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Iron chelation

George A Alexiou, Paraskevi Gerogianni, Evrysthenis Vartholomatos, Athanasios P Kyritsis
Glioblastoma is the most malignant primary brain tumor with a median survival of 15 months. Temozolomide (TMZ) is the standard of care for these patients. Iron chelators have been shown to have anti-tumor activity; however, deferiprone (DFP), an orally administered iron chelator, has not been previously evaluated in gliomas. In the present study, we found that combination treatment in glioma cells with TMZ and DFP significantly reduced cell viability, produced cell cycle arrest at G2/M phase, and enhanced apoptosis...
October 21, 2016: Cancer Investigation
Marzieh Zargaran, Ebrahim Saadat, Rassoul Dinarvand, Mohammad Sharifzadeh, Farid Dorkoosh
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...
September 2016: Advanced Pharmaceutical Bulletin
Eirini Lioudaki, Martin Whyte
Patients with higher liver iron stores are likely to have a worse cardiac outcome following noncompliance with chelation. Cardiovascular magnetic resonance identifies myocardial siderosis allowing optimization of iron chelation regimes. Diabetes puts thalassemic patients at increased risk of myocardial fibrosis. Dual chelation therapy with deferoxamine and deferiprone offers improved cardiac outcomes.
October 2016: Clinical Case Reports
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris
Pancreatic dysfunction during diabetes is linked to the induction of endoplasmic reticulum (ER) stress on pancreatic beta (β) cells. Our laboratory recently discovered that p21 protects from diabetes by modifying the outcome of ER stress response. In the present study, we explored the antidiabetic activity of ciclopirox (CPX), an iron chelator and recently described activator of p21 expression. The effects of CPX in beta cell survival and function were assessed in cultured islets in vitro as well as in diabetic mice in vivo...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Rahul Pal, Saif Hameed, Sharda Sharma, Zeeshan Fatima
Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB...
October 15, 2016: Brazilian Journal of Infectious Diseases
Qing Zhang, Haoyu Zhao, Dong Li, Liping Liu, Shuhu Du
To achieve drug targeting and on-demand releasing, surface functionalization plays a critical role in fabricating potential mesoporous silica nanoparticles (MSNs) toward tumor chemotherapy. Here, we prepared a size-controllable ligand-functionalized MSNs delivery system via coordinate bonding, which can release doxorubicin (DOX) in response to pH and prolong the circulation time of drug in vivo. After modifying the external surface of MSNs with polyethylene glycol (PEG), iminodiacetic acid (IDA) as a ligand was mainly grafted on the surface of mesopores to chelate cupric iron and DOX in sequence via coordinate bonds...
October 11, 2016: Colloids and Surfaces. B, Biointerfaces
Angela Vitrano, Giuseppina Calvaruso, Eliana Lai, Grazia Colletta, Alessandra Quota, Calogera Gerardi, Luciana Concetta Rigoli, Lorella Pitrolo, Liana Cuccia, Francesco Gagliardotto, Aldo Filosa, Vincenzo Caruso, Crocetta Argento, Saveria Campisi, Michele Rizzo, Luciano Prossomariti, Carmelo Fidone, Maria Fustaneo, Rosario Di Maggio, Aurelio Maggio
In the last few decades, the life expectancy of regularly transfused β-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with β-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death...
October 17, 2016: British Journal of Haematology
Fatima Setifi, Dohyun Moon, Robeyns Koen, Zouaoui Setifi, Morad Lamsayah, Rachid Touzani
The search for new mol-ecular materials with inter-esting magnetic properties using the pseudohalide azide ion and quinolin-8-amine (aqin, C9H8N2) as a chelating ligand, led to the synthesis and structure determination of the title complex, [Fe(N3)2(C9H8N2)2]. The complex shows an octa-hedral geometry, with the Fe(II) atom surrounded by six N atoms; the two N3(-) anions coordinate in a cis configuration, while the remaining N atoms originate from the two quinolin-8-amine ligands with the quinoline N atoms lying on opposite sides of the Fe atom...
October 1, 2016: Acta Crystallographica. Section E, Crystallographic Communications
Pavlína Hašková, Hana Jansová, Jan Bureš, Miloslav Macháček, Anna Jirkovská, Katherine J Franz, Petra Kovaříková, Tomáš Šimůnek
Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis...
October 12, 2016: Toxicology
Thomas Walker, Christos Michaelides, Antigoni Ekonomou, Kalotina Geraki, Harold G Parkes, Maria Suessmilch, Amy H Herlihy, William R Crum, Po-Wah So
Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN)...
October 12, 2016: Aging
Ditte B Hermund, Ayse Karadag, Ulf Andersen, Rósa Jónsdóttir, Hordur G Kristinsson, Cesarettin Alasalvar, Charlotte Jacobsen
Fucus vesiculosus extracts that have both radical scavenging activity and metal chelating ability in vitro were used as natural antioxidant in granola bars enriched with fish oil emulsion either by using primary and secondary emulsion systems stabilized by sodium caseinate alone and sodium caseinate-chitosan. The bars were stored at 20°C and evaluated over a period of 10 weeks by measuring the development of primary and secondary oxidation products. The samples prepared with secondary emulsion system developed less oxidation products probably due to increased interfacial layer thickness that would act a barrier to the penetration and diffusion of molecular species that promote oxidation...
October 14, 2016: Journal of Agricultural and Food Chemistry
Akinobu Ito, Toru Nishikawa, Shuhei Matsumoto, Hidenori Yoshizawa, Takafumi Sato, Rio Nakamura, Masakatsu Tsuji, Yoshinori Yamano
Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the 3(rd)-position side chain. The in vitro activity of cefiderocol against Pseudomonas aeruginosa was enhanced in the iron-depleted condition where that of ceftazidime was not affected. The monitoring of [Thiazole-(14)C]-cefiderocol revealed the increased intracellular accumulation of cefiderocol in the P. aeruginosa cells incubated under iron-depleted condition compared with those incubated under iron-sufficient condition...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Joy Benadiba, Celia Rosilio, Marielle Nebout, Vera Heimeroth, Zouhour Neffati, Alexandra Popa, Didier Mary, Emmanuel Griessinger, Véronique Imbert, Nicolas Sirvent, Jean-François Peyron
Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis...
October 13, 2016: Leukemia & Lymphoma
Raschida R Bouhouch, Sana El-Fadeli, Maria Andersson, Abdelmounaim Aboussad, Laila Chabaa, Christophe Zeder, Maria Kippler, Jeannine Baumgartner, Azzedine Sedki, Michael B Zimmermann
BACKGROUND: Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES: Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition...
October 12, 2016: American Journal of Clinical Nutrition
Yuping Li, Ke Pan, Lin Chen, Jiao-Lin Ning, Xiaojun Li, Ting Yang, Niccolò Terrando, Jianteng Gu, Guocai Tao
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD...
October 12, 2016: Journal of Neuroinflammation
Daniel Załuski, Helena D Smolarz
The chemical composition and pharmacological activity of E. senticosus cultivated in Poland were investigated. Studies included the assay of TPC and TFC, 2D-TLC identification of phenolic acids, HPTLC-detection of antioxidants, and antioxidative, antileukemic, anti-MMPs properties of E. senticosus. The ethanolic extracts from the roots, spring leaves, fruits, and the chloroform extract from the roots were tested. The richest in polyphenols are the fresh fruits (57.5 mg/g), while in flavonoids the spring leaves (27...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Tomoko Abe, Yoshiteru Hashimoto, Sayaka Sugimoto, Kenta Kobayashi, Takuto Kumano, Michihiko Kobayashi
The adenylation domain of nonribosomal peptide synthetase (NRPS) is responsible for the selective substrate recognition and its activation (as an acyl-O-AMP intermediate) during ATP consumption. DhbE, a stand-alone adenylation domain, acts on an aromatic acid, 2,3-dihydroxybenzoic acid (DHB). This activation is the initial step of the synthesis of bacillibactin that is a high-affinity small-molecule iron chelator also termed siderophore. Subsequently, the activated DHB is transferred and attached covalently to a peptidyl carrier protein domain via a thioester bond...
October 12, 2016: Journal of Antibiotics
Monia Ouederni, Monia Ben Khaled, Fethi Mellouli, Elhem Ben Fraj, Nawel Dhouib, Ismehen Ben Yakoub, Selem Abbes, Nejla Mnif, Mohamed Bejaoui
Thalassemia is a common genetic disorder in Tunisia. Early iron concentration assessment is a crucial and challenging issue. Most of annual deaths due to iron overload occurred in underdeveloped regions of the world. Limited access to liver and heart MRI monitoring might partially explain these poor prognostic results. Standard software programs are not available in Tunisia. This study is the first to evaluate iron overload in heart and liver using the MRI T2* with excel spreadsheet for post processing. Association of this MRI tool results to serum ferritin level, and echocardiography was also investigated...
October 12, 2016: Annals of Hematology
Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim
PURPOSE: Alpha lipoic acid (ALA) is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. PATIENTS AND METHODS: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time...
2016: Clinical Ophthalmology
Kensuke Usuki
Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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