Chelator Concentration Research Articles

Pressure-assisted chelation extraction of lead from contaminated soil

Soil contamination by metallic elements including lead occurs frequently. Contaminant metals in soil pose a serious risk to public health and groundwater supplies. Extraction using chelants is seen as a remediation option; however, it is often hampered by access to the contaminants that are shielded by the soil matrix. We have developed a novel extraction technique that utilizes a mildly elevated pressure in consecutive cycles of compression and decompression along with a chelating agent for the soil slurry. Complete extraction of 3300 mg/kg of Pb from soil was achieved by 100 mM of EDTA (ethylenediaminetetraacetic acid) in 10 min using 20 pressure cycles at 150 psi (10 atm). Extraction was studied according to pressure, number of pressure cycles, chelant concentration, solid content, pH, agitation, and use of consecutive washings. Heightened extraction is attributed to fracturing of the soil particles that leads to enhanced contaminant exposure to the chelating agent.

Preparation of Titania Film by Vapor Decomposition of Chelated Tetrabutyl Titanate

The vapor decomposition of chelated tetrabutyl titanate on glass substrate was used for the preparation of titania films. The influences of decomposition temperature, chelant concentration on the photocatalytic properties of titania film were investigated. The films were characterized by XRD, ATR and the precursor solution was characterized by DTA.

Nanodomain Coupling between Ca2+ Channels and Ca2+ Sensors Promotes Fast and Efficient Transmitter Release at a Cortical GABAergic Synapse

It is generally thought that transmitter release at mammalian central synapses is triggered by Ca2+ microdomains, implying loose coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis. Here we show that Ca2+ channel subunit immunoreactivity is highly concentrated in the active zone of GABAergic presynaptic terminals of putative parvalbumin-containing basket cells in the hippocampus. Paired recording combined with presynaptic patch pipette perfusion revealed that GABA release at basket cell-granule cell synapses is sensitive to millimolar concentrations of the fast Ca2+ chelator BAPTA but insensitive to the slow Ca2+ chelator EGTA. These results show that Ca2+ source and Ca2+ sensor are tightly coupled at this synapse, with distances in the range of 10-20 nm. Models of Ca2+ inflow-exocytosis coupling further reveal that the tightness of coupling increases efficacy, speed, and temporal precision of transmitter release. Thus, tight coupling contributes to fast feedforward and feedback inhibition in the hippocampal network.

EFFECT OF EASILY BIODEGRADABLE AMENDMENTS ON HEAVY METAL SOLUBILIZATION AND ACCUMULATION IN TECHNICAL CROPS - A FIELD TRIAL

Abstract Heavy‐metal soil pollution is a common environmental problem all over the world. In the induced phytoextraction process plants can transport and translocate to their above‐ground tissues significant concentration of contaminants. Since some heavy metals are mostly presented in non‐soluble state, the application of chelating agents is needed. In this study we introduced into the rhizosphere of maize (var. Kneja 530) and sunflower (var. Favorit) plants 1 and 5 mmol l−1 of EDDS and NTA, and 5 g kg−1 of nutrients to enhance the accumulated concentrations of cadmium, lead and zinc. The fraction of CaCl2‐extractable metals increased incrementing the concentration of chelates. This was clearly pronounced for all the metals in the treatments with NTA and for Pb in those with EDDS. Generally, under all the experimental conditions the accumulated heavy‐metal concentrations were found to be significantly higher than in the control. Thus, in the case of higher concentration of NTA and EDDS, the accumulated C...

EFFECT OF EASILY BIODEGRADABLE AMENDMENTS ON HEAVY METAL SOLUBILIZATION AND ACCUMULATION IN TECHNICAL CROPS ‐ A FIELD TRIAL

Heavy‐metal soil pollution is a common environmental problem all over the world. In the induced phytoextraction process plants can transport and translocate to their above‐ground tissues significant concentration of contaminants. Since some heavy metals are mostly presented in non‐soluble state, the application of chelating agents is needed. In this study we introduced into the rhizosphere of maize (var. Kneja 530) and sunflower (var. Favorit) plants 1 and 5 mmol l−1 of EDDS and NTA, and 5 g kg−1 of nutrients to enhance the accumulated concentrations of cadmium, lead and zinc. The fraction of CaCl2‐extractable metals increased incrementing the concentration of chelates. This was clearly pronounced for all the metals in the treatments with NTA and for Pb in those with EDDS. Generally, under all the experimental conditions the accumulated heavy‐metal concentrations were found to be significantly higher than in the control. Thus, in the case of higher concentration of NTA and EDDS, the accumulated Cd in the leaves of sunflower was found to be threefold higher. The highest accumulation of Pb in the leaves of maize was observed when nutrients were added (62 mg kg−1). On the other hand, negative effects of the used chelating agents on soil bacteria and fungi at plant harvest were not observed. Moreover, when nutrients were added, the number of studied microorganisms significantly increased.

Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy

Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe-HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at 'shuttling' iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators.

Growth of Ag nanoparticles using plasma-modified multi-walled carbon nanotubes

This study presents a novel method for preparing multi-walled carbon nanotubes(MWNTs) grafted with a poly(2-hydroxyethyl methacrylate) (HEMA)–silver complex(CNTs–HEMA–Ag complex) through plasma-induced grafting polymerization. Thecharacteristics of the MWNTs after being grafted with HEMA polymer are monitored byFourier transform infrared (FT-IR) spectroscopy. The chelating groups in the HEMApolymer grafted on the surface of the CNTs–HEMA are the coordination sites forchelating silver ions, and are further used as nanotemplates for the growing of Agnanoparticles (quantum dots). Transmission electron microscopy (TEM) revealsthat the particle size of Ag nanoparticles on the CNT surfaces increases with theAg+ chelating concentration, reaction time, and reaction temperature. Moreover, thecrystalline phase of Ag nanoparticles is identified by using x-ray diffraction(XRD). In addition, high-resolution x-ray photoelectron spectroscopy (XPS) isused to characterize the functional groups on the surface of the MWNTs afterchemical modification through plasma treatment; it demonstrates that thegrowing amount of the Ag nanoparticles on the nanotubes increases with theAg+ chelating concentration due to the blocking effect of the Ag particles forming on theMWNTs.

Enzyme-based control of oxalic acid in the pulp and paper industry

Enzymatically catalyzed decomposition of oxalic acid in bleaching filtrates from the pulp and paper industry offers a possibility to enduringly prevent oxalate scaling problems by specific removal of the oxalic acid in the system rather than by attempting to avoid calcium oxalate precipitation by countermeasures aiming at improved solubility. To achieve a broad evaluation of various oxalate-degrading enzymes and to cover conditions encountered in various types of processes, 16 different bleaching filtrates were collected from pulp mills engaged in mechanical pulping of softwood, mechanical pulping of aspen, and kraft pulping of softwood. A novel oxalate-degrading enzyme provided by Novozymes was compared with commercially available oxalate oxidase from barley and oxalate decarboxylase from Aspergillus niger. The activity of the enzymes in the filtrates was investigated using kinetic analysis and multivariate data analysis. Kinetic analysis indicated that the degradation rates were governed more by inhibitors in the filtrates than by the concentration of oxalic acid. Multivariate data analysis suggested links between high concentrations of certain compounds in the filtrates and high or low enzyme activity, as exemplified by the link between high concentrations of chelators in filtrates from mechanical pulping and low activity of oxalate oxidase from barley. All three enzymes could degrade oxalic acid in all filtrates, despite the fact that very high concentrations of residual hydrogen peroxide were found in several of the filtrates.

Ca 2+-independent effects of BAPTA and EGTA on single-channel Cl − currents in brown adipocytes

The Cl − channels of brown adipocytes electrophysiologically resemble outwardly rectifying Cl − channels (ORCC). To study tentative Ca 2+ regulation of these channels, we attempted to control Ca 2+ levels at the cytoplasmic side of the inside-out membrane patches with Ca 2+-chelating agents. However, we found that the commonly used Ca 2+-chelators EGTA and BAPTA by themselves influenced the Cl − channel currents, unrelated to their calcium chelating effects. Consequently, in this report we delineate effects of Ca 2+-chelators (acting from the cytoplasmic side) on the single Cl − channel currents in patch-clamp experiments. Using fixed (1–2 mM) concentrations of chelators, two types of Cl − channels were identified, as discriminated by their reaction to the Ca 2+-chelators and by their conductance: true-blockage channels (31 pS) and quasi-blockage channels (52 pS). In true-blockage channels, EGTA and BAPTA inhibited channel activity in a classical flickery type manner. In quasi-blockage channels, chelators significantly shortened the duration of individual openings, as in a flickering block, but the overall channel activity tended to increase. This dual effect of mean open time decrease accompanied by a tendency of open probability to increase we termed a quasi-blockage. Despite the complications due to the chelators as such, we could detect a moderate inhibitory effect of Ca 2+. The anionic classical Cl − channel blockers DIDS and SITS could mimic the true/quasi blockage of EGTA and BAPTA. It was concluded that at least in this experimental system, standard techniques for Ca 2+ level control in themselves could fundamentally affect the behaviour of Cl − channels.

The role of citric acid in cadmium and nickel uptake and translocation, in Halimione portulacoides

Some plants have high ability to absorb heavy metals in high concentrations. In this study, Halimione portulacoides was tested in conjunction with citric acid, in order to evaluate the possible use of this plant in phytoremediation processes in salt marshes. Two different concentrations of chelator were used combined with two heavy metal concentrations. When 25 μM of citric acid was applied, Cd uptake and translocation was enhanced while for Ni these processes were almost inhibited. Increasing citric acid concentration to 50 μM, Ni absorption decreased by the roots while for Cd there was still an increase in root uptake. Analysing translocation with this concentration of chelator, a decreased metal content in the upper organs for both metals was observed. While for Cd an optimal concentration of 25 μM of citric acid was observed for phytoremediative processes, for nickel neither concentrations of chelator showed advantages for application in this remediative method.

Demineralizing Action of EGTA in Endodontics

The demineralization of dentin obtained by treatment with a chelating agent ethylene diamminotetracetic acid (EDTA) or ethylene glycol-bis(beta-aminoethyl ether)-N-tetraacetic acid (EGTA), is a dynamic process involving chelation and solubilization. The actions of the EDTA and EGTA on dentin are influenced by the pH. Increasing mM concentrations of EDTA or EGTA the equivalent pH decreases in a similar slope to 80 mM chelator concentration. Increasing the chelator concentration different data were obtained: with EGTA the pH decreases slightly while with EDTA goes back up to the initial values. After 80 mM, EDTA reduces the activity on the dentin, and EGTA continues to work at higher concentrations. We demonstrated that EGTA solubilized more of 60 percent of dentin while EDTA gives about 20% at the maximal of the solubility.

Heavy metals mobilization from harbour sediments using EDTA and citric acid as chelating agents

In this paper experimental tests of heavy metals mobilization from sediments collected from an Italian harbour are presented and discussed. Batch tests of washing with an aqueous solution of chelating agent were performed at selected liquid/solid (L/S) ratios and chelant concentration (0.01, 0.05 and 0.1 M). Two chelating agents were chosen: EDTA and citric acid. The objective of the tests was to investigate metal mobilization and soil mineral dissolution promoted by the washing treatment. The study was focused on the mobilization of Pb, Zn, and Cu: their concentrations in the contact solution, together with Fe and Ca concentration, were monitored along time for 144 h. Results of experimental tests performed at different chelant concentration and L/S ratio show EDTA effectiveness in mobilizing metals bond to the sediment. The overall amount of the three selected metals (Cu, Pb and Zn) extracted in the tests with EDTA varied in a quite narrow range (from 2.262 to 2.724 mmol), while the higher was the EDTA concentration in the washing solution, the higher the dissolution of other competitive cations, such as Ca and Fe. In addition, a general difficulty in copper extraction from the organic fraction of the sediment was observed, due to the high stability of copper humate. The mechanism of metals extraction was found to involve the initial metals salts dissolution, that was pH-dependant, followed by the development of exchange reactions between the metal–EDTA complexes previously formed. Depending upon the pH of the washing solution an initial high Ca dissolution was observed, followed by dramatic reduction in Ca 2+ content, mainly determined by calcium carbonate precipitation, as a result of the increase of pH during mixing. Metal mobilization was evaluated performing sequential extraction tests: the dissolution of Cu, Pb and Zn from the carbonate fraction of the sediment was almost total, as the mobilization of Pb and Zn from the Fe–Mn oxides and hydroxides fraction. On the contrary, as a consequence of the mobilization induced by washing treatment, about 17% of the remaining Cu and 10% of the remaining Zn resulted in the exchangeable fraction. At the investigated operating conditions, citric acid was unable to extract Pb and Cu from the sediment, while at the strong acidic conditions maintained during the extractions with citric acid, a Zn mobilization up to the 80% of the initial amount was observed, depending upon the operating conditions in the extractions. In addition, because of the great affinity between citric acid and Fe, and the strong acidic conditions maintained during extraction, a high Fe dissolution was observed (up to about the 39% of the total Fe content in the sediment).

Phospholipase Action of Platelet-activating Factor Acetylhydrolase, but Not Paraoxonase-1, on Long Fatty Acyl Chain Phospholipid Hydroperoxides

Phospholipid hydroperoxide (PLOOH) degrading activity of high density lipoprotein (HDL)-derived paraoxonase-1 (PON1) was investigated, using peroxidized 1-palmitoyl-2-oleoyl phosphatidylcholine (PCOOH) as substrate and high performance thin layer chromatography for quantitative peroxide analysis. Incubation of PCOOH with PON1 resulted in decay of the latter and reciprocal buildup of oleic acid hydroperoxide (OAOOH) at rates unaffected by GSH or other reductants. A serine esterase inhibitor blocked this activity and a recombinant PON1 was devoid of it, raising the possibility that the activity represents platelet-activating factor acetylhydrolase (PAF-AH), an esterase that co-purifies with PON1 from HDL. This was verified by showing that a recombinant PAF-AH recapitulates the ability of natural PON1 to hydrolyze PCOOH and release OAOOH while having essentially no effect on parental PC. Furthermore, recombinant PAF-AH and natural PON1 were shown to have similar K(m) values for PCOOH hydrolysis. Finally, we found that recombinant PAF-AH, but not PON1, catalyzes PLOOH hydrolysis in peroxidized low density lipoprotein. We conclude from this study that PON1 is neither a PLOOH peroxidase nor hydrolase and that the phospholipase A(2)-like activity previously attributed to PON1 in natural enzyme preparations was actually due to novel PLOOH hydrolytic activity of contaminating PAF-AH.

Mechanism of 2-Deoxy-D-ribose-induced Damage in Pancreatic β-cells

Background: Mechanism for glucose toxicity is known to be an increased oxidative stress produced by multiple pathways. In our previous report, 2-deoxy-d-ribose (dRib) promoted apoptosis by increasing oxidative stress in a pancreatic β-cell line. We performed this study to investigate the mechanism of dRib-induced damage of β-cells. Methods: HIT-T15 cells were cultured in RPMI-1640 medium with 40 mM dRib for 24 hours after pretreatment with various concentrations of a metal chelator (DTPA) and inhibitors of protein glycation (aminoguanidine and pyridoxamine). Cell viability was determined by MTT assay. Apoptosis was analyzed by flow cytometry with annexin V/PI double staining.Results: DTPA, which inhibits the monosaccharide autoxidation, partially reversed dRib-induced cytotoxicity in a dose-dependent manner (P

Screening of secreted proteases of Paenibacillus larvae by using substrate-SDS-polyacrylamide gel electrophoresis

SummaryThis study is focused on a primary proteolytic screening of the secreted products of P. larvae cultures by means of substrate SDS-PAGE and using specific inhibitors for the determination of protease classes. Two- and five-day cultures (cultivation medium: MYPGP broth) were used for primary screening. Proteolytic activity was detected only in gels containing gelatin in the area of 87, 74 and 42 kDa in two-day culture and in the area of 87,74,42 and 40 kDa in five-day culture. By using various protease inhibitors, it was considered that the 87 and 74 kDa stable proteases (most active at pH 7) presented in two-day and five-day culture can be metalloproteases, by virtue of their sensitivity to EDTA, 1, 10-phenantroline and EGTA (metal chelators) in standard concentrations, and by the lack of sensitivity to inhibitors of the other classes of protease. The 40 kDa protease in two-day culture was inhibited also by standard concentration of metal chelators, and was most active at pH 6. The 40 and 42 kDa proteases in five-day culture (most active also at pH 6) were inhibited by 1, 10- phenantroline in 2 mM concentration; the EDTA partially inhibited them at 8 mM concentration. All proteases were partially inhibited by 5 mM DTT in incubation buffers. On the other hand, the 2-mercaptoethanol in sample buffer did not alter the proteolytic activity. The inhibited 87 and 74 kDa proteases (by means of EDTA) can be reactivated by Ca2+ and partial by Fe2+ ions. The 40 kDa proteases in twoday culture can be reactivated by Zn2+ ions. No proteolytic activity was detected on the casein substrate gels.

Effects of exogenous chelators on phytoavailability and toxicity of Pb in Zinnia elegans Jacq.

Chelate-enhanced phytoremediation is considered as an effective method for the extraction of lead (Pb) by plants. However, more detailed studies are needed to evaluate the effect of exogenous chelators on phytoavailability and toxicity of Pb in plants, then to find out the proper applied concentration of chelators to minimize the combined toxicity to the plants and maximize phytoavailable Pb. To clarify these questions, the seed germination test of Zinnia elegans Jacq. exposed to solutions containing Pb and four types of chelators including sodium ethylenediamine tetra-acetic acid (Na 2EDTA), oxalic acid, tartaric acid and citric acid was observed. The results showed that the roots and shoots treated with equimolar chelators and Pb were longer than those treated with half and two folds of the molar concentrations of Pb. The growth of seedlings was inhibited by surplus addition of chelators, and the toxicity of complexes was less than that of Pb and chelators. In particular, 2.4 mM EDTA and 1.2 mM oxalic acid significantly ( P < 0.05) increased Pb uptake when the seeds were treated with 2.4 mM Pb. In the 4.8 mM Pb solution, Pb accumulation in the seedlings was markedly ( P < 0.05) increased by 4.8 mM EDTA, 2.4 mM tartaric acid, 4.8 mM tartaric acid and 2.4 mM citric acid, and amounted to 6752.4, 6453.8, 6541.4 and 6598.3 μg g −1, respectively. With the superfluous addition of chelators, Pb accumulation in the seedlings decreased in a concentration-dependent manner. When Pb was used at 2.4 mM, an equimolar concentration of EDTA not only increased Pb uptake but also stimulated the seedling growth. Thus, chelating agents in their appropriately concentrations could counteract Pb toxicity, but superfluous chelators resulted in less Pb uptake and growth inhibition of the seedlings.

Cytoprotective Effect of ICL670 (Deferasirox) on At20 Endocrine Cells Susceptible to Iron-Evoked Oxidative Damage.

A major cause of biological damage associated with tissue iron accumulation is the cellular acquisition of circulating labile plasma iron (LPI) by endocytic mechanisms and ensuing metal-catalyzed oxidations. Endocrine cells are presumed to have endocytic abilities and/or high susceptibility to the formation of reactive oxygen intermediates (ROIs), particularly those generated in the presence of labile iron. As these properties might be implicated in the early onset of endocrine dysfunctions observed in transfusional hemosiderosis, a major goal of iron chelation therapy is to prevent iron ingress into endocrine cells and ensuing toxicity and/or removal of cell-accumulated iron. Such properties of chelators have been afforded in cardiac cells (Glickstein et al. 2006, Blood In press) by treating LPI-carrying plasma with pharmacologically attainable concentrations of orally active iron chelators in clinical practice. The latter also evoked neutralization of metal-catalyzed ROS formation, by iron chelation and extrusion from cells and thereby supported cardiac functional restoration. We explored here whether addition of ICL670 (deferasirox) could rescue acutely iron-overloaded At20 pituitary cells from iron-toxicity, using fluorescence-plate reader and microscopy-imaging for live monitoring of cell functions and assessing toxicity in terms of:cell integrity (calcein cell retention assay);metabolic activities (mitochondrial Alamar-Blue assay); andintracellular (ACTH) hormone levels. Our studies indicate that in cell culture conditions and at pharmacological chelator concentrations, ICL670 can preserve both At20 endocrine cell viability and functional properties that were compromised by iron-catalyzed formation of ROIs.

Cytotoxic effects of intra and extracellular zinc chelation on human breast cancer cells

Zinc is an essential trace element with cofactor functions in a large number of proteins of intermediary metabolism, hormone secretion pathways, immune defence mechanisms, and as a cofactor of transcription factors it is also involved in the control of gene expression. Our study demonstrates that the modulation of intra and extracellular zinc alone is sufficient to induce metabolic changes or even apoptosis in two model human breast cancer cell lines MCF-7 and MDA-MB468. Treatment of breast cancer cells with different concentrations of a cell membrane permeable zinc chelator, N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the membrane impermeable zinc chelator, diethylenetriaminepentacetic acid, (DTPA) resulted in a significant increase of cell death. Features of apoptosis, such as chromatin condensation and nuclear fragmentation accompanied the DTPA and TPEN-induced cell death. A significant increase in the activity of caspase-9 was observed in both cell lines; whereas, caspase-3 activity was only increased in MDA-MB468 cells since caspase-3 is not expressed in MCF-7 cells. Caspase-8 activation was negligible in both cell lines. Addition of Zn 2+ or Cu 2+ prevented DTPA and TPEN-induced cytotoxicity, indicating that both bivalent cations can be replaced functionally to a certain extent in our experimental system. Interestingly, addition of Ca 2+, or Mg 2+ had no effect. The antioxidant N-Acetyl– l-Cysteine inhibited the cytotoxic effect of DTPA and TPEN, indicating that oxidative stress is the likely mediator of Zn-deficiency-related cell death.

Iron chelators reduce chromosomal breaks in ataxia-telangiectasia cells

Ataxia-telangiectasia (A-T) is characterized by ataxia, genomic instability, and increased cancer incidence. Previously, iron chelator concentrations which suppressed normal cell colony formation increased A-T cell colony formation. Similarly, iron chelators preferentially increased A-T cell colony formation following peroxide exposure compared to normal cells. Last, A-T cells exhibited increased short-term sensitivity to labile iron exposure compared to normal cells, an event corrected by recombinant ATM (rATM) expression. Since chromosomal damage is important in A-T pathology and iron chelators exert beneficial effects on A-T cells, we hypothesized that iron chelators would reduce A-T cell chromosomal breaks. We treated A-T, normal, and A-T cells expressing rATM with labile iron, iron chelators, antioxidants, and t-butyl hydroperoxide, and examined chromosomal breaks and ATM activation. Additionally, the effect of ATM-deficiency on transferrin receptor (TfR) expression and TfR activity blockage in A-T and syngeneic A-T cells expressing rATM was examined. We report that (1) iron chelators and iron-free media reduce spontaneous and t-butyl hydroperoxide-induced chromosomal breaks in A-T, but not normal, or A-T cells expressing rATM; (2) labile iron exposure induces A-T cell chromosomal breaks, an event lessened with rATM expression; (3) desferal, labile iron, and copper activate ATM; (4) A-T cell TfR expression is lowered with rATM expression and (5) blocking TfR activity with anti-TfR antibodies increases A-T cell colony formation, while lowering chromosomal breaks. ATM therefore functions in iron responses and the maintenance of genomic stability following labile iron exposure.

Deferiprone iron chelation as a novel therapy for experimental mucormycosis

Patients treated with the iron chelator deferoxamine are known to be more susceptible to mucormycosis. However, while deferoxamine is an iron chelator from the perspective of the human host, deferoxamine actually serves as a siderophore, delivering free iron to Rhizopus oryzae, the major cause of mucormycosis. Other iron chelators, including deferiprone, which do not deliver iron to R. oryzae have been described. We therefore sought to determine whether iron-chelation therapy with deferiprone would effectively treat mucormycosis. In vitro MIC and minimum fungicidal concentration (MFC) of the iron chelator, deferiprone, for R. oryzae were determined by microdilution assay. In addition, we compared the efficacy of deferiprone with that of liposomal amphotericin B (LAmB) in treating mucormycosis in diabetic ketoacidotic mice. Deferiprone demonstrated static activity against R. oryzae at 24 h, but showed cidality at 48 h of incubation. Deferiprone was as effective as LAmB at improving survival and decreasing brain fungal burden, and both drugs were more effective than placebo in non-iron-overloaded animals. Administration of free iron with deferiprone reversed protection, confirming that the mechanism of protection was iron chelation. Iron chelation is a promising, novel therapeutic strategy for refractory mucormycosis infections. Further studies are warranted to evaluate combination antifungal/iron chelation therapy and to evaluate the efficacy of other iron-chelating agents.