modeling to a field geothermal injection well system, to investigate its effectiveness. Parameters from the quartz monzodiorite unit at the Enhanced Geothermal System (EGS) site at Desert Peak (Nevada) were used. Results indicate that the injection of a high pH chelating solution results in dissolution of both calcite and plagioclase minerals, and avoids precipitation of calcite at high temperature conditions. Consequently reservoir porosity and permeability can be enhanced especially near the injection well.

  18. Dispersive liquid-liquid microextraction using diethyldithiocarbamate as a chelating agent and the dried-spot technique for the determination of Fe, Co, Ni, Cu, Zn, Se and Pb by energy-dispersive X-ray fluorescence spectrometry

    NASA Astrophysics Data System (ADS)

    Kocot, Karina; Zawisza, Beata; Sitko, Rafal

    2012-07-01

    Dispersive liquid-liquid microextraction (DLLME) using sodium diethyldithiocarbamate (DDTC) as a chelating agent was investigated for the simultaneous determination of iron, cobalt, nickel, copper, zinc, selenium and lead ions in water samples. The procedure was performed using 5 mL of the sample, 100 μL of a 0.5% solution of DDTC, 30 μL of carbon tetrachloride (extraction phase) and 500 μL of methanol (disperser solvent). The experiments showed that Fe, Co, Ni, Cu, Zn and Pb can be simultaneously extracted at a pH of 5 and that Se can be extracted at a pH of 2-3. The results were compared with those obtained using ammonium pyrrolidine dithiocarbamate as a chelating agent. For all analytes, a linear range was observed up to 0.4 μg mL- 1. If Fe and Zn are present in concentrations 10 times higher than those of the other analytes, then the linearity is observed up to 0.2 μg mL- 1. In the present study, the organic phase that contained preconcentrated elements was deposited onto a Millipore filter and measured using energy-dispersive X-ray fluorescence spectrometry. The obtained detection limits were 2.9, 1.5, 2.0, 2.3, 2.5, 2.0 and 3.9 ng mL- 1 for Fe, Co, Ni, Cu, Zn, Se and Pb, respectively. This combination of DLLME and the dried-spot technique is promising for multielement analyses using other spectroscopy techniques, such as laser ablation-inductively coupled plasma-mass spectrometry, laser-induced breakdown spectroscopy or total-reflection X-ray fluorescence spectrometry.

  19. New class of anti-microbial agents: synthesis, characterization, and anti-microbial activities of metal chelated polyurea.

    PubMed

    Ahamad, Tansir; Kumar, Vikrant; Nishat, Nahid

    2009-02-01

    A new class of metal chelated polyurea have been synthesized by the reaction of toluene 2,4-diisocyanate (TDI) with chelated Schiff base diamines. The synthesized polyurea have been characterized by analytical, spectral, and thermal analysis. The results of TGA ascribed that [Cu(II)-PoU(A)] show better heat resistant properties than other metals chelated polyurea. The antibacterial activities of all the synthesized polymers were determined using the shaking flask method, where 30 mg/mL concentrations of each compound were tested against 10(5) CFU/mL solutions of S. aureus, E. coli, B. subtillis, S. typhi. The number of viable bacteria was calculated by using the spread plate method on agar plates and the number of viable bacteria was counted after 24 h of incubation period at 37 degrees C. All the polymers showed good antibacterial activity. The Cu(II) chelated polyurea show higher zone of inhibition then other due to higher stability constant and may be used in biomedical applications.

  20. A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1(G93A) ALS Mice.

    PubMed

    Golko-Perez, Sagit; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H; Weinreb, Orly

    2017-02-01

    The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1(G93A) transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1(G93A) mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1(G93A) mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1(G93A) mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.

  1. Mercury exposure: evaluation and intervention the inappropriate use of chelating agents in the diagnosis and treatment of putative mercury poisoning.

    PubMed

    Risher, John F; Amler, Sherlita N

    2005-08-01

    Public awareness of the potential for mercury to cause health problems has increased dramatically in the last 15 years. It is now widely recognized that significant exposure to all forms of mercury (elemental/metallic and both inorganic and organic compounds) can result in a variety of adverse health effects, including neurological, renal, respiratory, immune, dermatologic, reproductive, and developmental sequellae. And while the various media have made the general population cognizant of the need to avoid unnecessary exposure to this naturally occurring element, there has also evolved a growing tendency to attribute unexplainable neurologic, as well as other, signs and symptoms to mercury, whether or not significant exposure to mercury has actually occurred. For the physician, making a diagnosis of mercury intoxication can be difficult, because many of the clinical signs and symptoms of mercury exposure can also be attributed to any number of causes, including undiagnosed neurological diseases, pharmacotherapy, vitamin or mineral deficiencies, and psychological stress. The physician must be able to recognize the clinical manifestations of mercury intoxication, and understand the importance of biological markers in making a definitive diagnosis of mercury poisoning. In a desire to treat the patient complaining of symptoms similar to some that can be caused by mercury, a growing number of physicians, particularly those in alternative medicine fields, result to chelation to "rid" the body of the mercury, believed to be the cause of the ailments. And although the use of chelation is increasing, controlled studies showing that this procedure actually improves outcome are lacking. If chelation therapy is considered to be indicated, the attending physician should communicate the risks of chelation to the patient before beginning treatment with metal-chelating drugs.

  2. 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

    PubMed Central

    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

  3. N-Acetyl-Cysteine as Effective and Safe Chelating Agent in Metal-on-Metal Hip-Implanted Patients: Two Cases

    PubMed Central

    Lonati, Davide; Ragghianti, Benedetta; Ronchi, Anna; Vecchio, Sarah; Locatelli, Carlo Alessandro

    2016-01-01

    Systemic toxicity associated with cobalt (Co) and chromium (Cr) containing metal hip alloy may result in neuropathy, cardiomyopathy, and hypothyroidism. However clinical management concerning chelating therapy is still debated in literature. Here are described two metal-on-metal hip-implanted patients in which N-acetyl-cysteine decreased elevated blood metal levels. A 67-year-old male who underwent Co/Cr hip implant in September 2009 referred to our Poison Control Centre for persisting elevated Co/Cr blood levels (from March 2012 to November 2014). After receiving oral high-dose N-acetyl-cysteine, Co/Cr blood concentrations dropped by 86% and 87% of the prechelation levels, respectively, and persisted at these latter concentrations during the following 6 months of follow-up. An 81-year-old female who underwent Co/Cr hip implant in January 2007 referred to our Centre for detection of high Co and Cr blood levels in June 2012. No hip revision was indicated. After a therapy with oral high-dose N-acetyl-cysteine Co/Cr blood concentrations decreased of 45% and 24% of the prechelation levels. Chelating agents reported in hip-implanted patients (EDTA, DMPS, and BAL) are described in few cases. N-acetyl-cysteine may provide chelating sites for metals and in our cases reduced Co and Cr blood levels and resulted well tolerable. PMID:27148463

  4. For Better or Worse, Iron Overload by Superparamagnetic Iron Oxide Nanoparticles as a MRI Contrast Agent for Chronic Liver Diseases.

    PubMed

    Zhou, Qibing; Wei, Yushuang

    2017-01-17

    Superparamagnetic iron oxide nanoparticles (SPIONs) have recently been used as an effective magnetic resonance imaging (MRI) contrast agent for the noninvasive diagnosis of chronic liver diseases including nonalcohol fatty liver diseases, nonalcohol steatohepatitis, and cirrhosis as well as liver tumors. However, the potential risk of the iron overload by SPIONs has been highly underestimated in chronic liver diseases. While most of SPIONs have been shown safe in the healthy group, significant toxicity potential by the iron overload has been revealed through immunotoxicity, lipid peroxidation, and fatty acid and cholesterol metabolism in cirrhosis as a high risk factor. As a result, the systems toxicology assessments of SPIONs are crucial in both healthy ones and chronic liver disease models to determine the margin of safety. In addition, the challenge of the iron overload by SPIONs requires better designed SPIONs as MRI contrast agents for chronic liver diseases such as the biodegradable nanocluster assembly with urine clearance.

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

    PubMed

    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.

  6. Iron (FeII) Chelation, Ferric Reducing Antioxidant Power, and Immune Modulating Potential of Arisaema jacquemontii (Himalayan Cobra Lily)

    PubMed Central

    Sudan, Rasleen; Bhagat, Madhulika; Singh, Jasvinder; Koul, Anupurna

    2014-01-01

    This study explored the antioxidant and immunomodulatory potential of ethnomedicinally valuable species, namely, Arisaema jacquemontii of north-western Himalayan region. The tubers, leaves, and fruits of this plant were subjected to extraction using different solvents. In vitro antioxidant studies were performed in terms of chelation power on ferrous ions and FRAP assay. The crude methanol extract of leaves was found to harbour better chelating capacity (58% at 100 μg/mL) and reducing power (FRAP value 1085.4 ± 0.11 μMFe3+/g dry wt.) than all the other extracts. The crude methanol extract was thus further partitioned with solvents to yield five fractions. Antioxidant study of fractions suggested that the methanol fraction possessed significant chelation capacity (49.7% at 100 μg/mL) and reducing power with FRAP value of 1435.4 μM/g dry wt. The fractions were also studied for immune modulating potential where it was observed that hexane fraction had significant suppressive effect on mitogen induced T-cell and B-cell proliferation and remarkable stimulating effect on humoral response by 141% and on DTH response by 168% in immune suppressed mice as compared to the controls. Therefore, it can be concluded that A. jacquemontii leaves hold considerable antioxidant and immunomodulating potential and they can be explored further for the identification of their chemical composition for a better understanding of their biological activities. PMID:24895548

  7. A simple fluorescent probe for the determination of dissolved oxygen based on the catalytic activation of oxygen by iron(II) chelates.

    PubMed

    Luo, Wei; Abbas, M E; Zhu, Lihua; Zhou, Wenyi; Li, Kejing; Tang, Heqing; Liu, Shushen; Li, Weiying

    2009-04-27

    This work aims at establishing a simple fluorescent probe for the determination of dissolved oxygen. It is found that iron(II) ions activate oxygen to produce reactive species being capable of oxidizing non-fluorescent coumarin to fluorescent 7-hydroxycoumarin. However, this process is not effective because the yield of the reactive species is very low in the presence of simple iron(II) salts alone. The addition of organic ligands such as oxalate results in the formation of complexes between iron(II) ions, which leads to considerable increase in the yield of reactive species (such as hydroxyl radicals) and then increase in the fluorescence intensity of 7-hydroxycoumarin to a significant level. It has been observed that in the mixture solution of iron(II) ions, ligand, coumarin, and dissolved oxygen, there is an excellent linear response between the fluorescence and dissolved oxygen. Therefore, a new spectrofluorimetric method has been proposed for the determination of dissolved oxygen by using catalytic activation of O(2) by iron(II) chelates. Under optimized conditions, a linear correlation (r=0.995) has been observed between the fluorescence intensity of 7-hydroxycoumarin at 456 nm and the concentration of dissolved oxygen over the range of 0.96-9.22 mg L(-1). The limit of detection for dissolved oxygen at a signal-to-noise ratio of 3 has been estimated to be 0.35 mg L(-1). The proposed method has been applied to determine the concentration of dissolved oxygen in practical water samples with results as satisfactory as that obtained by the standard iodometric method.

  8. Use of HPLC for the detection of iron chelators in cultures of bacteria, fungi, and algae. [E. coli; Bacillus megaterium; Ustilago sphaerogena; Anabaena flos-aqua

    SciTech Connect

    Boyer, G.L.; Speirs, R.J.; Morse, P.D. )

    1990-06-01

    Iron is essential for the growth of living cells. To meet biochemical needs, microorganisms, including algae, produce high affinity chelators termed siderophores. These compounds solubilize Fe and increase its bioavailability. We have developed a new method to study siderophore formation in cultured and natural environments. Based on the fact siderophores tightly bind 55-Fe, the radioactive complexes can be separated by HPLC using an inert PRP-1 column and detected by scintillation counting. This method cleanly resolves several known siderophores, including ferrichrome A, ferrichrome, desferal, and rhodotorulic acid. The optimization of the method and its use for analysis of siderophore formation in bacteria (E. coli, and Bacillus megaterium), fungi (Ustilago sphaerogena), and cyanobacteria (Anabaena flos-aqua UTEX 1444 and Anabaena sp. ATCC 27898) will be presented.

  9. Discovery of an extended bundle sheath in Ricinus communis L. and its role as a temporal storage compartment for the iron chelator nicotianamine.

    PubMed

    Rutten, T; Krüger, C; Melzer, M; Stephan, U W; Hell, R

    2003-07-01

    The extended bundle sheath (EBS) is a specialized layer of cells that enhances the lateral transport of photoassimilates within the leaf. This little-known tissue is often considered to be legume-specific. We identified an EBS in cotyledons and leaves of the non-legume Ricinus communis L. By means of cytological and immunological studies and using the localization of the iron-chelator nicotianamine as an established indicator for mass transport, we confirmed its role as a transport tissue and a temporal sink. Observations on cotyledons of Ricinus seedlings further proved that the EBS carries out these tasks from a very early stage of development onwards. This is the first time that information has been obtained on the physiological role of an EBS in a non-legume. Our results support the idea of its widespread occurrence among higher plants.

  10. Hydroxypyridinonate complex stability of group (IV) metals and tetravalent f-block elements: the key to the next generation of chelating agents for radiopharmaceuticals.

    PubMed

    Sturzbecher-Hoehne, Manuel; Choi, Taylor A; Abergel, Rebecca J

    2015-04-06

    The solution thermodynamics of the water-soluble complexes formed between 3,4,3-LI(1,2-HOPO) and Zr(IV) or Pu(IV) were investigated to establish the metal coordination properties of this octadentate chelating agent. Stability constants log β110 = 43.1 ± 0.6 and 43.5 ± 0.7 were determined for [Zr(IV)(3,4,3-LI(1,2-HOPO))] and [Pu(IV)(3,4,3-LI(1,2-HOPO))], respectively, by spectrophotometric competition titrations against Ce(IV). Such high thermodynamic stabilities not only confirm the unparalleled Pu(IV) affinity of 3,4,3-LI(1,2-HOPO) as a decorporation agent but also corroborate the great potential of hydroxypyridinonate ligands as new (89)Zr-chelating platforms for immuno-PET applications. These experimental values are in excellent agreement with previous estimates and are discussed with respect to ionic radius and electronic configuration, in comparison with those of Ce(IV) and Th(IV). Furthermore, a liquid chromatography assay combined with mass spectrometric detection was developed to probe the separation of the neutral [M(IV)(3,4,3-LI(1,2-HOPO))] complex species (M = Zr, Ce, Th, and Pu), providing additional insight into the coordination differences between group IV and tetravalent f-block metals and on the role of d and f orbitals in bonding interactions.

  11. Influence of Glacial Acetic Acid and Nitric Acid as a Chelating Agent in Sol-gel Process to the Nanostructured Titanium Dioxide Thin Films

    NASA Astrophysics Data System (ADS)

    Ahmad, M. K.; Rusop, M.

    2009-06-01

    The comparison between different chelating agents in sol-gel process for deposition of nanostructured Titanium Dioxide (TiO2) thin film has been studied. Glacial Acetic Acid (GA) and Nitric Acid (NA) were used in 0.2 M of concentration. The effects to the structural, electrical and optical properties have been studied. The effects of these properties were characterized using X-Ray Diffractometer (XRD), 2-point probe I-V measurement and UV-Vis-NIR Spectrophotometer. For electrical properties, it showed that nanostructured TiO2 thin film that using GA (TF-GA) as chelating agent gives better low sheet resistance compare to nanostructured TiO2 thin film using NA (TF-NA). From XRD results, it indicates that no significantly different between both TiO2 thin film. Both of thin films have crystalline anatase phase at 2θ degree 25.8° which corresponded to (101) orientation. For optical properties, sol-gel using GA has slightly higher in transmittance spectra properties but both of films fully absorbed UV light at 300 nm of wavelength. As for optical band gap, both sol-gels using GA and NA has similar optical band gap which is 3.27 eV.

  12. Iron-control additives improve acidizing

    SciTech Connect

    Walker, M.; Dill, W. ); Besler, M. )

    1989-07-24

    Iron sulfide and sulfur precipitation in sour wells can be controlled with iron-sequestering agents and sulfide modifiers. Oil production has been routinely increased in sour wells where precipitation of iron sulfide and elemental sulfur has been brought under control. Production increases have been especially noteworthy on wells that had a history of rapid production decline after acid stimulation. Twenty-fold production increases have been recorded. Key to the production increase has been to increase permeability with: Iron chelating agents that control precipitation of iron sulfide. A sulfide modifier that reduces precipitation of solids in the presence of excessive amounts of hydrogen sulfide and prevents precipitation of elemental sulfur.

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

    PubMed

    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.

  14. Metal Chelating Crosslinkers Form Nanogels with High Chelation Stability.

    PubMed

    Lux, Jacques; Chan, Minnie; Elst, Luce Vander; Schopf, Eric; Mahmoud, Enas; Laurent, Sophie; Almutairi, Adah

    2013-12-14

    We present a series of hydrogel nanoparticles (nanogels) incorporating either acyclic or cyclic metal chelates as crosslinkers. These crosslinkers are used to formulate polyacrylamide-based nanogels (diameter 50 to 85 nm) yielding contrast agents with enhanced relaxivities (up to 6-fold greater than Dotarem®), because this nanogel structure slows the chelator's tumbling frequency and allows fast water exchange. Importantly, these nanogels also stabilize Gd(3+) within the chelator thermodynamically and kinetically against metal displacement through transmetallation, which should reduce toxicity associated with release of free Gd(3+). This chelation stability suggests that the chelate crosslinker strategy may prove useful for other applications of metal-chelating nanoparticles in medicine, including other imaging modalities and radiotherapy.

  15. Metal Chelating Crosslinkers Form Nanogels with High Chelation Stability

    PubMed Central

    Elst, Luce Vander; Schopf, Eric; Mahmoud, Enas; Laurent, Sophie; Almutairi, Adah

    2013-01-01

    We present a series of hydrogel nanoparticles (nanogels) incorporating either acyclic or cyclic metal chelates as crosslinkers. These crosslinkers are used to formulate polyacrylamide-based nanogels (diameter 50 to 85 nm) yielding contrast agents with enhanced relaxivities (up to 6-fold greater than Dotarem®), because this nanogel structure slows the chelator's tumbling frequency and allows fast water exchange. Importantly, these nanogels also stabilize Gd3+ within the chelator thermodynamically and kinetically against metal displacement through transmetallation, which should reduce toxicity associated with release of free Gd3+. This chelation stability suggests that the chelate crosslinker strategy may prove useful for other applications of metal-chelating nanoparticles in medicine, including other imaging modalities and radiotherapy. PMID:24505553

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

    PubMed

    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.

  17. Iron chelation and redox chemistry of anthranilic acid and 3-hydroxyanthranilic acid: A comparison of two structurally related kynurenine pathway metabolites to obtain improved insights into their potential role in neurological disease development

    PubMed Central

    Chobot, Vladimir; Hadacek, Franz; Weckwerth, Wolfram; Kubicova, Lenka

    2015-01-01

    Anthranilic acid (ANA) and 3-hydroxyanthranilic acid (3-HANA) are kynurenine pathway intermediates of the tryptophan metabolism. A hitherto unemployed method combination, differential pulse voltammetry, mass spectrometry (nano-ESI–MS), deoxyribose degradation and iron(II) autoxidation assays has been employed for studying of their redox chemistry and their interactions with iron(II) and iron(III) ions. Both acids inhibited the Fenton reaction by iron chelation and ROS scavenging in the deoxyribose degradation assay. In the iron(II) autoxidation assay, anthranilic acid showed antioxidant effects, whereas 3-hydroxyanthranilic acid exhibited apparent pro-oxidant activity. The differential pulse voltammograms of free metabolites and their iron(II) coordination complexes reflected these properties. Nano-ESI–MS confirmed ANA and 3-HANA as efficient iron(II) chelators, both of which form coordination complexes of ligand:iron(II) ratio 1:1, 2:1, and 3:1. In addition, nano-ESI–MS analyses of the oxidation effects by hydroxyl radical attack identified 3-HANA as strikingly more susceptible than ANA. 3-HANA susceptibility to oxidation may explain its decreased concentrations in the reaction mixture. The presented observations can add to explaining why 3-HANA levels decrease in patients with some neurological and other diseases which can often associated with elevated concentrations of ROS. PMID:25892823

  18. The effect of iron on the biodistribution of bone scanning agents in humans

    SciTech Connect

    Choy, D.; Murray, I.P.; Hoschl, R.

    1981-07-01

    Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of 99mTc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling.

  19. 1: Mass asymmetric fission barriers for {sup 98}Mo; 2: Synthesis and characterization of actinide-specific chelating agents

    SciTech Connect

    Veeck, A.C. ||

    1996-08-01

    Excitation functions have been measured for complex fragment emission from the compound nucleus {sup 98}Mo, produced by the reaction of {sup 86}Kr with {sup 12}C. Mass asymmetric fission barriers have been obtained by fitting the excitation functions with a transition state formalism. The extracted barriers are {approximately} 5.7 MeV higher, on average, than the calculations of the Rotating Finite Range Model (RFRM). These data clearly show an isospin dependence of the conditional barriers when compared with the extracted barriers from {sup 90}Mo and {sup 94}Mo. Eleven different liquid/liquid extractants were synthesized based upon the chelating moieties 3,2-HOPO and 3,4-HOPO; additionally, two liquid/liquid extractants based upon the 1,2-HOPO chelating moiety were obtained for extraction studies. The Pu(IV) extractions, quite surprisingly, yielded results that were very different from the Fe(III) extractions. The first trend remained the same: the 1,2-HOPOs were the best extractants, followed closely by the 3,2-HOPOs, followed by the 3,4-HOPOs; but in these Pu(IV) extractions the 3,4-HOPOs performed much better than in the Fe(III) extractions. 129 refs.

  20. Controlled hydrothermal growth of ZnO nanostructures by sequestering the Zn metal ions with the chelating agent EDTA

    NASA Astrophysics Data System (ADS)

    Ram, S. D. Gopal; Ravi, G.; Manikandan, MR.; Mahalingam, T.; Anbu Kulandainathan, M.

    2011-10-01

    In the present work, a controlled growth of ZnO nanostructures by manipulating Zn metal ion concentration by the chelating action of ethylene diaminetetra acetic acid in hydrothermal method is studied. EDTA produces metal-chelate complex by the formation of bidentate ligand with Zn 2+ in the solution and diminishes the reactivity of Zn metal cations. Concentration of EDTA in the mother solution was varied in different ranges like 3, 5 and 10 mM while retaining the zinc metal salt and the NaOH concentration the same. Three different morphologies of wurtzite structured ZnO nanostructures such as nanorods-bunch, separate/discrete uniformly sized hexagonal nanorods and tapered flower petals like shapes are achieved by 3, 5 and 10 mM strengths of EDTA, respectively. The medium concentration 5 mM of EDTA is found to have moderate control over producing ZnO nanostructures of uniform diameter and a high aspect (length to diameter) ratio. An array of vertically aligned free standing ZnO nanorods with uniform spacing is successfully achieved by the addition of 5 mM of EDTA in the mother solution and the same is studied for its fluorescence property at an excitation of 325 nm and it has exhibited a characteristic UV emission of ZnO around 383 nm.

  1. New biodegradable organic-soluble chelating agents for simultaneous removal of heavy metals and organic pollutants from contaminated media.

    PubMed

    Ullmann, Amos; Brauner, Neima; Vazana, Shlomi; Katz, Zhanna; Goikhman, Roman; Seemann, Boaz; Marom, Hanit; Gozin, Michael

    2013-09-15

    Advanced biodegradable and non-toxic organic chelators, which are soluble in organic media, were synthesized on the basis of the S,S-ethylenediamine-disuccinate (S,S-EDDS) ligand. The modifications suggested in this work include attachment of a lipophilic hydrocarbon chain ("tail") to one or both nitrogen atoms of the S,S-EDDS. The new ligands were designed and evaluated for application in the Sediments Remediation Phase Transition Extraction (SR-PTE) process. This novel process is being developed for the simultaneous removal of both heavy metals and organic pollutants from contaminated soils, sediments or sludge. The new chelators were designed to bind various target metal ions, to promote extraction of these ions into organic solvents. Several variations of attached tails were synthesized and tested. The results for one of them, N,N'-bis-dodecyl-S,S-EDDS (C24-EDDS), showed that the metal-ligand complexes are concentrated in the organic-rich phase in the Phase Transition Extraction process (more than 80%). Preliminary applications of the SR-PTE process with the C24-EDDS ligand were conducted also on actually contaminated sludge (field samples). The extraction of five toxic metals, namely, Cd, Cu, Ni, Pb and Zn was examined. In general, the extraction performance of the new ligand was not less than that of S,S-EDDS when a sufficient ligand-to-extracted ion ratio (about 4:1 was applied.

  2. Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials.

    PubMed

    Maggio, Aurelio; Filosa, Aldo; Vitrano, Angela; Aloj, Giuseppina; Kattamis, Antonis; Ceci, Adriana; Fucharoen, Suthat; Cianciulli, Paolo; Grady, Robert W; Prossomariti, Luciano; Porter, John B; Iacono, Angela; Cappellini, Maria Domenica; Bonifazi, Fedele; Cassarà, Filippo; Harmatz, Paul; Wood, John; Gluud, Christian

    2011-10-15

    The effectiveness of deferoxamine (DFO), deferiprone (DFP), or deferasirox (DFX) in thalassemia major was assessed. Outcomes were reported as means±SD, mean differences with 95% CI, or standardized mean differences. Statistical heterogeneity was tested using χ2 (Q) and I2. Sources of bias and Grading of Recommendations Assessment, Development and Evaluation system (GRADE) were considered. Overall, 1520 patients were included. Only 7.4% of trials were free of bias. Overall measurements suggest low trial quality (GRADE). The meta-analysis suggests lower final liver iron concentrations during associated versus monotherapy treatment (p<0.0001), increases in serum ferritin levels during DFX 5, 10, and 20 mg/kg versus DFO-treated groups (p<0.00001, p<0.00001, and p=0.002, respectively), but no statistically significant difference during DFX 30 mg/kg versus DFO (p=0.70), no statistically significant variations in heart T2* signal during associated or sequential versus mono-therapy treatment (p=0.46 and p=0.14, respectively), increases in urinary iron excretion during associated or sequential versus monotherapy treatment (p=0.008 and p=0.02, respectively), and improved ejection fraction during associated or sequential versus monotherapy treatment (p=0.01 and p<0.00001, respectively). These findings do not support any specific chelation treatment. The literature shows risks of bias, and additional larger and longer trials are needed.

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

    PubMed

    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.

  4. Removal of pyrite and trace elements from waste coal by dissolved- CO{sub 2} flotation and chelating agents. Technical report, September 1, 1993--November 30, 1993

    SciTech Connect

    Shiao, S.Y.

    1993-12-31

    In dissolved-CO{sub 2} flotation, ultrafine bubbles are generated by CO{sub 2} dissolved in water. The ultrafine bubbles have the potential to improve the separation efficiency in fine coal cleaning. Chemicals will be used prior to or during dissolved-CO{sub 2} flotation to improve the separation efficiency of pyrite and other minerals including trace metals from coal. Chelating agents will be applied to clean coal to further reduce the trace metals from coal. During this period, the project planning has begun. A 3in.-diameter packed column has been ordered. This column will be modified for use in dissolved-CO{sub 2} flotation. Clean and waste coal samples of Illinois No. 6 coal have been scheduled to be picked up from Ohio Coal Testing and Development (OCTAD) facility.

  5. Removal of pyrite and trace elements from waste coal by dissolved-CO{sub 2} flotation and chelating agents. [Quarterly] technical report, December 1, 1993--February 28, 1994

    SciTech Connect

    Shiao, S.Y.

    1994-08-01

    In dissolved-CO{sub 2} flotation, ultrafine -bubbles are generated by CO{sub 2} dissolved in water. The ultrafine bubbles have the potential to improve the separation efficiency in fine coal cleaning. Chemicals will be used prior to or during dissolved-CO{sub 2} flotation to improve the separation efficiency-CO{sub 2} of pyrite and other minerals including trace metals from coal. Chelating agent will be applied to clean coal to further reduce the trace metals from coal. During this period, a 3 in. diameter packed column has been purchased and installed. This column was then modified for use in dissolved-CO{sub 2} flotation. Coal samples of Illinois No. 6 coal are being prepared for flotation. Preliminary flotation tests were performed on Illinois No. 6 waste coal.

  6. Effect of Surface Modification by Chelating Agents on Fischer–Tropsch Performance of Co/SiO2 Catalysts

    SciTech Connect

    Bambal, Ashish S.; Kugler, Edwin L.; Gardner, Todd H.; Dadyburjor, Dady B.

    2013-11-27

    The silica support of a Co-based catalyst for Fischer–Tropsch (FT) synthesis was modified by the chelating agents (CAs) nitrilotriacetic acid (NTA) and ethylenediaminetetraacetic acid (EDTA). After the modification, characterization of the fresh and spent catalysts shows reduced crystallite sizes, a better-dispersed Co3O4 phase on the calcined samples, and increased metal dispersions for the reduced samples. The CA-modified catalysts display higher CO conversions, product yields, reaction rates, and rate constants. The improved FT performance of CA-modified catalysts is attributed to the formation of stable complexes with Co. Finally, the superior performance of the EDTA-modified catalyst in comparison to the NTA-modified catalyst is due to the higher affinity of the former for complex formation with Co ions.

  7. Microstructure, Optical and Photocatalytic Properties of TiO₂ Thin Films Prepared by Chelating-Agent Assisted Sol-Gel Method.

    PubMed

    Matĕjová, Lenka; Cieslarová, Monika; Matĕj, Zdenĕk; Danis, Stanislav; Peikertová, Pavlína; Sihor, Marcel; Lang, Jaroslav; Matĕjka, Vlastimil

    2016-01-01

    Single and multilayer TiO₂ thin films coated on two types of soda-lime glass substrates (microscope slides and cylinders) were prepared by a chelating agent-assisted sol-gel method, using ethyl acetoacetate as a chelating agent, dip-coating and calcination at 500 °C for 2 h in air. Phase composition, microstructural, morphological and optical properties of thin films were comprehensively investigated by using XRF, advanced XRD analysis, Raman and UV-vis spectroscopy and AFM. It was found out that the thickness of thin films increases linearly with increasing number of deposited layers, indicating a good adhesion of the titania solution to a glass substrate as well as to a previously calcined layer. 1 layer film crystallized to anatase-TiO₂(B) mixture with minor/negligible amount of nanosized brookite, 2-4 layers films crystallized to anatase-brookite-TiO₂(B) mixture. In contrast to other multilayers films, 4 layers film was highly inhomogeneous. The different phase composition of thin films was clarified based on the crystallization via titanate/s and metastable monoclinic TiO₂(B) as a consequence of several phenomena; the diffusion of Na⁺ ions from a soda-lime glass substrate, acidic conditions and repeated thermal treatment. The multilayer films were in average highly transparent (80-95%) in the visible light region with the sharp absorption edge in the UV light region. Additionally, the photocatalytic properties of selected multilayer films were compared in AO7 photodegradation. Photocatalytic experiments showed that thicker 4 layers film of tricrystalline anatase-brookite-TiO₂(B) phase mixture was similarly active as thinner 3 layers film of similar phase composition, which may be a consequence of the inhomogeneity of the thicker film.

  8. Removal of pyrite and trace elements from waste coal by dissolved-CO{sub 2} flotation and chelating agents. Final technical report, September 1, 1993--August 31, 1994

    SciTech Connect

    Shiao, S.Y.; Ho, K.

    1994-12-31

    The overall objective of this project was to use ultrafine bubbles generated by dissolved C0{sub 2} to recover useable fuel, and reject pyrite and other minerals from a waste coal in flotation. In addition, a chelating agent was used to remove trace metals from the froth products. Illinois No. 6 waste coal obtained from a refuse thickener of a coal cleaning circuit was used as the feed in flotation. The as-received waste coal had a top size of 2400 microns. The waste coal was ground to {minus}75 microns ({minus}200 mesh) and {minus}44 microns ({minus}325 mesh). The as-received and the ground waste coal samples were subjected to flotation. Dissolved-CO{sub 2} flotation tests were performed mainly in a 3-inch diameter by 8 feet high packed column under various test conditions. Some tests were also performed in a 2-inch diameter microbubble column for comparison. The flotation performance of the waste coal in the microbubble column was higher than that for the packed column. The packing in the packed column hindered the coal flotation. The separation efficiency of the ground coal was less than that for the asreceived coal. Flotation of the waste coal was also performed in the packed column using coarser bubbles generated by dispersed C0{sub 2} and air. The separation efficiency of the ground waste coal of 44 microns top size was higher than that for dissolved-CO{sub 2} flotation. Additives were used to modify the waste coal surfaces. Triton-X 100, a nonionic surfactant and EDTA, a chelating agent, increased the separation efficiency of the waste coal.Most of the trace metals in coal were reduced in different degrees by flotation. Triton X-100 or EDTA enhanced removal of chromium, nickel, and selenium. Applying EDTA to the froth products further removed lead significantly.

  9. Iron removal on feldspar by using Averrhoa bilimbii as bioleaching agent

    NASA Astrophysics Data System (ADS)

    Amin, Muhammad; Aji, Bramantyo B.; Supriyatna, Yayat Iman; Bahfie, Fathan

    2017-01-01

    Investigation of Averrhoa bilimbii as bioleaching agent was carried out. Parameters of leaching duration, acid concentration, and temperature were performed in iron removal process. Feldspar with sized 149 µm was diluted in 30 ml acid solution in order to reduce its iron content. The experimental results showed a good technical feasibility of the process which iron oxide content of feldspar was decreased from 2.24% to 0.29%. The lowest iron concentration remained was obtained after 5 hours of leaching treatment at 60 °C, and concentrated (100 vol%) Averrhoa bilimbii extract as bioleaching agent. SEM characterizations were carried out on the feldspar before and after the leaching treatment. The result shows that there were no significant effect of leaching process on the ore morphology.

  10. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease.

    PubMed

    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.

  11. Chelate-Assisted Heavy Metal Movement Through the Root Zone

    NASA Astrophysics Data System (ADS)

    Kirkham, M.; Madrid, F.; Liphadzi, M. S.

    2001-12-01

    Chelating agents are added to soil as a means to mobilize heavy metals for plant uptake during phytoremediation. Yet almost no studies follow the displacement of heavy metals through the vadose zone following solubilization with chelating agents. The objective of this work was to determine the movement of heavy metals through the soil profile and their absorption by barley (Hordeum vulgare L.) in a soil amended with biosolids and in the presence of a chelating agent (EDTA). Twelve columns 75 cm in height and 17 in diameter were packed with a Haynie very fine sandy loam (coarse-silty, mixed, calcareous, mesic Mollic Udifluvents) and watered with liquid biosolids applied at the surface at a rate of 120 kg N/ha. Three weeks after plants germinated, soil was irrigated with a solution of the disodium salt of EDTA added at a rate of 0.5 g/kg soil. Four treatments were imposed: columns with no plants and no EDTA; columns with no plants plus EDTA; columns with plants and no EDTA; and columns with plants and EDTA. Columns were watered intensively for 35 days until two pore volumes of water had been added, and the leachates were collected daily. With or without plants, columns with EDTA had lower total concentrations of Cu, Zn, Cd, Ni, and Pb in the surface 20 cm than columns without EDTA. Concentrations of the heavy metals in this layer were not afffected by the presence of roots. Iron in leachate was followed as an indicator metal for movement to groundwater. No iron appeared in the leachate without EDTA, either in the columns with plants or without plants. The peak concentration of iron in the leachate occurred three days earlier in the columns without plants and EDTA compared to the columns with plants and EDTA. The results indicated the importance of vegetation on retarding heavy metal leaching to groundwater during chelate-facilitated phytoremediation.

  12. Biomimetic Actinide Chelators: An Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO)

    PubMed Central

    Abergel, Rebecca J.; Durbin, Patricia W.; Kullgren, Birgitta; Ebbe, Shirley N.; Xu, Jide; Chang, Polly Y.; Bunin, Deborah I.; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Rosen, Chris J.; Shuh, David K.; Raymond, Kenneth N.

    2010-01-01

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (> 100 μmol kg−1 day−1) over 28 days under good laboratory practice (GLP) guidelines. Both compounds are on an accelerated development pathway towards clinical use. PMID:20699704

  13. Biomimetic actinide chelators: an update on the preclinical development of the orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO).

    PubMed

    Abergel, Rebecca J; Durbin, Patricia W; Kullgren, Birgitta; Ebbe, Shirley N; Xu, Jide; Chang, Polly Y; Bunin, Deborah I; Blakely, Eleanor A; Bjornstad, Kathleen A; Rosen, Chris J; Shuh, David K; Raymond, Kenneth N

    2010-09-01

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.

  14. Biomimetic Actinide Chelators: An Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO)

    SciTech Connect

    Durbin, Patricia W.; Kullgren, Birgitta; Ebbe, Shirley N.; Xu, Jide; Chang, Polly Y.; Bunin, Deborah I.; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Rosen, Chris J.; Shuh, David K.; Raymond, Kenneth N.

    2011-07-13

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.

  15. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    PubMed Central

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-01-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies. PMID:25727482

  16. The impact of extraction with a chelating agent under acidic conditions on the cell wall polymers of mango peel.

    PubMed

    Jamsazzadeh Kermani, Zahra; Shpigelman, Avi; Kyomugasho, Clare; Van Buggenhout, Sandy; Ramezani, Mohsen; Van Loey, Ann M; Hendrickx, Marc E

    2014-10-15

    The objective of this research was to evaluate whether mango peel is a potential source of functional cell wall polymers. To reach this objective, the native pectin polymers (NPP) extracted as alcohol insoluble residue from mango peel, were characterised in terms of uronic acid content, degree of methoxylation, neutral sugar content, and molar mass and compared to citric acid (pH 2.5, 2h at 80°C) extracted polymers, mimicking industrial pectin extraction conditions. Water-solubilised NPP were highly methoxylated having two populations with a Mw of 904 and 83kDa and a degree of methoxylation of 66%. Citric acid extraction with a yield higher than H2SO4 extraction resulted in a very branched pectin with an extremely high DM (83%) and a high molar mass. Comparing the Fourier Transform Infra-Red spectroscopy of extracted and native WSF showed that citric acid remained partially associated to the extracted pectin due to its chelating properties.

  17. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    DOE PAGES

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; ...

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) ismore » unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.« less

  18. In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)

    SciTech Connect

    Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J.

    2015-02-27

    We report that the hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 minutes, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of co-administered drugs metabolized by these enzymes. Plasma protein binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bi-directional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.

  19. In vitro metabolism and stability of the actinide chelating agent 3,4,3-LI(1,2-HOPO).

    PubMed

    Choi, Taylor A; Furimsky, Anna M; Swezey, Robert; Bunin, Deborah I; Byrge, Patricia; Iyer, Lalitha V; Chang, Polly Y; Abergel, Rebecca J

    2015-05-01

    The hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO) is currently under development for radionuclide chelation therapy. The preclinical characterization of this highly promising ligand comprised the evaluation of its in vitro properties, including microsomal, plasma, and gastrointestinal fluid stability, cytochrome P450 inhibition, plasma protein binding, and intestinal absorption using the Caco-2 cell line. When mixed with active human liver microsomes, no loss of parent compound was observed after 60 min, indicating compound stability in the presence of liver microsomal P450. At the tested concentrations, 3,4,3-LI(1,2-HOPO) did not significantly influence the activities of any of the cytochromal isoforms screened. Thus, 3,4,3-LI(1,2-HOPO) is unlikely to cause drug-drug interactions by inhibiting the metabolic clearance of coadministered drugs metabolized by these enzymes. Plasma protein-binding assays revealed that the compound is protein-bound in dogs and less extensively in rats and humans. In the plasma stability study, the compound was stable after 1 h at 37°C in mouse, rat, dog, and human plasma samples. Finally, a bidirectional permeability assay demonstrated that 3,4,3-LI(1,2-HOPO) is not permeable across the Caco-2 monolayer, highlighting the need to further evaluate the effects of various compounds with known permeability enhancement properties on the permeability of the ligand in future studies.

  20. How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study.

    PubMed

    Conte-Daban, Amandine; Day, Adam; Faller, Peter; Hureau, Christelle

    2016-10-04

    The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-β (Aβ) peptide, i.e. to the modulation of Aβ aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of both ions in Aβ aggregation is still controversial. Conversely the higher toxicity of the redox competent Cu ions (compared to the redox inert Zn ions) in ROS production is acknowledged. Thus the Cu ions can be considered as the main therapeutic target. Because Zn ions are present in higher quantity than Cu ions in the synaptic cleft, they can prevent detoxification of Cu by chelators unless they have an unusually high Cu over Zn selectivity. We describe a proof-of-concept study where the role of Zn on the metal swap reaction between two prototypical ligands and the Cu(Aβ) species has been investigated by several complementary spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher Cu over Zn selectivity relative to the one of Aβ peptide while the second one exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the ligands on Cu-induced ROS production and Aβ aggregation is also reported.

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

    PubMed

    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.

  2. Synthesis of 4-substituted-trans-1,2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and spect and pet imaging

    DOEpatents

    Mease, Ronnie C.; Kolsky, Kathryn L.; Mausner, Leonard F.; Srivastava, Suresh C.

    1997-06-03

    Cyclohexyl chelating agents useful in forming antibody-metal conjugates useful for diagnostic and therapeutic purposes. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2-diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2-diamino cyclohexane-N, N, N', N'-tetra acetic acid.

  3. Synthesis of 4-substituted-trans-1,2-diaminocyclohexyl polyaminocarboxylate metal chelating agents for the preparation of stable radiometal antibody immunoconjugates for therapy and SPECT and PET imaging

    DOEpatents

    Mease, R.C.; Kolsky, K.L.; Mausner, L.F.; Srivastava, S.C.

    1997-06-03

    Cyclohexyl chelating agents useful in forming antibody-metal conjugates which are used for diagnostic and therapeutic purposes are synthesized. New compounds and processes of forming these compounds are disclosed including 4-haloacetamido-trans-1,2-diaminocyclohexyl polyaminocarboxylate and 4-isothiocyanato-trans-1,2-diamino cyclohexane-N,N,N{prime},N{prime}-tetra acetic acid.

  4. Chemistry of bifunctional photoprobes. 3 -- Correlation between the efficiency of CH insertion by photolabile chelating agents and lifetimes of singlet nitrenes by flash photolysis: First example of photochemical attachment of {sup 99m}Tc-complex with human serum albumin

    SciTech Connect

    Pandurangi, R.S.; Lusiak, P.; Kuntz, R.R.; Volkert, W.A.; Rogowski, J.; Platz, M.S.

    1998-11-27

    Systematic functionalization of perfluoroaryl azides with chelating agents capable of complexing transition metals produces a new class of bifunctional photolabile chelating agents (BFPCAs). The strategy is shield the azide functionality from the electronic and steric influence of the electron-rich metal Pd through ester and amide bridges raised CH insertion efficiency to unprecedented levels (>92%) in a model solvent (cyclohexane). In contrast, perfluoroaryl azides attached to chelating agents via hydrazones show no significant CH insertion in cyclohexane upon photolysis. Measurements of the lifetimes of the singlet nitrenes derived from these agents by flash photolysis techniques correlate well with the efficiency of CH insertion by demonstrating longer lifetimes (10--50 times) for singlet nitrenes derived from azidotetrafluorinated esters and amides compared with the related hydrazones, which failed to yield significant CH insertion. A representative BFPCA 12 is chelated to diagnostic radionuclide {sup 99m}Tc and covalently attached to human serum albumin via photochemical activation extending the favorable bimolecular insertion characteristics of BFPCA to tracer level concentrations in buffer conditions. Flash photolysis experiments correlate singlet nitrene lifetimes with the efficiency of intermolecular insertion reactions. This work provides new photo-cross-linking technology, useful in radiodiagnostics and radiotherapy in nuclear medicine.

  5. A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

    NASA Astrophysics Data System (ADS)

    Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

    2009-05-01

    A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

  6. Targeting the metastasis suppressor, NDRG1, using novel iron chelators: regulation of stress fiber-mediated tumor cell migration via modulation of the ROCK1/pMLC2 signaling pathway.

    PubMed

    Sun, Jing; Zhang, Daohai; Zheng, Ying; Zhao, Qian; Zheng, Minhua; Kovacevic, Zaklina; Richardson, Des R

    2013-02-01

    The iron-regulated metastasis suppressor, N-myc downstream-regulated gene 1 (NDRG1), is up-regulated by cellular iron depletion mediated by iron chelators and can inhibit cancer cell migration. However, the mechanism of how NDRG1 achieves this effect remains unclear. In this study, we implemented established and newly constructed NDRG1 overexpression and knockdown models using the DU145, HT29, and HCT116 cancer cell lines to investigate the molecular basis by which NDRG1 exerts its inhibitory effect on cell migration. Using these models, we demonstrated that NDRG1 overexpression inhibits cell migration by preventing actin-filament polymerization, stress fiber assembly and formation. In contrast, NDRG1 knockdown had the opposite effect. Moreover, we identified that NDRG1 inhibited an important regulatory pathway mediated by the Rho-associated, coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated myosin light chain 2 (pMLC2) pathway that modulates stress fiber assembly. The phosphorylation of MLC2 is a key process in inducing stress fiber contraction, and this was shown to be markedly decreased or increased by NDRG1 overexpression or knockdown, respectively. The mechanism involved in the inhibition of MLC2 phosphorylation by NDRG1 was mediated by a significant (P < 0.001) decrease in ROCK1 expression that is a key kinase involved in MLC2 phosphorylation. Considering that NDRG1 is up-regulated after cellular iron depletion, novel thiosemicarbazone iron chelators (e.g., di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone) were demonstrated to inhibit ROCK1/pMLC2-modulated actin-filament polymerization, stress fiber assembly, and formation via a mechanism involving NDRG1. These results highlight the role of the ROCK1/pMLC2 pathway in the NDRG1-mediated antimetastatic signaling network and the therapeutic potential of iron chelators at inhibiting metastasis.

  7. Restoration of nigrostriatal dopamine neurons in post-MPTP treatment by the novel multifunctional brain-permeable iron chelator-monoamine oxidase inhibitor drug, M30.

    PubMed

    Gal, Shunit; Zheng, Hailin; Fridkin, Mati; Youdim, Moussa B H

    2010-01-01

    The anti-Parkinson iron chelator-monoamine oxidase inhibitor M30 [5-(N-methyl-N-propargyaminomethyl)-8-hydroxyquinoline] was shown to possess neuroprotective activities in vitro and in vivo, against several insults applicable to several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and ALS. In the present study we sought to examine the effect of M30 on a pre-existing lesion induced by the parkinsonism-inducing toxin, MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). In this neurorescue paradigm, M30 orally administered to mice for 14 days (2.5 mg/kg/day) following MPTP was shown to significantly elevate striatal dopamine levels, reduce its metabolism, and elevate tyrosine-hydroxylase protein levels (from 25.86 +/- 5.10 to 68.35 +/- 10.67% of control) and activity (from 7.52 +/- 0.98 to 16.33 +/- 2.92 pmol/mg protein/min). Importantly, M30 elevated MPTP-reduced dopaminergic (from 62.8 +/- 4.1 to 84.2 +/- 5.9% of control) and transferrin receptor (from 31.3 +/- 2.6 to 80.4 +/- 7.6% of control) cell count in the SNpc. Finally, M30 was shown to decrease mitosis, thus providing additional protection. These findings suggest that brain-permeable M30 may clearly be of clinical importance for the treatment of PD.

  8. Iron Oxide Decorated MoS2 Nanosheets with Double PEGylation for Chelator-Free Radiolabeling and Multimodal Imaging Guided Photothermal Therapy

    PubMed Central

    Liu, Teng; Shi, Sixiang; Liang, Chao; Shen, Sida; Cheng, Liang; Wang, Chao; Song, Xuejiao; Goel, Shreya; Barnhart, Todd E.; Cai, Weibo; Liu, Zhuang

    2015-01-01

    Theranostics for in vivo cancer diagnosis and treatment generally requires well-designed nanoscale platforms with multiple integrated functionalities. In this study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur chemistry, forming MoS2-IO nanocomposites, which are then modified with two types of polyethylene glycol (PEG) to acquire enhanced stability in physiological environments. Interestingly, 64Cu, a commonly used positron-emitting radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of chelating molecules, to enable in vivo positron emission tomography (PET) imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and magnetic resonance (MR) imaging, respectively. Under the guidance by such triple-modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon intravenous injection, in vivo photothermal therapy is finally conducted, achieving effective tumor ablation in an animal tumor model. Our study highlights the promise of constructing multifunctional theranostic nanocomposites based on 2D transitional metal dichalcogenides for multimodal imaging-guided cancer therapy. PMID:25562533

  9. Suppression by iron chelator phenanthroline of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

    PubMed

    Tatsuta, Masaharu; Iishi, Hiroyasu; Baba, Miyako; Mikuni, Tomiko; Narahara, Hiroyuki; Uedo, Noriya; Yano, Hiroyuki

    2003-02-28

    The effect of prolonged administration of iron chelator phenanthroline on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and intraperitoneal injections of phenanthroline at doses of 15 or 30 mg/kg body weight every other day. At week 52, feeding of sodium chloride significantly increased the incidence of gastric cancers, as compared with the control group. Prolonged injections of phenanthroline at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral supplementation with sodium chloride. Phenanthroline at both doses significantly decreased the labeling index of gastric cancers, which was enhanced by sodium chloride, and significantly increased the apoptotic index of gastric cancers, which was lowered by sodium chloride. In vitro examination using electron spin resonance revealed that sodium chloride promotes the production of hydroxyl radical during Fe(2+) oxidation by Fenton's reaction. These findings suggest that enhancement by sodium chloride of gastric carcinogenesis may be mediated by hydroxyl radicals.

  10. Lauriston S. Taylor Lecture: the quest for therapeutic actinide chelators.

    PubMed

    Durbin, Patricia W

    2008-11-01

    All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage.

  11. Gd(iii) and Mn(ii) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins.

    PubMed

    Kaushik, Monu; Bahrenberg, Thorsten; Can, Thach V; Caporini, Marc A; Silvers, Robert; Heiliger, Jörg; Smith, Albert A; Schwalbe, Harald; Griffin, Robert G; Corzilius, Björn

    2016-10-21

    We investigate complexes of two paramagnetic metal ions Gd(3+) and Mn(2+) to serve as polarizing agents for solid-state dynamic nuclear polarization (DNP) of (1)H, (13)C, and (15)N at magnetic fields of 5, 9.4, and 14.1 T. Both ions are half-integer high-spin systems with a zero-field splitting and therefore exhibit a broadening of the mS = -1/2 ↔ +1/2 central transition which scales inversely with the external field strength. We investigate experimentally the influence of the chelator molecule, strong hyperfine coupling to the metal nucleus, and deuteration of the bulk matrix on DNP properties. At small Gd-DOTA concentrations the narrow central transition allows us to polarize nuclei with small gyromagnetic ratio such as (13)C and even (15)N via the solid effect. We demonstrate that enhancements observed are limited by the available microwave power and that large enhancement factors of >100 (for (1)H) and on the order of 1000 (for (13)C) can be achieved in the saturation limit even at 80 K. At larger Gd(iii) concentrations (≥10 mM) where dipolar couplings between two neighboring Gd(3+) complexes become substantial a transition towards cross effect as dominating DNP mechanism is observed. Furthermore, the slow spin-diffusion between (13)C and (15)N, respectively, allows for temporally resolved observation of enhanced polarization spreading from nuclei close to the paramagnetic ion towards nuclei further removed. Subsequently, we present preliminary DNP experiments on ubiquitin by site-directed spin-labeling with Gd(3+) chelator tags. The results hold promise towards applications of such paramagnetically labeled proteins for DNP applications in biophysical chemistry and/or structural biology.

  12. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

    PubMed

    Abdelkader, Hamdy; Longman, Michael; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

  13. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

    PubMed Central

    Alany, Raid G.

    2016-01-01

    Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation. PMID:27822337

  14. Structural and Magnetic Characterization of Superparamagnetic Iron Platinum Nanoparticle Contrast Agents for Magnetic Resonance Imaging

    PubMed Central

    Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Esch, Victor; Sillerud, Laurel O.

    2012-01-01

    We report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis (TGA), inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance (NMR) relaxivity at 4.7 Tesla. TEM showed that the diameters of the particles ranged from 9.3 nm to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of Octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependant on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A•m2/kg Fe. The measured relaxivities of the SIPPs at 4.7 Tesla were higher than commercially available superparamagnetic iron oxide nanoparticles (SPIONs), suggesting that these particles may be superior contrast agents in T2-weighted magnetic resonance imaging (MRI). PMID:22872817

  15. Structural and magnetic characterization of superparamagnetic iron platinum nanoparticle contrast agents for magnetic resonance imaging

    PubMed Central

    Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Esch, Victor; Sillerud, Laurel O.

    2012-01-01

    The authors report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis, inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance relaxivity at 4.7 T. TEM showed that the diameters of the particles ranged from 9.3 to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependent on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A·m2/kg Fe. The measured relaxivities of the SIPPs at 4.7 T were higher than commercially available superparamagnetic iron oxide nanoparticles, suggesting that these particles may be superior contrast agents in T2-weighted magnetic resonance imaging. PMID:25317380

  16. Shape control of the magnetic iron oxide nanoparticles under different chain length of reducing agents

    SciTech Connect

    Ngoi, Kuan Hoon; Chia, Chin-Hua Zakaria, Sarani; Chiu, Wee Siong

    2015-09-25

    We report on the effect of using reducing agents with different chain-length on the synthesis of iron oxide nanoparticles by thermal decomposition of iron (III) acetylacetonate in 1-octadecene. This modification allows us to control the shape of nanoparticles into spherical and cubic iron oxide nanoparticles. The highly monodisperse 14 nm spherical nanoparticles are obtained under 1,2-dodecanediol and average 14 nm edge-length cubic iron oxide nanoparticles are obtained under 1,2-tetradecanediol. The structural characterization such as transmission electron microscope (TEM) and X-ray diffraction (XRD) shows similar properties between two particles with different shapes. The vibrating sample magnetometer (VSM) shows no significant difference between spherical and cubic nanoparticles, which are 36 emu/g and 37 emu/g respectively and superparamagnetic in nature.

  17. Effect of iron on the biodistribution of bone scanning agents in humans

    SciTech Connect

    Choy, D.; Murray, I.P.C.; Hoschl, R.

    1981-07-01

    Nine patients with chronic iron overload, resulting from either repeated transfusions or hemochromatosis, had bone scans that were characterized by a reduction of bony uptake, marked increase in renal activity, and a significant increase in soft-tissue accumulation of /sup 99m/Tc-labeled bone-seeking agents. These findings were supported by semiquantitative computer analysis. The probable mechanisms of altered biodistribution and the possible role of serum ferritin are discussed. The importance of realizing the effect of excess iron on skeletal scintigraphy is further emphasized by the results of bone scanning in another patient in whom acute iron overload following infusion of iron-dextran resulted in excessive blood pool labeling.

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

    PubMed Central

    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

  19. Method and apparatus for back-extracting metal chelates

    DOEpatents

    Wai, C.M.; Smart, N.G.; Lin, Y.

    1998-08-11

    A method is described for extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered. 3 figs.

  20. Method and apparatus for back-extracting metal chelates

    DOEpatents

    Wai, Chien M.; Smart, Neil G.; Lin, Yuehe

    1998-01-01

    A method of extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered.

  1. Soil washing of chromium- and cadmium-contaminated sludge using acids and ethylenediaminetetra acetic acid chelating agent.

    PubMed

    Gitipour, Saeid; Ahmadi, Soheil; Madadian, Edris; Ardestani, Mojtaba

    2016-01-01

    In this research, the effect of soil washing in the removal of chromium- and cadmium-contaminated sludge samples collected from Pond 2 of the Tehran Oil Refinery was investigated. These metals are considered as hazardous substances for human health and the environment. The carcinogenicity of chromate dust has been established for a long time. Cadmium is also a potential environmental toxicant. This study was carried out by collecting sludge samples from different locations in Pond 2. Soil washing was conducted to treat the samples. Chemical agents, such as acetic acid, ethylenediaminetetra acetic acid (EDTA) and hydrochloric acid, were used as washing solutions to remove chromium and cadmium from sludge samples. The results of this study indicated that the highest removal efficiencies from the sludge samples were achieved using a 0.3 M HCl solution with 82.69% and 74.47% for chromium and cadmium, respectively. EDTA (0.1 M) in the best condition extracted 66.81% of cadmium and 72.52% of chromium from the sludges. The lowest efficiency values for the samples, however, were achieved using 3 M acetic acid with 41.7% and 46.96% removals for cadmium and chromium, respectively. The analysis of washed sludge indicated that the heavy metals removal decreased in the order of 3 M acetic acid < 0.1 M EDTA<0.3 M HCl, thus hydrochloric acid appears to offer a greater potential as a washing agent in remediating the sludge samples.

  2. The iron chelator Dp44mT suppresses osteosarcoma’s proliferation, invasion and migration: in vitro and in vivo

    PubMed Central

    Li, Pengcheng; Zheng, Xun; Shou, Kangquan; Niu, Yahui; Jian, Chao; Zhao, Yong; Yi, Wanrong; Hu, Xiang; Yu, Aixi

    2016-01-01

    Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells, including neuroblastoma, neuroepithelioma and prostate cancer. However, whether Dp44mT has anticancer effects in osteosarcoma is still unknown. Here, we investigated the antitumor action of Dp44mT in osteosarcoma and its underlying mechanisms. A human osteosarcoma 143B cell line in vitro and 143B xenograft in nude mice in vivo were utilized, the anticancer effects of Dp44mT were examined through methods of MTT assay, transwell, wound healing assay, flow cytometry, western blot, immunohistochemistry and H&E staining. We showed that Dp44mT inhibits cell proliferation, invasion and migration in vitro. In addition, flow cytometry further illustrated that Dp44mT suppression of 143B cell proliferation, invasion and migration were partially due to induction of cell apoptosis, cell cycle arrest in S phase and ROS production. Also in vitro and in vivo, the expression levels of Bcl2, Bax, Caspase3, Caspase9, LC3-II, β-catenin and its downstream targets such as C-myc and Cyclin D1 demonstrated that cell apoptosis and autophagy, as well as Wnt/β-catenin pathway were involved in Dp44mT induced osteosarcoma suppression. The Dp44mT inhibition of osteosarcoma was further verified via animal models. The findings indicated that in vivo Dp44mT showed a significant reduction in the 143B xenograft tumor growth and metastasis. In conclusion, our data demonstrated that Dp44mT has effective anticancer capability in osteosarcoma and that may represent a promising treatment strategy for osteosarcoma. PMID:28078009

  3. TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

    PubMed

    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.

  4. Novel double prodrugs of the iron chelator N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED): Synthesis, characterization, and investigation of activation by chemical hydrolysis and oxidation.

    PubMed

    Thiele, Nikki A; Abboud, Khalil A; Sloan, Kenneth B

    2016-08-08

    The development of iron chelators suitable for the chronic treatment of diseases where iron accumulation and subsequent oxidative stress are implicated in disease pathogenesis is an active area of research. The clinical use of the strong chelator N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and its alkyl ester prodrugs has been hindered by poor oral bioavailability and lack of conversion to the parent chelator, respectively. Here, we present novel double prodrugs of HBED that have the carboxylate and phenolate donors of HBED masked with carboxylate esters and boronic acids/esters, respectively. These double prodrugs were successfully synthesized as free bases (7a-f) or as dimesylate salts (8a-c,e), and were characterized by (1)H, (13)C, and (11)B NMR; MP; MS; and elemental analysis. The crystal structure of 8a was solved. Three of the double prodrugs (8a-c) were selected for further investigation into their abilities to convert to HBED by stepwise hydrolysis and H2O2 oxidation. The serial hydrolysis of the pinacol and methyl esters of N,N'-bis(2-boronic acid pinacol ester benzyl)ethylenediamine-N,N'-diacetic acid methyl ester dimesylate (8a) was verified by LC-MS. The macro half-lives for the hydrolyses of 8a-c, measured by UV, ranged from 3.8 to 26.3 h at 37 °C in pH 7.5 phosphate buffer containing 50% MeOH. 9, the product of hydrolysis of 8a-c and the intermediate in the conversion pathway, showed little-to-no affinity for iron or copper in UV competition experiments. 9 underwent a serial oxidative deboronation by H2O2 in N-methylmorpholine buffer to generate HBED (k = 10.3 M(-1) min(-1)). The requirement of this second step, oxidation, before conversion to the active chelator is complete may confer site specificity when only localized iron chelation is needed. Overall, these results provide proof of principle for the activation of the double prodrugs by chemical hydrolysis and H2O2 oxidation, and merit further investigation into the

  5. Compression and immersion tests and leaching of radionuclides, stable metals, and chelating agents from cement-solidified decontamination waste collected from nuclear power stations

    SciTech Connect

    Akers, D.W.; Kraft, N.C.; Mandler, J.W.

    1994-06-01

    A study was performed for the Nuclear Regulatory Commission (NRC) to evaluate structural stability and leachability of radionuclides, stable metals, and chelating agents from cement-solidified decontamination ion-exchange resin wastes collected from seven commercial boiling water reactors and one pressurized water reactor. The decontamination methods used at the reactors were the Can-Decon, AP/Citrox, Dow NS-1, and LOMI processes. Samples of untreated resin waste and solidified waste forms were subjected to immersion and compressive strength testing. Some waste-form samples were leach-tested using simulated groundwaters and simulated seawater for comparison with the deionized water tests that are normally performed to assess waste-form leachability. This report presents the results of these tests and assesses the effects of the various decontamination methods, waste form formulations, leachant chemical compositions, and pH of the leachant on the structural stability and leachability of the waste forms. Results indicate that releases from intact and degraded waste forms are similar and that the behavior of some radionuclides such as {sup 55}Fe, {sup 60}Co, and {sup 99}Tc were similar. In addition, the leachability indexes are greater than 6.0, which meets the requirement in the NRC`s ``Technical Position on Waste Form,`` Revision 1.

  6. Release of radionuclides and chelating agents from cement-solidified decontamination low-level radioactive waste collected from the Peach Bottom Atomic Power Station Unit 3

    SciTech Connect

    Akers, D.W.; Kraft, N.C.; Mandler, J.W.

    1994-03-01

    As part of a study being performed for the Nuclear Regulatory Commission (NRC), small-scale waste-form specimens were collected during a low oxidation-state transition-metal ion (LOMI)-nitric permanganate (NP)-LOMI solidification performed in October 1989 at the Peach Bottom Atomic Power Station Unit 3. The purpose of this program was to evaluate the performance of cement-solidified decontamination waste to meet the low-level waste stability requirements defined in the NRC`s ``Technical Position on Waste Form,`` Revision 1. The samples were acquired and tested because little data have been obtained on the physical stability of actual cement-solidified decontamination ion-exchange resin waste forms and on the leachability of radionuclides and chelating agents from those waste forms. The Peach Bottom waste-form specimens were subjected to compressive strength, immersion, and leach testing in accordance with the NRC`s ``Technical Position on Waste Form,`` Revision 1. Results of this study indicate that the specimens withstood the compression tests (>500 psi) before and after immersion testing and leaching, and that the leachability indexes for all radionuclides, including {sup 14}C, {sup 99}{Tc}, and {sup 129}I, are well above the leachability index requirement of 6.0, required by the NRC`s ``Technical Position on Waste Form,`` Revision 1.

  7. Poisoning of a Silica-Supported Cobalt Catalyst due to Presence of Sulfur Impurities in Syngas during Fischer–Tropsch Synthesis: Effects of Chelating Agent

    SciTech Connect

    Bambal, Ashish S.; Guggilla, Vidya S.; Kugler, Edwin L.; Gardner, Todd H.; Dadyburjor, Dady B.

    2014-04-09

    The effects of sulfur impurities on the performance of cobalt-based Fischer–Tropsch catalysts are evaluated under industrially relevant operating conditions of temperature, pressure, and impurity levels. Chelating agents (CAs) were used to modify the SiO2 support, and the performances of the CA-modified catalysts are compared with conventional Co/SiO2 catalysts. For both the Co/SiO2 and CA-modified catalysts, the presence of sulfur in the inlet syngas results in a notable drop in the CO conversion, an undesired shift in the hydrocarbon selectivity toward short-chain hydrocarbons, more olefins in the products, and lower product yields. In the post-poisoning stage, i.e., after termination of sulfur introduction in the inlet syngas, the CA-modified catalysts recover activity and selectivity (to some extent at least), whereas such trends are not observed for the base-case, i.e., unmodified Co/SiO2 catalyst. Finally, the improved performance of the CA-modified catalysts in the presence of sulfur is attributed to higher densities of active sites.

  8. Nanoparticle-based PARACEST agents: the quenching effect of silica nanoparticles on the CEST signal from surface-conjugated chelates.

    PubMed

    Evbuomwan, Osasere M; Merritt, Matthew E; Kiefer, Garry E; Dean Sherry, A

    2012-01-01

    Silica nanoparticles of average diameter 53 ± 3 nm were prepared using standard water-in-oil microemulsion methods. After conversion of the surface Si-OH groups to amino groups for further conjugation, the PARACEST agent, EuDOTA-(gly)₄ (-) was coupled to the amines via one or more side-chain carboxyl groups in an attempt to trap water molecules in the inner-sphere of the complex. Fluorescence and ICP analyses showed that approximately 1200 Eu(3+) complexes were attached to each silica nanoparticle, leaving behind excess protonated amino groups. CEST spectra of the modified silica nanoparticles showed that attachment of the EuDOTA-(gly)₄ (-) to the surface of the nanoparticles did not result in a decrease in water exchange kinetics as anticipated, but rather resulted in a complete elimination of the normal Eu(3+) -bound water exchange peak and broadening of the bulk water signal. This observation was traced to catalysis of proton exchange from the Eu(3+) -bound water molecule by excess positively charged amino groups on the surface of the nanoparticles.

  9. Luminescent lanthanide chelates and methods of use

    SciTech Connect

    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.

  10. Influence of chelator and near-infrared dye labeling on biocharacteristics of dual-labeled trastuzumab-based imaging agents

    PubMed Central

    Aldrich, Melissa B; Yang, Zhi; Zhou, Nina; Xie, Qing; Liu, Chen; Sevick-Muraca, Eva

    2016-01-01

    Objective To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111In- (DTPA)n-trastuzumab-(IRDye 800)m. Methods Trastuzumab-based conjugates were synthesized and conjugated with diethylenetriaminepentaacetic acid (DTPA) at molar ratios of 1, 2, 3 and 5 and with a fluorescent dye (IRDye 800CW) at molar ratios of 1, 3 and 5. Immunoreactivity and internalization were assessed on SKBR-3 cells, overexpressing human epidermal growth factor receptor 2. The stability in human serum and phosphate-buffered saline (PBS) was evaluated. The biodistribution of dual-labeled conjugates was compared with that of 111In-(DTPA)2-trastuzumab in a SKBR-3 xenograft model to evaluate the effect of dye-to-protein ratio. Results All trastuzumab-based conjugates exhibited a high level of chemical and optical purity. Flow cytometry results showed that increasing dye-to-protein ratios were associated with decreased immunoreactivity. Stability studies revealed that the conjugate was stable in PBS, while in human serum, increased degradation and protein precipitation were observed with increasing dye-to-protein ratios. At 4 h, the percentages of internalization of dual-labeled conjugates normalized by dye-to-protein ratio (m) were 24.88%±2.10%, 19.99%±0.59%, and 17.47%±1.26% for "m" equal to 1, 3, and 5, respectively. A biodistribution study revealed a progressive decrease in tumor uptake with an increase in the dye-to-protein ratios. The liver, spleen and kidney showed a marked uptake with increased dye-to-protein ratios, particularly in the latter. Conclusions With non-specific-site conjugation of the fluorescent dye with a protein based on imaging agent, the increase in dye-to-protein ratios negatively impacted the immunoreactivity and stability, indicating a reduced tumor uptake. PMID:27478322

  11. Evaluation of powdered infant formula milk as chelating agent for copper under simulated gastric conditions of a baby's stomach.

    PubMed

    Arancibia, Verónica; Peña, Claudia; Segura, Rodrigo

    2006-09-01

    The objective of this study was to determine the complexing capacity of four types of powdered commercial milks with copper(II) using square wave adsorptive stripping voltammetry. Two were types of cow milk adapted for babies under one year (A and B), one was soymilk (C) and the other was normal milk (D). Milk solutions were prepared following the instructions shown on the milk container, and they were mixed with a pepsin solution simulating a baby's stomach conditions (pepsin and salts concentration, pH and temperature). Complexing capacity was determined by titrating milk samples with aliquots of a standard copper solution until the peak current due to solvated or free copper ions was increasing. Assuming a 1:1 copper-milk complex, the apparent stability constant was found using the pseudopolarogram method. The log K'(Cu-milk) values were 4.9, 5.0, 3.0 and 5.1 for A, B, C and D types of milk, respectively. Voltammograms of the milk solution as a function of copper added show that the binding properties of the four types of powdered milk studied were different and that saturation of the four types, occurs at different copper concentrations. Concentrations obtained were: 4.9, 5.8, 1.1 and 10.1 mM for A, B, C and D types, respectively. The best complexing agent was the solution prepared with powdered milk D and the worst was that of C. This is important for the bioavailability of this element as a micronutrient.

  12. Beliefs about chelation among thalassemia patients

    PubMed Central

    2012-01-01

    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<0.001). Self-reported adherence to chelation was not associated with views about necessity or concerns, but negatively correlated with perceived sensitivity to DFO (Sensitive Soma scale; r=−0.23, p=0.01) and side effects of oral chelation (r=−0.14, p=0.04). High ferritin iron levels, potentially indicating lower adherence, were found in 41% of patients reporting low necessity of oral chelation compared to 24% reporting high necessity (p=0.048). Concerns about treatment were associated with lower quality of life and more symptoms of anxiety and depression. 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 PMID:23216870

  13. Post-transfusional iron overload in the haemoglobinopathies.

    PubMed

    Thuret, Isabelle

    2013-03-01

    In this report, we review the recent advances in evaluation and treatment of transfusional iron overload (IO). Results of the French thalassaemia registry are described. According to the disease, thalassaemia major or sickle cell anaemia, mechanisms and toxicity of iron overload, knowledge about IO long-term outcome and chelation treatment results, respective value of IO markers, differ. The recent tools evaluating organ specific IO and the diversification of iron chelator agents make possible to individualize chelation therapy in clinical practice. The severity of IO and the level of transfusional iron intake, the preferential localization of IO (heart/liver) as well as the tolerance and adherence profiles of the patient can now be taken into account. Introduction of cardiac magnetic resonance imaging for the quantification of myocardial iron and use of oral chelators have already been reported as decreasing the cardiac mortality rate related to IO in thalassaemia major patients. Long-term observation of patients under oral chelators will show if morbidity is also improving via a more continuous control of toxic iron and/or a better accessibility to cellular iron pools.

  14. Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics.

    PubMed

    Alwi, Rudolf; Telenkov, Sergey; Mandelis, Andreas; Leshuk, Timothy; Gu, Frank; Oladepo, Sulayman; Michaelian, Kirk

    2012-10-01

    In this study, we report for the first time the use of silica-coated superparamagnetic iron oxide nanoparticles (SPION) as contrast agents in biomedical photoacoustic imaging. Using frequency-domain photoacoustic correlation (the photoacoustic radar), we investigated the effects of nanoparticle size, concentration and biological media (e.g. serum, sheep blood) on the photoacoustic response in turbid media. Maximum detection depth and the minimum measurable SPION concentration were determined experimentally. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus and murine quadricept) was evaluated and the strong potential of silica-coated SPION as a possible photoacoustic contrast agents was demonstrated.

  15. Whole tissue AC susceptibility after superparamagnetic iron oxide contrast agent administration in a rat model

    NASA Astrophysics Data System (ADS)

    Lázaro, Francisco José; Gutiérrez, Lucía; Rosa Abadía, Ana; Soledad Romero, María; López, Antonio; Jesús Muñoz, María

    2007-04-01

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem ®), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers.

  16. The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1).

    PubMed

    Chen, Zhiqiang; Zhang, Daohai; Yue, Fei; Zheng, Minhua; Kovacevic, Zaklina; Richardson, Des R

    2012-05-18

    The epithelial-mesenchymal transition (EMT) is a key step for cancer cell migration, invasion, and metastasis. Transforming growth factor-β (TGF-β) regulates the EMT and the metastasis suppressor gene, N-myc downstream-regulated gene-1 (NDRG1), could play a role in regulating the TGF-β pathway. NDRG1 expression is markedly increased after chelator-mediated iron depletion via hypoxia-inducible factor 1α-dependent and independent pathways (Le, N. T. and Richardson, D. R. (2004) Blood 104, 2967-2975). Moreover, novel iron chelators show marked and selective anti-tumor activity and are a potential new class of anti-metabolites. Considering this, the current study investigated the relationship between NDRG1 and the EMT to examine if iron chelators can inhibit the EMT via NDRG1 up-regulation. We demonstrated that TGF-β induces the EMT in HT29 and DU145 cells. Further, the chelators, desferrioxamine (DFO) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), inhibited the TGF-β-induced EMT by maintaining E-cadherin and β-catenin, at the cell membrane. We then established stable clones with NDRG1 overexpression and knock-down in HT29 and DU145 cells. These data showed that NDRG1 overexpression maintained membrane E-cadherin and β-catenin and inhibited TGF-β-stimulated cell migration and invasion. Conversely, NDRG1 knock-down caused morphological changes from an epithelial- to fibroblastic-like phenotype and also increased migration and invasion, demonstrating NDRG1 knockdown induced the EMT and enhanced TGF-β effects. We also investigated the mechanisms involved and showed the TGF-β/SMAD and Wnt pathways were implicated in NDRG1 regulation of E-cadherin and β-catenin expression and translocation. This study demonstrates that chelators inhibit the TGF-β-induced EMT via a process consistent with NDRG1 up-regulation and elucidates the mechanism of their activity.

  17. Evaluation of the influence of the conjugation site of the chelator agent HYNIC to GLP1 antagonist radiotracer for insulinoma diagnosis.

    PubMed

    Faintuch, Bluma Linkowski; Seo, Daniele; Oliveira, Érica Aparecida De; Targino, Roselaine Campos; Moro, Ana Maria

    2017-01-26

    Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium-99m. Two different sites of the biomolecule were selected for chelator attachment. HYNIC-βAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). In conclusion the chelator position in the biomolecule influenced receptor uptake.

  18. Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson's disease and aging.

    PubMed

    Bar-Am, Orit; Amit, Tamar; Kupershmidt, Lana; Aluf, Yuval; Mechlovich, Danit; Kabha, Hoda; Danovitch, Lena; Zurawski, Vincent R; Youdim, Moussa B H; Weinreb, Orly

    2015-03-01

    Recently, we have designed and synthesized a novel multipotent, brain-permeable iron-chelating drug, VAR10303 (VAR), possessing both propargyl and monoamine oxidase (MAO) inhibitory moieties. The present study was undertaken to determine the multiple pharmacological activities of VAR in neurodegenerative preclinical models. We demonstrate that VAR affords iron chelating/iron-induced lipid-peroxidation inhibitory potency and brain selective MAO-A and MAO-B inhibitory effects, with only limited tyramine-cardiovascular potentiation of blood pressure. The results show that in 6-hydroxydopamine rat (neuroprotection) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse (neurorescue) Parkinson's disease models, VAR significantly attenuated the loss of striatal dopamine levels, markedly reduced dopamine turnover, and increased tyrosine-hydroxylase levels. Furthermore, chronic systemic treatment of aged rats with VAR improved cognitive behavior deficits and enhanced the expression levels of neurotrophic factors (e.g., brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor), Bcl-2 family members and synaptic plasticity in the hippocampus. Our study indicates that the multitarget compound VAR exerted neuroprotective and neurorestorative effects in animal models of Parkinson's disease and aging, further suggesting that a drug that can regulate multiple brain targets could be an ideal treatment-strategy for age-associated neurodegenerative disorders.

  19. NIR-activated iron oxides as a new multi-functional contrast agent of photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Ting, Pei-Hsien; Huang, Chih-Chia; Li, Meng-Lin

    2014-03-01

    Iron oxide nanoparticles are commonly used contrast agents for theranostic nanomedicines because of their advantages of good biocompatibility, high stability in physiological conditions, low cytotoxicity and excellent safety record in clinical settings for human use. In this study, we developed a NIR-activated iron oxide (NIR-Fe3O4) nanoparticle as a new multi-functional contrast agent of photoacoustic (PA) imaging. Unlike traditional iron oxides, the developed NIR-Fe3O4 owns biocompatibility and optical tunability capable of providing strong optical absorption in the NIR range for PA signal generation. Its intrinsic magnetic property enables the active magnetic tumor targeting. Phantom experiments were performed to confirm the tunability of NIR-Fe3O4's optical absorption in NIR and demonstrate its magnetic targeting capability. The PA signal response of NIR-Fe3O4 as a function of concentration was also investigated. The results showed that the PA signal of NIR-Fe3O4 with OD=1.25 was comparable to that of blood at 715 nm - the wavelength of peak absorption of the used NIR-Fe3O4. Moreover, the PA signal from NIR-Fe3O4 could be further improved by magnetic targeting. Overall, we proved that the potential of the developed NIR-Fe3O4 as a good tumor targeting contrast agent of PA imaging.

  20. Prevention of cell death by the zinc ion chelating agent TPEN in cultured PC12 cells exposed to Oxygen-Glucose Deprivation (OGD).

    PubMed

    Liu, Zhao; Huang, Yue-yang; Wang, Yu-xiang; Wang, Hong-gang; Deng, Fei; Heng, Bin; Xie, Lai-hua; Liu, Yan-qiang

    2015-01-01

    To elucidate the role of Zn(2+)-associated glutamate signaling pathway and voltage-dependent outward potassium ion currents in neuronal death induced by hypoxia-ischemia, PC12 cells were exposed to Oxygen-Glucose Deprivation (OGD) solution mimicking the hypoxic-ischemic condition in neuron, and the effect of N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a specific Zn(2+) chelating agent on OGD-induced neuronal death was assessed in the present study. The cell survival rate, apoptosis status, potassium channel currents, intracellular free glutamate concentration and GluR2 expression in PC12 cells exposed to OGD in the absence or presence of TPEN for different time were investigated. The results showed that OGD exposure increased apoptosis, reduced the cell viability (P < 0.01 at 3h, 6h and 24h, respectively compared to control), changed the voltage-dependent outward potassium ion current (increase at 1h, but decrease at 3h) and decreased the concentration of intracellular glutamate (P < 0.05 at 3h and 6h, P < 0.01 at 24h respectively compared to control) and GluR2 expression (P < 0.05 at 3h, 6h and 24h, respectively compared to control) in PC12 cells. TPEN partially reversed the influence resulted from OGD. These results suggest that OGD-induced cell apoptosis and/or death is mediated by the alteration in glutamate signaling pathway and the voltage-dependent outward potassium ion currents, while TPEN effectively prevent cell apoptosis and/or death under hypoxic-ischemic condition.

  1. Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and actinides.

    PubMed

    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.

  2. Iron oxide nanoparticles stabilized with dendritic polyglycerols as selective MRI contrast agents.

    PubMed

    Nordmeyer, Daniel; Stumpf, Patrick; Gröger, Dominic; Hofmann, Andreas; Enders, Sven; Riese, Sebastian B; Dernedde, Jens; Taupitz, Matthias; Rauch, Ursula; Haag, Rainer; Rühl, Eckart; Graf, Christina

    2014-08-21

    Monodisperse small iron oxide nanoparticles functionalized with dendritic polyglycerol (dPG) or dendritic polyglycerol sulfate (dPGS) are prepared. They are highly stable in aqueous solutions as well as physiological media. In particular, oleic acid capped iron oxide particles (core diameter = 11 ± 1 nm) were modified by a ligand exchange process in a one pot synthesis with dPG and dPGS bearing phosphonate as anchor groups. Dynamic light scattering measurements performed in water and different biological media demonstrate that the hydrodynamic diameter of the particles is only slightly increased by the ligand exchange process resulting in a final diameter of less than 30 nm and that the particles are stable in these media. It is also revealed by magnetic resonance studies that their magnetic relaxivity is reduced by the surface modification but it is still sufficient for high contrast magnetic resonance imaging (MRI). Additionally, incubation of dPGS functionalized iron oxide nanoparticles with human umbilical vein endothelial cells showed a 50% survival at 85 nM (concentration of nanoparticles). Surface plasmon resonance (SPR) studies demonstrate that the dPGS functionalized iron oxide nanoparticles inhibit L-selectin ligand binding whereas the particles containing only dPG do not show this effect. Experiments in a flow chamber with human myelogenous leukemia cells confirmed L-selectin inhibition of the dPGS functionalized iron oxide nanoparticles and with that the L-selectin mediated leukocyte adhesion. These results indicate that dPGS functionalized iron oxide nanoparticles are a promising contrast agent for inflamed tissue probed by MRI.

  3. Antiferromagnetic iron nanocolloids: a new generation in vivo T1 MRI contrast agent.

    PubMed

    Peng, Yung-Kang; Liu, Chien-Liang; Chen, Hsieh-Chih; Chou, Shang-Wei; Tseng, Wei-Hsuan; Tseng, Yu-Jui; Kang, Chia-Cheng; Hsiao, Jong-Kai; Chou, Pi-Tai

    2013-12-11

    A novel T1 agent, antiferromagnetic α-iron oxide-hydroxide (α-FeOOH) nanocolloids with a diameter of 2-3 nm, has been successfully prepared. These nanocolloids, together with a post synthetic strategy performed in mesoporous silica, are a great improvement over the low T1-weighted contrast common in traditional magnetic silica nanocomposites. The intrinsic antiferromagnetic goethite (α-FeOOH) shows very low magnetization (M(z)) of 0.05 emu g(-1) at H = 2 T at 300 K (0.0006 emu g(-1) for FeOOH/WMSN-PEG), which is 2 orders of magnitude smaller than any current ultrasmall iron oxide NPs (>5 emu g(-1)) reported to date, hence ensuring the low r2 (∝ Mz) (7.64 mM(-1) s(-1)) and r2/r1 ratio (2.03) at 4.7 T. These biodegradable α-FeOOH nanocolloids also demonstrate excellent in vitro cellular imaging and in vivo MR vascular and urinary trace imaging capability with outstanding biocompatibility, which is exceptionally well secreted by the kidney and not the liver as with most nanoparticles, opening up a new avenue for designing powerful antiferromagnetic iron T1 contrast agents.

  4. Potential water-quality effects from iron cyanide anticaking agents in road salt

    SciTech Connect

    Paschka, M.G.; Ghosh, R.S.; Dzombak, D.A.

    1999-10-01

    Water-soluble iron cyanide compounds are widely used as anticaking agents in road salt, which creates potential contamination of surface and groundwater with these compounds when the salt dissolves and is washed off roads in runoff. This paper presents a summary of available information on iron cyanide use in road salt and its potential effects on water quality. Also, estimates of total cyanide concentrations in snow-melt runoff from roadways are presented as simple mass-balance calculations. Although available information does not indicate a widespread problem, it also is clear that the water-quality effects of cyanide in road salt have not been examined much. Considering the large, and increasing, volume of road salt used for deicing, studies are needed to determine levels of total and free cyanide in surface and groundwater adjacent to salt storage facilities and along roads with open drainage ditches. Results could be combined with current knowledge of the fate and transport of cyanide to assess water-quality effects of iron cyanide anticaking agents used in road salt.

  5. Effects of solvent and chelating agent on synthesis of solid oxide fuel cell perovskite, La{sub 0.8}Sr{sub 0.2}CrO{sub 3-{delta}}

    SciTech Connect

    Lee, Byoung I.; Gupta, Ravindra K.; Whang, Chin M.

    2008-02-05

    Effects of solvent and chelating agent on synthesis of La{sub 0.8}Sr{sub 0.2}CrO{sub 3-{delta}} perovskite are reported. Samples are synthesized using a solvent (ethylene glycol or 2-methoxyethanol) and a chelating agent (acetylacetone, citric acid or ethylene diamine tetraacetic acid) by polymeric-gel method, and characterized by X-ray diffractometry and Fourier-transform infrared spectroscopy. Citric acid to metal cations molar ratio (Rc) is varied for ethylene glycol-citric acid system. Samples are mainly orthorhombic perovskite. SrCrO{sub 4} is appeared as a secondary phase and found to be the lowest for ethylene glycol-citric acid combination with Rc equal to 7. Crystallographic parameters of perovskite phase are determined and compared with those of LaCrO{sub 3}. A mechanism employing a partial-charge model, chelating effect and solvent-cage effect is proposed to explain the results. Effect of sintering temperature on phase, relative density and morphology of samples prepared using ethylene glycol and citric acid (Rc = 7) is also reported.

  6. Synthesis and characterization of superparamagnetic iron oxide nanoparticles as calcium-responsive MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Xu, Pengfei; Shen, Zhiwei; Zhang, Baolin; Wang, Jun; Wu, Renhua

    2016-12-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca2+) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca2+. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca2+. The T2 values decreased 25% when Ca2+ concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca2+-sensitive MRI.

  7. Poisoning of a silica supported cobalt catalyst due to the presence of sulfur impurities in syngas during Fischer-Tropsch synthesis: Effect of chelating agent

    SciTech Connect

    Bambal, A.S.; Gardner, T.H.; Kugler, E.L.; Dadyburjor, D.B.

    2012-01-01

    Sulfur compounds that are generally found in syngas derived from coal and biomass are a poison to Fischer-Tropsch (FT) catalysts. The presence of sulfur impurities in the ppm range can limit the life of a FT catalyst to a few hours or a few days. In this study, FT synthesis was carried out in a fixed-bed reactor at 230 °C, 20 bar, and 13,500 Ncm3/h/gcat for 72 h using syngas with H2/CO = 2.0. Cobalt-based catalysts were subjected to poisoning by 10 and 50 ppm sulfur in the syngas. The performance of FT catalyst was compared in context of syngas conversion, product selectivities and yields, during the poisoning as well as post-poisoning stages. At both the impurity concentrations, the sulfur was noted to cause permanent loss in the activity, possibly by adsorbing irreversibly on the surface. The sulfur poison affects the hydrogenation and the chain-propagation ability of the catalysts, and shifts the product selectivity towards short-chain hydrocarbons with higher percentages of olefins. Additional diffusion limitations caused due to sulfur poisoning are thought to alter the product selectivity. The shifts in product selectivities suggest that the sulfur decreases the ability of the catalyst to form C-C bonds to produce longer-chain hydrocarbons. The selective blocking of sulfur is thought to affect the hydrogenation ability on the catalyst, resulting in more olefins in the product after sulfur poisoning. The sulfur poisoning on the cobalt catalyst is expected to cause an increase in the number of sites responsible for WGS or to influence the Boudouard reaction, resulting in a higher CO2 selectivity. Both the sites responsible for CO adsorptions as well as the sites for chain growth are poisoned during the poisoning. Additionally, the performance of a base-case cobalt catalyst is compared with that of catalysts modified by chelating agents (CAs). The superior performance of CA-modified catalysts during sulfur poisoning is attributed to the presence of smaller

  8. Chelation of cadmium.

    PubMed Central

    Andersen, O

    1984-01-01

    The toxicity of cadmium is determined by chelation reactions: in vivo, Cd2+ exists exclusively in coordination complexes with biological ligands, or with administered chelating agents. The Cd2+ ion has some soft character, but it is not a typical soft ion. It has a high degree of polarizability, and its complexes with soft ligands have predominantly covalent bond characteristics. Cd2+ forms the most stable complexes with soft donor atoms (S much greater than N greater than 0). The coordination stereochemistry of Cd2+ is unusually varied, including coordination numbers from 2 to 8. Even though the Cd2+ ion is a d10 ion, disturbed coordination geometries are often seen. Generally, the stability of complexes increases with the number of coordination groups contributed by the ligand; consequently, complexes of Cd2+ with polydentate ligands containing SH groups are very stable. Cd2+ in metallothionein (MT) is coordinated with 4 thiolate groups, and the log stability constant is estimated to 25.5. Complexes between Cd2+ and low molecular weight monodentate or bidentate ligands, e.g., free amino acids (LMW-Cd), seem to exist very briefly, and Cd2+ is rapidly bound to high molecular weight proteins, mainly serum albumin. These complexes (HMW-Cd) are rapidly scavenged from blood, mainly by the liver, and Cd2+ is redistributed to MT. After about 1 day the Cd-MT complex (MT-Cd) almost exclusively accounts for the total retained dose of Cd2+, independent of the route of exposure. MT-Cd is slowly transferred to and accumulated in kidney cortex. The acute toxicity and interorgan distribution of parenterally administered Cd2+ are strongly influenced by preceding MT induction, or decreased capacity for MT synthesis; however, the gastrointestinal (GI) uptake of Cd2+ seems unaffected by preceding MT induction resulting in considerable capacity for Cd2+ chelation in intestinal mucosa, and this finding indicates that endogenous MT is not involved in Cd2+ absorption. The toxicity of

  9. VEGF-Iron Oxide Conjugate for Dual MR and PET Imaging of Breast Cancer Angiogenesis

    DTIC Science & Technology

    2007-09-01

    iron oxide nanoparticles conjugated with macrocyclic chelating agent DOTA for 64Cu-labeling and cyclic RGD peptide for integrin alpha (v)beta(3...Nanoparticles We have developed two types of novel superparamagentic iron oxide nanoparticles (USPIO), namely, PVP -IO and PASP-IO...Polyvinylpyrrolidone ( PVP )-coated iron oxide ( PVP -IO) nanoparticles were synthesized by a one-step thermal decomposition method (Fig. 3). The overall size of the

  10. TREG coated iron oxide nanoparticles as contrast agent for MRI in-vivo use

    NASA Astrophysics Data System (ADS)

    Gutierrez-Garcia, Eric; Hidalgo-Tobon, Silvia; Lopez, Ciro; Gonzalez-Rodriguez, Roberto; Coffer, Jeffery; De Celis Alonso, Benito; Dies Suarez, Pilar; Obregon, Manuel; Perez-Pena, Mario; Platas-Neri, Diana; Mendez-Rojas, Miguel

    2014-11-01

    Super-paramagnetic iron oxide nanoparticles (SPIONs) are of interest due to their great potential applications in diverse fields such as biomedicine. In this work we have prepared SPION nanoparticles using the polyol technique and characterized the magnetic properties of them for MRI in-vivo use. Nanoparticle preparation: All reagents were purchased from commercial sources (Sigma-Aldrich, St. Louis, USA) Iron (III) acetylacetonate, [Fe(acac)3], was used as the iron oxide precursor and thermally decomposed at high temperatures in triethyleneglycol (TREG). Nano-sized magnetite particles were prepared by an adaptation of the method proposed by Wei Cai et al[1-3]. A healthy rabbit was scanned on a clinical 1.5 T Philips MR scanner. Images were taken in 2D mode with a mFFE sequence. Relaxation time T2 was obtained from the MR images using a Matlab algorithm where the signal intensity decay was calculated at each image and then adjusted to a mono-exponential curve. Images were obtained before contrast injection, 24 hours and 36 hours following SPIONs administration. Signal decay at different Echo times for the prepared magnetic SPIONs, before and after contrast injection was measured. It was visualized a concentration of the agent contrast in brain and liver and the results were compared with images obtained from histopathology.

  11. Characterization and Functionalization of Iron-Oxide Nanoparticles for Use as Potential Agents for Cancer Thermotherapy

    NASA Astrophysics Data System (ADS)

    O'Reilly, Nora

    This thesis presents experimental studies of iron oxide nanoparticle synthesis, functionalization, and intracellular hyperthermal effects on murine macrophages as a model in vitro system. Colloidal suspensions of magnetic nanoparticles (MNPs) are of particular interest in Magnetic Fluid Hyperthermia (MFH). Iron oxide nanoparticles (IONPs) have garnered great interest as economical, biocompatible hyperthermia agents due to their superparamagnetic activity. Here we seek to optimize the synthetic reproducibility and in vitro utilization of IONPs for application in MFH. We compared aqueous synthetic protocols and various protective coating techniques using various analytical techniques and in vitro assays to assess the biocompatibility and feasibility of the various preparations of nanoparticles. Using a co-precipitation of iron salts methodology, iron oxide nanoparticles (IONPs) with an average diameter of 6-8nm were synthesized and stabilized with carboxylates. By performing calorimetry measurements in an oscillating magnetic field (OMF) with a frequency of 500 kHz and field strength of 0.008Tesla the superparamagnetic behavior of these particles was confirmed. To further investigate these IONPs in a biological application, citric acid-stabilized particles, in conjunction with heat generated by these IONPs when exposed to an OMF, were assessed to determine their effects on cell viability in a RAW 267.4 murine macrophage model system. Our results show that 91.5-97% of cells that have ingested IONPs die follow exposure to an OMF. Importantly, neither the IONPs (at applicable concentrations) nor the OMF show cytotoxic effects. These particular particles have promising preliminary results as hyperthermic agents in both the current literature and simple, proof-of-concept experiments in our laboratory setting. We present experimental results for the synthesis, characterization, and utilization of iron oxide nanoparticles in MFH. Our results show that while IONPs have

  12. Solid-phase materials for chelating metal ions and methods of making and using same

    DOEpatents

    Harrup, Mason K.; Wey, John E.; Peterson, Eric S.

    2003-06-10

    A solid material for recovering metal ions from aqueous streams, and methods of making and using the solid material, are disclosed. The solid material is made by covalently bonding a chelating agent to a silica-based solid, or in-situ condensing ceramic precursors along with the chelating agent to accomplish the covalent bonding. The chelating agent preferably comprises a oxime type chelating head, preferably a salicylaldoxime-type molecule, with an organic tail covalently bonded to the head. The hydrocarbon tail includes a carbon-carbon double bond, which is instrumental in the step of covalently bonding the tail to the silica-based solid or the in-situ condensation. The invented solid material may be contacted directly with aqueous streams containing metal ions, and is selective to ions such as copper (II) even in the presence of such ions as iron (III) and other materials that are present in earthen materials. The solid material with high selectivity to copper may be used to recover copper from mining and plating industry streams, to replace the costly and toxic solvent extraction steps of conventional copper processing.

  13. Determination of Ultra-trace Rhodium in Water Samples by Graphite Furnace Atomic Absorption Spectrometry after Cloud Point Extraction Using 2-(5-Iodo-2-Pyridylazo)-5-Dimethylaminoaniline as a Chelating Agent.

    PubMed

    Han, Quan; Huo, Yanyan; Wu, Jiangyan; He, Yaping; Yang, Xiaohui; Yang, Longhu

    2017-03-24

    A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating agent and the nonionic surfactant TritonX-114 was chosen as extractant. In a HAc-NaAc buffer solution at pH 5.5, Rh(III) reacts with 5-I-PADMA to form a stable chelate by heating in a boiling water bath for 10 min. Subsequently, the chelate is extracted into the surfactant phase and separated from bulk water. The factors affecting CPE were investigated. Under the optimized conditions, the calibration graph was linear in the range of 0.1-6.0 ng/mL, the detection limit was 0.023 ng/mL for rhodium and relative standard deviation was 3.67% (c = 1.0 ng/mL, n = 11).The method has been applied to the determination of trace rhodium in water samples with satisfactory results.

  14. Highly magnetic iron carbide nanoparticles as effective T2 contrast agents

    NASA Astrophysics Data System (ADS)

    Huang, Guoming; Hu, Juan; Zhang, Hui; Zhou, Zijian; Chi, Xiaoqin; Gao, Jinhao

    2013-12-01

    This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM-1 S-1, which is about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM-1 S-1). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications.This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM-1 S-1, which is about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM-1 S-1). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications. Electronic supplementary information (ESI) available: Supplementary figures and experimental details. See DOI: 10.1039/c3nr04691e

  15. Oxidative Stress, Redox Signaling, and Metal Chelation in Anthracycline Cardiotoxicity and Pharmacological Cardioprotection

    PubMed Central

    Popelová, Olga; Vávrová, Anna; Jirkovský, Eduard; Kovaříková, Petra; Geršl, Vladimír

    2013-01-01

    Abstract Significance: Anthracyclines (doxorubicin, daunorubicin, or epirubicin) rank among the most effective anticancer drugs, but their clinical usefulness is hampered by the risk of cardiotoxicity. The most feared are the chronic forms of cardiotoxicity, characterized by irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be complex, the pivotal role has been traditionally attributed to the iron-mediated formation of reactive oxygen species (ROS). In clinics, the bisdioxopiperazine agent dexrazoxane (ICRF-187) reduces the risk of anthracycline cardiotoxicity without a significant effect on response to chemotherapy. The prevailing concept describes dexrazoxane as a prodrug undergoing bioactivation to an iron-chelating agent ADR-925, which may inhibit anthracycline-induced ROS formation and oxidative damage to cardiomyocytes. Recent Advances: A considerable body of evidence points to mitochondria as the key targets for anthracycline cardiotoxicity, and therefore it could be also crucial for effective cardioprotection. Numerous antioxidants and several iron chelators have been tested in vitro and in vivo with variable outcomes. None of these compounds have matched or even surpassed the effectiveness of dexrazoxane in chronic anthracycline cardiotoxicity settings, despite being stronger chelators and/or antioxidants. Critical Issues: The interpretation of many findings is complicated by the heterogeneity of experimental models and frequent employment of acute high-dose treatments with limited translatability to clinical practice. Future Directions: Dexrazoxane may be the key to the enigma of anthracycline cardiotoxicity, and therefore it warrants further investigation, including the search for alternative/complementary modes of cardioprotective action beyond simple iron chelation. Antioxid. Redox Signal. 00, 000–000. PMID:22794198

  16. Iron

    MedlinePlus

    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 ...

  17. Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high

  18. Highly magnetic iron carbide nanoparticles as effective T(2) contrast agents.

    PubMed

    Huang, Guoming; Hu, Juan; Zhang, Hui; Zhou, Zijian; Chi, Xiaoqin; Gao, Jinhao

    2014-01-21

    This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM(-1) S(-1), which is about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM(-1) S(-1)). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications.

  19. Role of Coordination and Chelation in Utilization of Nutritionally Essential Trace Elements.

    DTIC Science & Technology

    BIOCHEMISTRY, *TRANSITION METALS), (*CHELATE COMPOUNDS, BIOCHEMISTRY), (*DIALYSIS, CHEMICAL ANALYSIS), NUTRITION , IRON, CHROMIUM, PHOSPHATES, AMINO ACIDS, HYDROXIDES, ALCOHOLS, PEPTIDES, MEMBRANES, LIQUID FILTERS

  20. The Crystal Structure of the Extracellular 11-heme Cytochrome UndA Reveals a Conserved 10-heme Motif and Defined Binding Site for Soluble Iron Chelates.

    SciTech Connect

    Edwards, Marcus; Hall, Andrea; Shi, Liang; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David; Clarke, Thomas A.

    2012-07-03

    Members of the genus Shewanella translocate deca- or undeca-heme cytochromes to the external cell surface thus enabling respiration using extracellular minerals and polynuclear Fe(III) chelates. The high resolution structure of the first undeca-heme outer membrane cytochrome, UndA, reveals a crossed heme chain with four potential electron ingress/egress sites arranged within four domains. Sequence and structural alignment of UndA and the deca-heme MtrF reveals the extra heme of UndA is inserted between MtrF hemes 6 and 7. The remaining UndA hemes can be superposed over the heme chain of the decaheme MtrF, suggesting that a ten heme core is conserved between outer membrane cytochromes. The UndA structure is the first outer membrane cytochrome to be crystallographically resolved in complex with substrates, an Fe(III)-nitrilotriacetate dimer or an Fe(III)-citrate trimer. The structural resolution of these UndA-Fe(III)-chelate complexes provides a rationale for previous kinetic measurements on UndA and other outer membrane cytochromes.

  1. Demetalation of Fe, Mn, and Cu chelates and complexes: application to the NMR analysis of micronutrient fertilizers.

    PubMed

    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.

  2. Relationship among Chelator Adherence, Change in Chelators, and Quality of Life in Thalassemia

    PubMed Central

    Trachtenberg, Felicia L.; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A.; Neufeld, Ellis J.; Yamashita, Robert

    2015-01-01

    Purpose Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of Health-Related Quality of Life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Methods Thalassemia Longitudinal Cohort participants in the US, UK, and Canada completed the SF-36v2 (ages 14+), and the PF-28 CHQ (parents of children<14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Results 258 adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8 years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly, due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from DFO infusion to oral deferasirox (p=0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical QOL. Conclusions Strategies to balance medical needs with family, work, and personal life may assist in adherence. PMID:24682717

  3. Legal considerations involving chemical control of iron and other deficiencies in plants

    SciTech Connect

    Wallace, A; Samman, Y. S.

    1981-01-01

    Four cases of lawsuits involving use of chelating agents in plant nutrition are discussed. Three of them involved use of iron. One concerned addition of FeDTPA to nursery trees in containers. One case involved foliar application of FeHEDTA to potatoes in July by airplane. Another case not involving iron chelate was with ZnEDTA and MnEDTA with Fe as FeSO/sub 4/ later as a foliar spray. The Zn and MnEDTA were applied as a band 8 inches (20 cm) on both sides of nursery tree rows just as the buds that had been placed in the fall began growing in the spring. In the fourth case, many tomato transplants died when the transplanting was done with about 120 ml per plant of transplant solution containing besides N, P and K, about 19 mg Zn as ZnEDTA, 14 mg Mn as MnEDTA and 7 mg Fe as FeHEDTA. Cases such as these will probably discourage use of chelating agents in plant nutrition even if the chelating agents were not the damaging agent. Not enough developmental work was done on the potential toxicities from metal chelates. This trend to lawsuits makes it even more important to solve iron chlorosis problems via plant breeding.

  4. Chemical Synthesis of Staphyloferrin B Affords Insight into the Molecular Structure, Iron Chelation, and Biological Activity of a Polycarboxylate Siderophore Deployed by the Human Pathogen Staphylococcus aureus.

    PubMed

    Madsen, Julie L H; Johnstone, Timothy C; Nolan, Elizabeth M

    2015-07-22

    Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.

  5. Radiolabeled iron in soybeans: intrinsic labeling and bioavailability of iron to rats from defatted flour

    SciTech Connect

    Weaver, C.M.; Schmitt, H.A.; Stuart, M.A.; Mason, A.C.; Meyer, N.R.; Elliott, J.G.

    1984-06-01

    Soybeans can be efficiently labeled with radiolabeled iron by supplying the iron via a nutrient culture medium as an iron salt or as a chelate. By using dual labeled iron and EDTA, it was determined that none of the chelator was transported to the shoots with the iron. Therefore, the use of chelated iron as the iron source in the nutrient medium should not affect assessments of bioavailability of iron from plants. Bioavailability (determined from whole-body retention curves of /sup 59/Fe in rats) of iron from defatted soy flour was relatively high and addition of vitamin C did not significantly enhance absorption of iron from defatted soy flour.

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

    PubMed

    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.

  7. 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.

    PubMed

    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 < 0.01). The birds supplemented with Met-TM and Yeast-TM consumed less feed than the NC and ITM-supplemented group (p < 0.001). Supplementation of trace elements irrespective of source increased the total ash content in the tibia (p < 0.001). However, concentration of Cu was lower in the Met-TM and Yeast-TM groups compared with the NC and the ITM groups (p < 0.05) although that of Fe, Mn and Zn was not affected at all by the dietary treatments. Total protein concentration in serum increased when either Met-TM or Yeast-TM was supplemented (p < 0.05) to the birds. Serum alkaline phosphatase activity, however, increased when the trace elements from either inorganic or organic sources were supplemented (p < 0.05). Compared with the ITM-supplemented group, excretion of Cu, Fe, Mn and Zn was lower in the birds supplemented with Met-TM or Yeast-TM, especially in the latter group (p < 0.05). The present experiment revealed that supplementation of broilers with methionine chelates or yeast proteinate forms of Cu, Fe, Mn and Zn improved body weight and feed conversion ratio (FCR) and markedly reduced

  8. Assessing bioavailability levels of metals in effluent-affected rivers: effect of Fe(III) and chelating agents on the distribution of metal speciation.

    PubMed

    Han, Shuping; Naito, Wataru; Masunaga, Shigeki

    To assess the effects of Fe(III) and anthropogenic ligands on the bioavailability of Ni, Cu, Zn, and Pb, concentrations of bioavailable metals were measured by the DGT (diffusive gradients in thin films) method in some urban rivers, and were compared with concentrations calculated by a chemical equilibrium model (WHAM 7.0). Assuming that dissolved Fe(III) (<0.45 μm membrane filtered) was in equilibrium with colloidal iron oxide, the WHAM 7.0 model estimated that bioavailable concentrations of Ni, Cu, and Zn were slightly higher than the corresponding values estimated assuming that dissolved Fe(III) was absent. In contrast, lower levels of free Pb were predicted by the WHAM 7.0 model when dissolved Fe(III) was included. Estimates showed that most of the dissolved Pb was present as colloidal iron-Pb complex. Ethylene-diamine-tetra-acetic acid (EDTA) concentrations at sampling sites were predicted from the relationship between EDTA and the calculated bioavailable concentration of Zn. When both colloidal iron and predicted EDTA concentrations were included in the WHAM 7.0 calculations, dissolved metals showed a strong tendency to form EDTA complexes, in the order Ni > Cu > Zn > Pb. With the inclusion of EDTA, bioavailable concentrations of Ni, Cu, and Zn predicted by WHAM 7.0 were different from those predicted considering only humic substances and colloidal iron.

  9. Chelation in root canal therapy reconsidered.

    PubMed

    Zehnder, Matthias; Schmidlin, Patrick; Sener, Beatrice; Waltimo, Tuomas

    2005-11-01

    The aim of this study was to assess interactions of EDTA and citric acid (CA) with sodium hypochlorite (NaOCl), the indispensable endodontic irrigant. Other chelators were simultaneously evaluated as possible alternatives: sodium triphosphate (STP), amino tris methylenephosphonic acid (ATMA), and 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP). Available chlorine was titrated in chelator-NaOCl solutions. All chelators other than HEBP and STP caused an almost complete, immediate loss of available chlorine in solution. Atomic absorbtion spectrometry and SEM evaluation of root canal walls of instrumented teeth indicated that NaOCl had no negative effect on calcium-complexing ability of chelators. STP was too weak a complexing agent to warrant further studies. Finally, CA-, EDTA-, and HEBP-NaOCl mixtures were evaluated for their antimicrobial capacity. Again, EDTA and CA negatively interfered with NaOCl, while HEBP did not.

  10. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T₂ Contrast Agents for MRI.

    PubMed

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-07-27

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.

  11. Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents.

    PubMed

    Di Marco, Mariagrazia; Sadun, Claudia; Port, Marc; Guilbert, Irene; Couvreur, Patrick; Dubernet, Catherine

    2007-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) particles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging. The coatings surrounding the USPIO inorganic core play a major role in both the in vitro stability and, over all, USPIO's in vivo fate. Different physicochemical properties such as final size, surface charge and coating density are key factors in this respect. Up to now no precise structure--activity relationship has been described to predict entirely the USPIOs stability, as well as their pharmacokinetics and their safety. This review is focused on both the classical and the latest available techniques allowing a better insight in the magnetic core structure and the organic surface of these particles. Concurrently, this work clearly shows the difficulty to obtain a complete physicochemical characterization of USPI