Disparate roles of zinc in chemical hypoxia-induced neuronal death

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Sujeong eKim

2015-01-01

Full Text Available Accumulating evidence has provided a causative role of zinc (Zn2+ in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2, deferoxamine (3 mM DFX, and sodium azide (2 mM NaN3, we evaluated whether Zn2+ is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn2+ release/accumulation in viable neurons. The immediate addition of the Zn2+ chelator, CaEDTA or N,N,N’N’-tetrakis-(2-pyridylmethyl ethylenediamine (TPEN, prevented the intracellular Zn2+ load and CoCl2-induced neuronal death, but neither 3-hour-later Zn2+ chelation nor a non-Zn2+ chelator ZnEDTA (1 mM demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn2+ rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn2+ release/accumulation is common during chemical hypoxia, Zn2+ might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

Disparate roles of zinc in chemical hypoxia-induced neuronal death.

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Kim, Sujeong; Seo, Jung-Woo; Oh, Shin Bi; Kim, So Hee; Kim, Inki; Suh, Nayoung; Lee, Joo-Yong

2015-01-01

Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

Chelatable trace zinc causes low, irreproducible KDAC8 activity.

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Toro, Tasha B; Edenfield, Samantha A; Hylton, Brandon J; Watt, Terry J

2018-01-01

Acetylation is an important regulatory mechanism in cells, and emphasis is being placed on identifying substrates and small molecule modulators of this post-translational modification. However, the reported in vitro activity of the lysine deacetylase KDAC8 is inconsistent across experimental setups, even with the same substrate, complicating progress in the field. We detected trace levels of zinc, a known inhibitor of KDAC8 when present in excess, even in high-quality buffer reagents, at concentrations that are sufficient to significantly inhibit the enzyme under common reaction conditions. We hypothesized that trace zinc in solution could account for the observed variability in KDAC8 activity. We demonstrate that addition of chelators, including BSA, EDTA, and citrate, and/or the use of a phosphate-based buffer instead of the more common tris-based buffer, eliminates the inhibition from low levels of zinc as well as the dependence of specific activity on enzyme concentration. This results in high KDAC8 activity that is consistent across buffer systems, even using low concentrations of enzyme. We report conditions that are suitable for several assays to increase both enzyme activity and reproducibility. Our results have significant implications for approaches used to identify substrates and small molecule modulators of KDAC8 and interpretation of existing data. Copyright © 2017 Elsevier Inc. All rights reserved.

Fluorescent zinc sensor with minimized proton-induced interferences: photophysical mechanism for fluorescence turn-on response and detection of endogenous free zinc ions.

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Kwon, Ji Eon; Lee, Sumin; You, Youngmin; Baek, Kyung-Hwa; Ohkubo, Kei; Cho, Jaeheung; Fukuzumi, Shunichi; Shin, Injae; Park, Soo Young; Nam, Wonwoo

2012-08-20

A new fluorescent zinc sensor (HNBO-DPA) consisting of 2-(2'-hydroxy-3'-naphthyl)benzoxazole (HNBO) chromophore and a di(2-picolyl)amine (DPA) metal chelator has been prepared and examined for zinc bioimaging. The probe exhibits zinc-induced fluorescence turn-on without any spectral shifts. Its crystal structure reveals that HNBO-DPA binds a zinc ion in a pentacoordinative fashion through the DPA and HNBO moieties. Steady-state photophysical studies establish zinc-induced deprotonation of the HNBO group. Nanosecond and femtosecond laser flash photolysis and electrochemical measurements provide evidence for zinc-induced modulation of photoinduced electron transfer (PeT) from DPA to HNBO. Thus, the zinc-responsive fluorescence turn-on is attributed to suppression of PeT exerted by deprotonation of HNBO and occupation of the electron pair of DPA, a conclusion that is further supported by density functional theory and time-dependent density functional theory (DFT/TD-DFT) calculations. Under physiological conditions (pH 7.0), the probe displays a 44-fold fluorescence turn-on in response to zinc ions with a K(d) value of 12 pM. The fluorescent response of the probe to zinc ions is conserved over a broad pH range with its excellent selectivity for zinc ions among biologically relevant metal ions. In particular, its sensing ability is not altered by divalent transition metal ions such as Fe(II), Cu(II), Cd(II), and Hg(II). Cell experiments using HNBO-DPA show its suitability for monitoring intracellular zinc ions. We have also demonstrated applicability of the probe to visualize intact zinc ions released from cells that undergo apoptosis. More interestingly, zinc-rich pools in zebrafish embryos are traced with HNBO-DPA during early developmental stages. The results obtained from the in vitro and in vivo imaging studies demonstrate the practical usefulness of the probe to detect zinc ions.

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

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Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

2014-01-15

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

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Sun, Xi; Zhou, Xixi; Du, Libo; Liu, Wenlan; Liu, Yang; Hudson, Laurie G.; Liu, Ke Jian

2014-01-01

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

Different roles of glutathione in copper and zinc chelation in Brassica napus roots.

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Zlobin, Ilya E; Kartashov, Alexander V; Shpakovski, George V

2017-09-01

We investigated the specific features of copper and zinc excess action on the roots of canola (Brassica napus L.) plants. Copper rapidly accumulated in canola root cells and reached saturation during several hours of treatment, whereas the root zinc content increased relatively slowly. Excessive copper and zinc entry inside the cell resulted in significant cell damage, as evidenced by alterations in plasmalemma permeability and decreases in cellular enzymatic activity. Zinc excess specifically damaged root hair cells, which correlated with a pronounced elevation of their labile zinc level. In vitro, we showed that reduced glutathione (GSH) readily reacted with copper ions to form complexes with blocked sulfhydryl groups. In contrast, zinc ions were ineffective as glutathione blockers, and glutathione molecules did not lose their specific chemical activity in the presence of Zn 2+ ions. The effect of copper and zinc excess on the glutathione pool in canola root cells was analysed by a combination of biochemical determination of total and oxidized glutathione contents and fluorescent staining of free reduced glutathione with monochlorobimane dye. Excess copper led to dose-dependent diminution of free reduced glutathione contents in the root cells, which could not be explained by the loss of total cellular glutathione or its oxidation. In contrast, we observed little effect of much higher intracellular zinc concentrations on the free reduced glutathione content. We concluded that GSH plays an important role in copper excess, but not zinc excess chelation, in canola root cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of feed supplementation with zinc chelate and zinc sulphate on selected humoral and cell-mediated immune parameters and cytokine concentration in broiler chickens.

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Jarosz, Łukasz; Marek, Agnieszka; Grądzki, Zbigniew; Kwiecień, Małgorzata; Kalinowski, Marcin

2017-06-01

The ability of poultry to withstand infectious disease caused by bacteria, viruses or protozoa depends upon the integrity of the immune system. Zinc is important for proper functioning of heterophils, mononuclear phagocytes and T lymphocytes. Numerous data indicate that the demand for zinc in poultry is not met in Poland due to its low content in feeds of vegetable origin. The aim of the study was to determine the effect of supplementation of inorganic (ZnSO 4 and ZnSO 4 + phytase enzyme), and organic forms of zinc (Zn with glycine and Zn with glycine and phytase enzyme) on selected parameters of the cellular and humoral immune response in broiler chickens by evaluating the percentage of CD3 + CD4 + , CD3 + CD8 + , CD25 + , MHC Class II, and BU-1 + lymphocytes, the phagocytic activity of monocytes and heterophils, and the concentration of IL-2, IL-10 and TNF-α in the peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. Phagocytic activity in whole blood was performed using the commercial Phagotest kit (ORPEGEN-Pharma, Immuniq, Poland). The results showed that supplementation with zinc chelates causes activation of the cellular and humoral immune response in poultry, helping to maintain the balance between the Th1 and Th2 response and enhancing resistance to infections. In contrast with chelates, the use of zinc in the form of sulphates has no immunomodulatory effect and may contribute to the development of local inflammatory processes in the digestive tract, increasing susceptibility to infection. Copyright © 2016. Published by Elsevier Ltd.

Effect of Extracellular Zinc Chelator on Rat Retinal Ganglion Cell Number, and Taurine and Zinc Transporters in These Cells

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Asarí Márquez García

2017-05-01

Full Text Available Zinc deficiency in humans causes decreased antioxidants in the retina and is related with abnormal darkness adaptation, cataracts, blindness, and macular degeneration. There is little information about the effects of zinc on the taurine system in mammalian retinal cells. Therefore, we studied the effect of zinc on the taurine transporter (TAUT and zinc transporters (ZnT-1 and 3 using the extracellular zinc chelator, diethylenetriaminepentaacetic acid (DTPA by fluorescence immunocytochemistry and immunohistochemistry in the ganglion cells (CG and cell layers of the retina of rats. Three days after administration of DTPA (10µM primary antibodies and secondary antibodies conjugated with rhodamine or fluorescein isothiocyanate (FITC were used as required. For immunocytochemical labeling approximately three hundred cells per condition were counted. For immunohistochemical labeling, the fluorescence intensity was measured as integrated optical density (DOI in four areas for each layer of tissue. DTPA produced a decrease of 32 % and 29 % in GC of the total cells labeled with antibody against glycoprotein Thy 1.1 and γ-synuclein, respectively. It also produced a significant decrease in TAUT localization in 27 and 28 % compared to controls. DTPA produced a decrease in the localization of ZnT-1 and ZnT-3 in the retina layers (ganglion cells, GCC and the outer and inner plexiform, CEP and CIP. The study of these molecules in the retina is relevant to understanding the interactions of taurine and zinc in this structure.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

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Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2013-04-15

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

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Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

2013-01-01

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ m ). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

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Tsung-I Chen

Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

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Chen, Michael Yu-Chih

2016-01-01

In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

The relative efficiency of zinc carriers on growth and zinc nutrition of corn

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Prasad, B.; Sinha, K.

1981-01-01

A comparison of different zinc carriers showed that application of Zn-DTPA, Zn-EDTA, Zn-fulvate and ZnSO 4 significantly increased the dry matter yield and zinc uptake by corn over the control treatment where no zinc was applied. The chelates in particular enhanced to a greater extent the uptake of both native and applied sources than that observed with ZnSO 4 as the zinc carrier. Both the dry matter yield and zinc uptake by corn showed a positive and significant relationship with self-diffusion coefficient of zinc showing thereby that diffusion contributed mainly the supply of Zn from the ambient soil matrix to plant roots. The effectiveness of the chelates varied depending on their capacity to retain Zn in a soluble form in the soil solution. It is evident that zinc nutrition of plants in alkaline and calcareous soils can be more effectively regulated by both synthetic and natural chelates or organic manures which contain substantial amount of complexed zinc. (orig.)

Depletion of intracellular zinc from neurons by use of an extracellular chelator in vivo and in vitro.

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Frederickson, Christopher J; Suh, Sang W; Koh, Jae-Young; Cha, Yoo K; Thompson, Richard B; LaBuda, Christopher J; Balaji, Rengarajan V; Cuajungco, Math P

2002-12-01

The membrane-impermeable chelator CaEDTA was introduced extracellularly among neurons in vivo and in vitro for the purpose of chelating extracellular Zn(2+). Unexpectedly, this treatment caused histochemically reactive Zn(2+) in intracellular compartments to drop rapidly. The same general result was seen with intravesicular Zn(2+), which fell after CaEDTA infusion into the lateral ventricle of the brain, with perikaryal Zn(2+) in Purkinje neurons (in vivo) and with cortical neurons (in vitro). These findings suggest either that the volume of zinc ion efflux and reuptake is higher than previously suspected or that EDTA can enter cells and vesicles. Caution is therefore warranted in attempting to manipulate extracellular or intracellular Zn(2+) selectively.

Effects of Dietary Zinc Pectin Oligosaccharides Chelate Supplementation on Growth Performance, Nutrient Digestibility and Tissue Zinc Concentrations of Broilers.

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Wang, Zhongcheng; Yu, Huimin; Wu, Xuezhuang; Zhang, Tietao; Cui, Hu; Wan, Chunmeng; Gao, Xiuhua

2016-10-01

The experiment was conducted to investigate the effects of zinc pectin oligosaccharides (Zn-POS) chelate on growth performance, nutrient digestibility, and tissue zinc concentrations of Arbor Acre broilers aged from 1 to 42 days. A total of 576 1-day-old broilers were randomly assigned into 4 groups with 9 replicates per group and 16 chicks per replicate. Chicks were fed either a basal diet (control) or basal diet supplemented with Zn-POS at 300 (Zn-POS-300), 600 (Zn-POS-600), or 900 mg/kg (Zn-POS-900), respectively, for 42 days. A 3-day metabolism trial was conducted during the last week of the experiment feeding. The average daily gain and the average daily feed intake of Zn-POS-600 were significantly higher (P digestibility of dry matter, crude protein, and metabolic energy among all groups. The control group had the lowest apparent digestibility of dry matter (P digestibility of dry matter in Zn-POS-600 was higher (P digestibility of crude protein in Zn-POS-600 or Zn-POS-900 was higher (P digestibility of metabolic energy in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) than that of Zn-POS-300. Zn-POS-600 had the highest liver zinc concentrations (P < 0.05), while Zn-POS-900 had the highest pancreatic zinc concentrations (P < 0.05). Our data suggest that the supplementation of 600 mg/kg Zn-POS is optimal in improving the average daily gain and the average daily feed intake, utilization of dietary dry matter and crude protein, and increasing tissue zinc concentrations in liver and pancreas of broilers.

Influence of extracellular zinc on M1 microglial activation.

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Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

2017-02-27

Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

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Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

2008-10-01

The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

Neurotoxicity of dental amalgam is mediated by zinc.

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Lobner, D; Asrari, M

2003-03-01

The use of dental amalgam is controversial largely because it contains mercury. We tested whether amalgam caused toxicity in neuronal cultures and whether that toxicity was caused by mercury. In this study, we used cortical cell cultures to show for the first time that amalgam causes nerve cell toxicity in culture. However, the toxicity was not blocked by the mercury chelator, 2,3-dimercaptopropane-1-sulphonate (DMPS), but was blocked by the metal chelator, calcium disodium ethylenediaminetetraacetate (CaEDTA). DMPS was an effective mercury chelator in this system, since it blocked mercury toxicity. Of the components that comprise amalgam (mercury, zinc, tin, copper, and silver), only zinc neurotoxicity was blocked by CaEDTA. These results indicate that amalgam is toxic to nerve cells in culture by releasing zinc. While zinc is known to be neurotoxic, ingestion of zinc is not a major concern because zinc levels in the body are tightly regulated.

Chelator induced phytoextraction and in situ soil washing of Cu

International Nuclear Information System (INIS)

Kos, Bostjan; Lestan, Domen

2004-01-01

In a soil column experiment, we investigated the effect of 5 mmol kg -1 soil addition of citric acid, ethylenediamine tetraacetate (EDTA), diethylenetriamine-pentaacetate (DTPA) and [S,S]-stereoisomer of ethylenediamine-disuccinate (EDDS) on phytoextraction of Cu from a vineyard soil with 162.6 mg kg -1 Cu, into the test plant Brassica rapa var. pekinensis. We also examined the use of a horizontal permeable barrier, composed of layers of nutrient enriched sawdust and apatite, for reduction of chelator induced Cu leaching. The addition of all chelators, except citric acid, enhanced Cu mobility and caused leaching of 19.5-23% of initial total Cu from the soil column. However, Cu plant uptake did not increase accordingly; the most effective was the EDDS treatment, in which plant Cu concentration reached 37.8±1.3 mg kg -1 Cu and increased by 3.3-times over the control treatment. The addition of none of the chelators in the concentration range from 5 to 15 mmol kg -1 exerted any toxic effect on respiratory soil microorganisms. When EDDS was applied into the columns with horizontal permeable barriers, only 0.53±0.32% of the initial total Cu was leached. Cu (36.7%) was washed from the 18 cm soil layer above the barrier and accumulated in the barrier. Our results indicate that rather than for a reduction of Cu leaching during rather ineffective chelate induced Cu phytoextraction, horizontal permeable barriers could be more effective in a new remediation technique of controlled in situ soil washing of Cu with biodegradable chelates

Zinc regulates Nox1 expression through a NF-κB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells.

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Salazar, G; Huang, J; Feresin, R G; Zhao, Y; Griendling, K K

2017-07-01

The role of oxidative stress and inflammation in the development and progression of cardiovascular diseases (CVD) is well established. Increases in oxidative stress can further exacerbate the inflammatory response and lead to cellular senescence. We previously reported that angiotensin II (Ang II) and zinc increase reactive oxygen species (ROS) and cause senescence of vascular smooth muscle cells (VSMCs) and that senescence induced by Ang II is a zinc-dependent process. Zinc stimulated NADPH oxidase (Nox) activity; however, the role of Nox isoforms in zinc effects was not determined. Here, we show that downregulation of Nox1, but not Nox4, by siRNA prevented both Ang II- and zinc-induced senescence in VSMCs. On the other hand, overexpression of Nox1 induced senescence, which was associated with reduced proliferation, reduced expression of telomerase and increased DNA damage. Zinc increased Nox1 protein expression, which was inhibited by chelation of zinc with TPEN and by overexpression of the zinc exporters ZnT3 and ZnT10. These transporters work to reduce cytosolic zinc, suggesting that increased cytosolic zinc mediates Nox1 upregulation. Other metals including copper, iron, cobalt and manganese failed to upregulate Nox1, suggesting that this pathway is zinc specific. Nox1 upregulation was inhibited by actinomycin D (ACD), an inhibitor of transcription, by inhibition of NF-κB, a known Nox1 transcriptional regulator and by N-acetyl cysteine (NAC) and MitoTEMPO, suggesting that NF-κB and mitochondrial ROS mediate zinc effects. Supporting this idea, we found that zinc increased NF-κB activation in the cytosol, stimulated the translocation of the p65 subunit to the nucleus, and that zinc accumulated in mitochondria increasing mitochondrial ROS, measured using MitoSox. Further, zinc-induced senescence was reduced by inhibition of NF-κB or reduction of mitochondrial ROS with MitoTEMPO. NF-κB activity was also reduced by MitoTEMPO, suggesting that mitochondrial ROS

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

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Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

2009-01-01

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

The lack of effects of zinc and nitric oxide in initial state of pilocarpine-induced seizures.

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Noyan, Behzat; Jensen, Morten Skovgaard; Danscher, Gorm

2007-07-01

In this study we investigated whether intracerebroventricular (i.c.v.) injection of L-NAME (a nitric oxide synthase inhibitor) or CaEDTA (an extracellular zinc chelator) or the combination of the two could affect the initial phase of pilocarpine induced (2 h) seizures. Two groups of rats were used. Animals from both groups were given with i.c.v. injections of either saline (10 microl), L-NAME (150 microg/10 microl), CaEDTA (100 mM/10 microl) or L-NAME and CaEDTA. One group received pilocarpine HCl (380 mg/kg i.p.) the other served as control. Pilocarpine HCl was injected intraperitoneally 10 min later. The behavior of the animals was observed for 2h and the intensity of their seizures was scored. The rats were then sacrificed and their brains were removed and analyzed for zinc ions by using the immersion autometallography and the TSQ fluorescence staining. All the animals which received pilocarpine HCl developed seizures. Despite treatment with L-NAME and/or CaEDTA we found that the latency and the intensity of seizures were similar in both groups investigated. The distribution of stainable zinc ions and the intensity of staining in hippocampus were not affected by pilocarpine and found unchanged after L-NAME and/or CaEDTA injections in both the control animals and the pilocarpine treated animals. The data suggest that the nitric oxide system and zinc ions do not affect pilocarpine-induced seizures in their initial state.

Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity.

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Yui, Satoru; Nakatani, Yuichi; Hunter, Michael J; Chazin, Walter J; Yamazaki, Masatoshi

2002-06-01

Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner. The present study was undertaken to elucidate which subunit is responsible for the apoptosis-inducing activity, and to explore the mechanism of zinc-reversible apoptosis induction. The apoptosis-inducing activity of recombinant human MRP8 (rhMRP8) and recombinant human MRP14 (rhMRP14) was examined against EL-4 lymphoma cells in vitro. To determine whether zinc deprivation by calprotectin was essential for the cytotoxicity, the activity of calprotectin was tested under conditions where physical contact between the factor and the cells was precluded by a low molecular weight cut-off dialysis membrane. The cytotoxicity of rhMRP14 against EL-4 cells was first detected at 10 microM in a standard medium, whereas rhMRP8 caused only marginal cytotoxicity at 40 microM. A mixture of both proteins showed higher specific activity (onset of cytotoxicity at 5 microM). When the cells were cultured in divalent cation-depleted medium, each dose-response curve was shifted to about a four-fold lower concentration range. Calprotectin was found to induce cell death even when the complex and the target cells were separated by dialysis membrane. A membrane-impermeable zinc chelator, diethylenetriamine pentaacetic acid (DTPA), also induced target cell apoptosis in a similar time-course as calprotectin. Moreover, the activities of calprotectin and DTPA were completely inhibited by the presence of zinc ions. These data indicate that calprotectin has higher specific activity to induce apoptosis than the Individual subunits, and that the mechanism is exclusion of zinc

A comparative study on zinc fertilizer brands available in the markets of Jessore region

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GMM Islam

2017-12-01

Full Text Available A study was conducted in Monirampur upazila under Jessore district from July to December, 2016 to collect information on names, numbers and comparative availability of different brands of Zinc fertilizers in order to aid the assessment of nutrient status for quality of the brands. For this purpose, information was collected from 54 randomly selected fertilizer shops (20 BCIC fertilizer dealers and 34 retailers through questionnaire interview. In the study total 77 brands [41 Zinc sulfate (mono, 11 Zinc sulfate (hepta and 25 Chelated zinc] of zinc fertilizer marketed by 49 companies were found in the upazila. Zingsul, Mim zinc, Grogin, Bumper mono zinc, Eon zinc and Geel mono of Zinc sulfate (mono brands, Topaz of Zinc sulfate (hepta brands and Mim zinc gold of Chelated zinc brands were mostly available. “Grogin” of Zinc sulfate (mono and “Topaz” of Zinc sulfate (hepta were the top most available. Ten percent of Zinc sulfate (hepta mentioned no registration number. There was a significant difference between highest and lowest MRP of all types (imported, supplied and manufactured of Zinc sulfate (mono and Zinc sulfate (hepta fertilizer as well as imported Chelated zinc brands.

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

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Yang C

2017-02-01

Full Text Available Chunguang Yang,1,* Xueyou Ma,1,* Zhihua Wang,1 Xing Zeng,1 Zhiquan Hu,1 Zhangqun Ye,1 Guanxin Shen2 1Department of Urology, Tongji Hospital, 2Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work 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

Involvement of amygdalar extracellular zinc in rat behavior for passive avoidance.

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Takeda, Atsushi; Minami, Akira; Yamaide, Rie; Oku, Naoto

2004-03-25

On the basis of the evidence that zinc is released from glutamatergic neuron terminals in the amygdala, the effect of chelation of amygdalar extracellular zinc on glutamate release from the neuron terminals was studied by using in vivo microdialysis. When the amygdala was perfused with 100 microM CaEDTA to chelate extracellular zinc, glutamate concentration in the perfusate was decreased significantly, whereas that tended to be increased by perfusion with 100 microM ZnEDTA as a control. The effect of CaEDTA on extracellular glutamate levels was different between the amygdala and hippocampus, implying that modulation of glutamate signaling by zinc is different between them. To evaluate chelation of zinc in rat behavior, perfusion of the amygdala with CaEDTA was started 40 min before behavioral test for passive avoidance. The behavior for passive avoidance was impaired during perfusion with CaEDTA. On the other hand, the behavior during perfusion with ZnEDTA was more rapidly developed than that with vehicle only. These results suggest that amygdalar extracellular zinc is involved in the behavior for passive avoidance.

Chelation: Harnessing and Enhancing Heavy Metal Detoxification—A Review

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Margaret E. Sears

2013-01-01

Full Text Available Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease.

Immersion autometallography: histochemical in situ capturing of zinc ions in catalytic zinc-sulfur nanocrystals.

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Danscher, Gorm; Stoltenberg, Meredin; Bruhn, Mikkel; Søndergaard, Chris; Jensen, Dorete

2004-12-01

In the mid-1980s, two versions of Timm's original immersion sulfide silver method were published. The authors used immersion of tissue in a sulfide solution as opposed to Timm, who used immersion of tissue blocks in hydrogen sulfide-bubbled alcohol. The autometallography staining resulting from the "sulfide only immersion" was not particularly impressive, but the significance of this return to an old approach became obvious when Wenzel and co-workers presented their approach in connection with introduction by the Palmiter group of zinc transporter 3 (ZnT3). The Wenzel/Palmiter pictures are the first high-resolution, high-quality pictures taken from tissues in which free and loosely bound zinc ions have been captured in zinc-sulfur nanocrystals by immersion. The trick was to place formalin-fixed blocks of mouse brains in a solution containing 3% glutaraldehyde and 0.1% sodium sulfide, ingredients used for transcardial perfusion in the zinc-specific NeoTimm method. That the NeoTimm technique results in silver enhancement of zinc-sulfur nanocrystals has been proved by proton-induced X-ray multielement analyses (PIXE) and in vivo chelation with diethyldithiocarbamate (DEDTC). The aims of the present study were (a) to make the immersion-based capturing of zinc ions in zinc-sulfur nanocrystals work directly on sections and slices of fixed brain tissue, (b) to work out protocols that ensure zinc specificity and optimal quality of the staining, (c) to apply "immersion autometallography" (iZnSAMG) to other tissues that contain zinc-enriched (ZEN) cells, and (d) to make the immersion approach work on unfixed fresh tissue.

Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity.

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Nakatani, Yuichi; Yamazaki, Masatoshi; Chazin, Walter J; Yui, Satoru

2005-10-24

S100A8/A9 (calprotectin), which is released by neutrophils under inflammatory conditions, has the capacity to induce apoptosis in various cells. We previously reported that S100A8/A9 induces apoptosis of EL-4 lymphoma cells via the uptake of extracellular zinc in a manner similar to DTPA, a membrane-impermeable zinc chelator. In this study, S100A8/A9-induced apoptosis was examined in several cell lines that are weakly sensitive to DTPA, suggesting S100A8/A9 is directly responsible for apoptosis in these cells. Since zinc inhibits apoptosis of MM46, one of these cells, the regulation by zinc of the capacity of S100A8/A9 to bind MM46 cells was studied. When MM46 cells were incubated with S100A8/A9 in standard or zinc-depleted medium, the amounts of S100A8/A9 bound to cells was markedly lower at 3 h than at 1 h. In contrast, when MM46 cells were incubated with S100A8/A9 in the presence of high levels of zinc, binding to cells was the same at 1 and 3 h. When the cells were permeabilized with saponin prior to analysis, a larger amount of cell-associated S100A8/A9 was detected at 3 h. The amount was further increased in cells treated with chloroquine, suggesting that S100A8/A9 was internalized and degraded in lysosomes. Although it has been reported that S100A8/A9 binds to heparan sulfate on cell membranes, the amount of S100A8/A9 bound to MM46 cells was not reduced by heparinase treatment, but was reduced by trypsin treatment. These results suggest that S100A8/A9 induces apoptosis by direct binding to MM46 cells, and that this activity is regulated by zinc.

Rising intracellular zinc by membrane depolarization and glucose in insulin-secreting clonal HIT-T15 beta cells.

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Slepchenko, Kira G; Li, Yang V

2012-01-01

Zinc (Zn(2+)) appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30-60 mM) was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM) induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.

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Lee, Joo-Yong; Hwang, Jung Jin; Park, Mi-Ha; Koh, Jae-Young

2006-01-01

Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague-Dawley rat brains were double-stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage-specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc-specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.

Matrix separation by chelation to prepare biological materials for isotopic zinc analysis by inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Durrant, S.F.; Krushevska, A.; Amarasiriwardena, D.; Argentine, M.D.; Romon-Guesnier, S.; Barnes, R.M.

1994-01-01

Following an evaluation of three chelating resins [Chelex-100, poly(dithiocarbamate) (PDTC) and carboxymethylated poly(ethyleneimine)-poly(methylenepolyphenylene) isocyanate (CPPI)], a procedure was established with the last of these for the separation of Zn from biological matrix elements prior to 70 Zn: 68 Zn isotopic analysis by inductively coupled plasma mass spectrometry (ICP-MS). The method was verified by establishing Zn recoveries and by determining its effectiveness in removing Cl and Na from buffered test solutions. Calcium, Na, and Zn concentration data were determined by inductively coupled plasma atomic emission spectrometry. Chlorine was measured by electrothermal vaporization ICP-MS. The efficacy of the technique was demonstrated by the determination of zinc isotope ratios in bovine milk and human urine. (Author)

ZINC-INDUCED HYPERLEPTINEMIA IN RATS RELATED TO THE AMELIORATION OF SUCROSE-INDUCED OBESITY WITH ZINC REPLETION

International Nuclear Information System (INIS)

HEIBASHY, M.I.; EL-NAHLA, A.M.; ASHOUR, I.; SALEH, SH.Y.A.

2008-01-01

Thirty adult albino rats (Rattus rattus) at 6 weeks of age were divided into three groups (ten for each). The first group was fed a standard laboratory diet for 8 weeks (control). The second group was made obese by giving them 32% sucrose solution in addition to the standard laboratory diet .The third group was received zinc supplementation (50 mg zinc acetate/ litre) with their sucrose solution. Body weight of all rats was measured weekly for 8 weeks. At 14 weeks of age, rats were killed and fasting blood samples were obtained. Serum glucose, insulin, cholesterol, triglyceride, leptin, tumour necrosis factor-α and zinc were measured.Results showed remarkable changes in body weights in sucrose fed rats only when compared to control and supplemented zinc rats group. Serum glucose, insulin, cholesterol and triglycerides were significantly increased in sucrose fed rats than both control and sucrose with zinc group. Serum leptin showed significant increase in sucrose fed rats than control and also showed higher significant value in sucrose fed rats supplemented with zinc comparing with sucrose fed rats and control ones. Tumour necrosis factor-? did not show any significant difference between all groups. Serum zinc concentration was decreased significantly in sucrose fed rats as compared to control. On the other hand, it was increased significantly in sucrose fed rats supplemented with zinc than other both groups. It could be concluded that zinc supplementation induced hyperleptinemia caused ameliorating effects in obese rats

Effect of inorganic and organic zinc supplementation on coccidial infections in goat kids

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Petra Strnadová

2011-01-01

Full Text Available The aim of this study was to identify the effect of zinc-enriched diet fed to goats and their kids on the number of Coccidia oocysts shed by kids, on clinical signs of coccidiosis, weight gains, and kids’ blood plasma concentration of zinc. A total of 22 goat kids were divided into 4 groups of 5 or 6 animals. Goats and kids from the control group did not receive any additional zinc, the second group was supplemented with inorganic zinc (zinc oxide, the third group was given zinc lactate, and the fourth group received chelated zinc. Samples of kids’ faeces were taken weekly from 3 to 9 weeks of their age (a total of 7 samples were taken. Samples of faeces were examined by a quantitative method to detect the number of oocysts. Kids were weighed weekly and their blood was taken in order to determine zinc concentrations in blood plasma. Animals from the group supplemented with zinc chelate and zinc lactate shed a significantly (p ≤ 0.05 lower number of oocysts (13.4% and 11.9%, respectively compared to the number of oocyst shed by control and zinc oxide supplemented groups (25% and 49.7%, respectively. Shedding of oocysts was not accompanied by clinical symptoms of coccidiosis in any of the groups. Kids supplemented with zinc chelate showed significantly highest weight gains and blood plasma concentration of zinc (p ≤ 0.05 as compared to control and inorganic zinc supplemented groups. Organic zinc is to be recommended to be used as a prophylaxis against coccidiosis in goat kids.

Zinc movement in the brain under kainate-induced seizures.

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Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

2003-05-01

On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

Rising Intracellular Zinc by Membrane Depolarization and Glucose in Insulin-Secreting Clonal HIT-T15 Beta Cells

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Kira G. Slepchenko

2012-01-01

Full Text Available Zinc (Zn2+ appears to be intimately involved in insulin metabolism since insulin secretion is correlated with zinc secretion in response to glucose stimulation, but little is known about the regulation of zinc homeostasis in pancreatic beta-cells. This study set out to identify the intracellular zinc transient by imaging free cytosolic zinc in HIT-T15 beta-cells with fluorescent zinc indicators. We observed that membrane depolarization by KCl (30–60 mM was able to induce a rapid increase in cytosolic concentration of zinc. Multiple zinc transients of similar magnitude were elicited during repeated stimulations. The amplitude of zinc responses was not affected by the removal of extracellular calcium or zinc. However, the half-time of the rising slope was significantly slower after removing extracellular zinc with zinc chelator CaEDTA, suggesting that extracellular zinc affect the initial rising phase of zinc response. Glucose (10 mM induced substantial and progressive increases in intracellular zinc concentration in a similar way as KCl, with variation in the onset and the duration of zinc mobilization. It is known that the depolarization of beta-cell membrane is coupled with the secretion of insulin. Rising intracellular zinc concentration may act as a critical signaling factor in insulin metabolism of pancreatic beta-cells.

Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD.

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Rhys Hamon

Full Text Available Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD, cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2

Zinc species distribution in EDTA-extract residues of zinc-contaminated soil

International Nuclear Information System (INIS)

Chang, S.-H.; Wei, Y.-L.; Wang, H. Paul

2007-01-01

Soil sample from a site heavily contaminated with >10 wt.% zinc is sampled and extracted with aqueous solutions of ethylene diamine tetra-acetic acid (EDTA) that is a reagent frequently used to extract heavy metals in soil remediation. Three liquid/soil ratios (5/1, 20/1, and 100/1) were used in the extracting experiment. The molecular environment of the residual Zn in the EDTA-extract residues of zinc-contaminated soil is investigated with XANES technique. The results indicate that EDTA does not show considerable preference of chelating for any particular Zn species during the extraction. Zn species distribution in the sampled soil is found to resemble that in all EDTA-extract residues; Zn(OH) 2 is determined as the major zinc species (60-70%), seconded by organic zinc (21-26%) and zinc oxide (9-14%)

Sequestration of zinc oxide by fimbrial designer chelators

DEFF Research Database (Denmark)

Kjærgaard, Kristian; Sørensen, Jack K; Schembri, Mark

2000-01-01

O. Sequences responsible for ZnO adherence were identified, and distinct binding motifs were characterized. The sequences selected exhibited various degrees of affinity and specificity towards ZnO. Competitive binding experiments revealed that the sequences recognized only the oxide form of Zn. Interestingly......, one of the inserts exhibited significant homology to a specific sequence in a putative zinc-containing helicase, which suggests that searches such as this one may aid in identifying binding motifs in nature. The zinc-binding bacteria might have a use in detoxification of metal-polluted water...

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc.

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Anderson, Charles T; Radford, Robert J; Zastrow, Melissa L; Zhang, Daniel Y; Apfel, Ulf-Peter; Lippard, Stephen J; Tzounopoulos, Thanos

2015-05-19

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling.

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc

Science.gov (United States)

Anderson, Charles T.; Radford, Robert J.; Zastrow, Melissa L.; Zhang, Daniel Y.; Apfel, Ulf-Peter; Lippard, Stephen J.; Tzounopoulos, Thanos

2015-01-01

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling. PMID:25947151

Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

International Nuclear Information System (INIS)

Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

1988-01-01

In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn 2+ , while Fe 2+ and Mn 2+ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca 2+ , phorbol ester, or antigen

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis

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Bo Young Choi

2017-09-01

Full Text Available Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS, such as matrix metallopeptidase 9 (MMP-9 activation, blood-brain barrier (BBB disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 (ZnT3 knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

Science.gov (United States)

Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

2017-09-28

Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

Science.gov (United States)

Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

2005-11-30

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

Fusaric acid induces a notochord malformation in zebrafish via copper chelation.

Science.gov (United States)

Yin, Emily S; Rakhmankulova, Malika; Kucera, Kaury; de Sena Filho, Jose Guedes; Portero, Carolina E; Narváez-Trujillo, Alexandra; Holley, Scott A; Strobel, Scott A

2015-08-01

Over a thousand extracts were tested for phenotypic effects in developing zebrafish embryos to identify bioactive molecules produced by endophytic fungi. One extract isolated from Fusarium sp., a widely distributed fungal genus found in soil and often associated with plants, induced an undulated notochord in developing zebrafish embryos. The active compound was isolated and identified as fusaric acid. Previous literature has shown this phenotype to be associated with copper chelation from the active site of lysyl oxidase, but the ability of fusaric acid to bind copper ions has not been well described. Isothermal titration calorimetry revealed that fusaric acid is a modest copper chelator with a binding constant of 4.4 × 10(5) M(-1). These results shed light on the toxicity of fusaric acid and the potential teratogenic effects of consuming plants infected with Fusarium sp.

Selective separation of indium by iminodiacetic acid chelating resin

International Nuclear Information System (INIS)

Fortes, M.C.B.; Benedetto, J.S.; Martins, A.H.

2007-01-01

- Indium can be recovered by treating residues, flue dusts, slags, and metallic intermediates in zinc smelting. This paper investigates the adsorption characteristics of indium and iron on an iminodiacetic acid chelating resin, Amberlite R IRC748 (Rohm and Haas Co.-USA). High concentrations of iron are always present in the aqueous feed solution of indium recovery. In addition, the chemical behaviour of iron in adsorptive systems is similar to that of indium. The metal concentrations in the aqueous solution were based on typical indium sulfate leach liquor obtained from zinc hydrometallurgical processing in a Brazilian plant. The ionic adsorption experiments were carried out by the continuous column method. Amberlite R IRC748 resin had a high affinity for indium under acidic conditions. Indium ions adsorbed onto the polymeric resin were eluted with a 0.5 mol/dm 3 sulphuric acid solution passed through the resin bed in the column. 99.5% pure indium sulfate aqueous solution was obtained using the iminodiacetic acid chelating resin Amberlite R IRC748. (author)

Modelling chelate-Induced phytoextraction: functional models predicting bioavailability of metals in soil, metal uptake and shoot biomass

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Pasqualina Sacco

2006-06-01

Full Text Available Chelate-induced phytoextraction of heavy metals from contaminated soils requires special care to determine, a priori, the best method of chelate application, in terms of both dose and timing. In fact, the chelate dose must assure the bioavailability of the metal to the plant without increasing leaching risk and giving toxic effects. Three mathematical models are here proposed for usefully interpreting the processes taking place: a increased soil bioavailability of metals by chelants; b metal uptake by plants; c variation in plant biomass. The models are implemented and validated using data from pot and lysimeter trials. Both the chelate dose and the time elapsed since its application affected metal bioavailability and plant response. Contrariwise, the distribution strategy (single vs. split application seems to produce significant differences both in plant growth and metal uptake, but not in soil metal bioavailability. The proposed models may help to understand and predict the chelate dose – effect relationship with less experimental work.

Modelling chelate-Induced phytoextraction: functional models predicting bioavailability of metals in soil, metal uptake and shoot biomass

Directory of Open Access Journals (Sweden)

Pasqualina Sacco

Full Text Available Chelate-induced phytoextraction of heavy metals from contaminated soils requires special care to determine, a priori, the best method of chelate application, in terms of both dose and timing. In fact, the chelate dose must assure the bioavailability of the metal to the plant without increasing leaching risk and giving toxic effects. Three mathematical models are here proposed for usefully interpreting the processes taking place: a increased soil bioavailability of metals by chelants; b metal uptake by plants; c variation in plant biomass. The models are implemented and validated using data from pot and lysimeter trials. Both the chelate dose and the time elapsed since its application affected metal bioavailability and plant response. Contrariwise, the distribution strategy (single vs. split application seems to produce significant differences both in plant growth and metal uptake, but not in soil metal bioavailability. The proposed models may help to understand and predict the chelate dose – effect relationship with less experimental work.

Zinc is released by cultured astrocytes as a gliotransmitter under hypoosmotic stress-loaded conditions and regulates microglial activity.

Science.gov (United States)

Segawa, Shohei; Nishiura, Takeshi; Furuta, Takahiro; Ohsato, Yuki; Tani, Misaki; Nishida, Kentaro; Nagasawa, Kazuki

2014-01-17

Astrocytes contribute to the maintenance of brain homeostasis via the release of gliotransmitters such as ATP and glutamate. Here we examined whether zinc was released from astrocytes under stress-loaded conditions, and was involved in the regulation of microglial activity as a gliotransmitter. Hypoosmotic stress was loaded to astrocytes using balanced salt solution prepared to 214-314 mOsmol/L, and then intra- and extra-cellular zinc levels were assessed using Newport Green DCF diacetate (NG) and ICP-MS, respectively. Microglial activation by the astrocytic supernatant was assessed by their morphological changes and poly(ADP-ribose) (PAR) polymer accumulation. Exposure of astrocytes to hypoosmotic buffer, increased the extracellular ATP level in osmolarity-dependent manners, indicating a load of hypoosmotic stress. In hypoosmotic stress-loaded astrocytes, there were apparent increases in the intra- and extra-cellular zinc levels. Incubation of microglia in the astrocytic conditioned medium transformed them into the activated "amoeboid" form and induced PAR formation. Administration of an extracellular zinc chelator, CaEDTA, to the astrocytic conditioned medium almost completely prevented the microglial activation. Treatment of astrocytes with an intracellular zinc chelator, TPEN, suppressed the hypoosmotic stress-increased intracellular, but not the extracellular, zinc level, and the increase in the intracellular zinc level was blocked partially by a nitric oxide synthase inhibitor, but not by CaEDTA, indicating that the mechanisms underlying the increases in the intra- and extra-cellular zinc levels might be different. These findings suggest that under hypoosmotic stress-loaded conditions, zinc is released from astrocytes and then plays a primary role in microglial activation as a gliotransmitter. Copyright © 2013 Elsevier Inc. All rights reserved.

Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

1988-05-15

In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn/sup 2 +/, while Fe/sup 2 +/ and Mn/sup 2 +/ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca/sup 2 +/, phorbol ester, or antigen.

Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells.

Science.gov (United States)

Daaboul, Doha; Rosenkranz, Eva; Uciechowski, Peter; Rink, Lothar

2012-10-01

Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.

Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

Energy Technology Data Exchange (ETDEWEB)

Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.; Kong, Betty Y.; Gleber, Sophie C.; Vogt, Stefan; Chen, Si; Garwin, Seth A.; Bayer, Amanda R.; Dravid, Vinayak P.; Woodruff, Teresa K.; O' Halloran, Thomas V.

2014-12-15

Fertilization of a mammalian egg initiates a series of 'zinc sparks' that are necessary to induce the egg-to-embryo transition. Despite the importance of these zinc-efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches that resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy-dispersive spectroscopy, X-ray fluorescence microscopy and three-dimensional elemental tomography for high-resolution elemental mapping. We show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 10(6) zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. The discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes

Zinc at glutamatergic synapses.

Science.gov (United States)

Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

2009-01-12

It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

Relative contribution of phytates, fibers, and tannins to low iron and zinc in vitro solubility in pearl millet (Pennisetum glaucum) flour and grain fractions.

Science.gov (United States)

Lestienne, Isabelle; Caporiccio, Bertrand; Besançon, Pierre; Rochette, Isabelle; Trèche, Serge

2005-10-19

In vitro digestions were performed on pearl millet flours with decreased phytate contents and on two dephytinized or nondephytinized pearl millet grain fractions, a decorticated fraction, and a bran fraction with low and high fiber and tannin contents, respectively. Insoluble residues of these digestions were then incubated with buffer or enzymatic solutions (xylanases and/or phytases), and the quantities of indigestible iron and zinc released by these different treatments were determined. In decorticated pearl millet grain, iron was chelated by phytates and by insoluble fibers, whereas zinc was almost exclusively chelated by phytates. In the bran of pearl millet grain, a high proportion of iron was chelated by iron-binding phenolic compounds, while the rest of iron as well as the majority of zinc were chelated in complexes between phytates and fibers. The low effect of phytase action on iron and zinc solubility of bran of pearl millet grain shows that, in the case of high fiber and tannin contents, the chelating effect of these compounds was higher than that of phytates.

Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes.

Science.gov (United States)

Csermely, P; Szamel, M; Resch, K; Somogyi, J

1988-05-15

In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested (Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D., and Ullrich, A. (1986) Science 233, 853-859). In the present report, we demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes, and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn2+, while Fe2+ and Mn2+ are only partially counteractive. Our results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca2+, phorbol ester, or antigen.

Counter diffusion of zinc and iron in alluvial soil

International Nuclear Information System (INIS)

Rattan, R.K.; Deb, D.L.

1980-01-01

Half cell technique showed that an increase in moisture tension and CaCO 3 content caused reduction in the counter diffusion coefficients of zinc and iron in an alluvial soil. Increases in bulk density, ambient temperature and concentration of synthetic chelating agents e.g. EDTA and DTPA increased the counter diffusion coefficients of both zinc and iron. (author)

Determination of zinc by substoichiometric extraction with malonic anilide

International Nuclear Information System (INIS)

Dutta, J.; Basu, S.

1994-01-01

A substoichiometric radiochemical extraction method has been developed for the determination of zinc employing a new chelating agent e.g. malonic anilide, dissolved in a mixed organic solvent, MIBK and ether (3:1). The reagent was synthesized and characterized in our laboratory. The method developed was utilized to determine the zinc content in few common vegetable samples. (orig.)

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

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Mouret, Stéphane, E-mail: stephane.mouret@irba.fr [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Dorandeu, Frédéric [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Ecole du Val-de-Grâce, 1 place Alphonse Laveran, Paris (France); Boudry, Isabelle [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France)

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.

Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani.

Science.gov (United States)

Saini, Shalini; Bharati, Kavita; Shaha, Chandrima; Mukhopadhyay, Chinmay K

2017-09-05

Micronutrients are essential for survival and growth for all the organisms including pathogens. In this manuscript, we report that zinc (Zn) chelator N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen Leishmania donovani (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant Leishmania is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.

Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.

Science.gov (United States)

Suh, Sang Won

2009-02-15

Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic neurons. In the present work I have extended those findings in three ways: (i) providing evidence that zinc translocation occurs into apical dendrites, (ii) presenting data that there is an apparent translocation into apical dendrites when only a zinc-containing synaptic input is stimulated, and (iii) presenting data that there is no zinc translocation into apical dendrite of ZnT3 KO mice following electrical stimulation. Hippocampal slices were preloaded with the "trappable" zinc fluorescent probe, Newport Green. After washout, a single apical dendrite in the stratum radiatum of hippocampal CA1 area was selected and focused on. Burst stimulation (100Hz, 500microA, 0.2ms, monopolar) was delivered to either the adjacent Schaffer-collateral inputs (zinc-containing) or to the adjacent temporo-ammonic inputs (zinc-free) to the CA1 dendrites. Stimulation of the Schaffer collaterals increased the dendritic fluorescence, which was blocked by TTX, low-Ca medium, or the extracellular zinc chelator, CaEDTA. Stimulation of the temporo-ammonic pathway caused no significant rise in the fluorescence. Genetic depletion of vesicular zinc by ZnT3 KO showed no stimulation-induced apical dendrite zinc rise. The present study provides evidence that synaptically released zinc translocates into postsynaptic neurons through the apical dendrites of CA1 pyramidal neurons during physiological synaptic activity.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

International Nuclear Information System (INIS)

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

2015-01-01

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn 2+ and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase + was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights: �

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui, E-mail: Donghuixu007@163.com

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights: �

Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase*

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Li, Qian; Li, Chuanyu; Mahtani, Harry K.; Du, Jian; Patel, Aashka R.; Lancaster, Jack R.

2014-01-01

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with •NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged •NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief •NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1–2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief •NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of •NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of •NO. PMID:24891512

METALS IN THE METABOLISM OF HIPPOCAMPUS AND ROLE OF ZINC IN THE PATHOGENESIS OF EPILEPTIC SEIZURES

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O. M. Kuchkovsky

2016-05-01

Full Text Available Physiological mechanisms of convulsions status during epilepsy or episindrom significantly different from the mechanisms, which were describe for other disorders associated with glutamatergic system, such as schizophrenia (a decrease of glutamate in neurons and increased dopaminergic load, drug addiction and alcoholism (the formation of endogenous opioids and dopamine, strengthening the role of GABA-ergic system. With glutamatergic transmission are сconnect not only convulsive state, but also the realization of higher integrative functions. Therefore, the development of epilepsy, particularly  which caused glutamate, implemented by activating Zn-ergic hippocampal neurons, associate with complex changes in human mental functions. Based on a scientific literature about  of the role of chelating zinc in the mechanisms of glutamatergic transmission, we can  suggest it participation in the mechanisms of formation of epilepsy  convulsions. In experience on animals, was show that in the animal organism of stressing correlative changes observe zinc content and secretory material in the hippocampus, Paneth cells  and B cells of pancreas. The nature of the changes depend on the stressor. When this change of zinc content in the hippocampus and hypothalamus (as the main regulator of stress reaction were multidirectional that this can be explained by the release of metal together with secretory material in the hypothalamus into the bloodstream. Research epileptic activity  of hippocampus by administering to the animal chelate 8 BSQ allowed to establish the dependence between convulsant action  and first  stress condition of the animal. Evocation of stress by 8-BSQ and physical activity, immobilization and alcohol abuse found that the convulsive effect of this reagent during intravitreal research increased in the case of prior exposure by specified kinds of stressors. In this pre-convulsive effect on exertion increased by 266% and the zinc content

Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

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Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

2006-01-01

Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

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Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

2013-06-01

Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

Zinc signaling in the hippocampus and its relation to pathogenesis of depression.

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Takeda, Atsushi

2012-06-01

Histochemically reactive zinc (Zn(2+)) is co-released with glutamate from zincergic neurons, a subclass of glutamatergic neurons. Zn(2+) serves as a signal factor in both the extracellular and intracellular compartments. Glucocorticoid-glutamatergic interactions have been proposed as a potential model to explain stress-mediated impairment of hippocampal function, i.e., cognition. However, it is unknown whether glucocorticoid-zincergic interactions are involved in this impairment. In the present study, involvement of synaptic Zn(2+) in stress-induced attenuation of CA1 LTP was examined in hippocampal slices from young rats after exposure to tail suspension stress for 30s, which significantly increased serum corticosterone. Stress-induced attenuation of CA1 LTP was ameliorated by administration of clioquinol, a membrane permeable zinc chelator, to rats prior to exposure to stress, implying that the reduction of synaptic Zn(2+) by clioquinol participates in this amelioration. To pursue the involvement of corticosterone-mediated Zn(2+) signal in the attenuated CA1 LTP by stress, dynamics of synaptic Zn(2+) was checked in hippocampal slices exposed to corticosterone. Corticosterone increased extracellular Zn(2+) levels measured with ZnAF-2 dose-dependently, as well as the intracellular Ca(2+) levels measured with calcium orange AM, suggesting that corticosterone excites zincergic neurons in the hippocampus and increases Zn(2+) release from the neuron terminals. Intracellular Zn(2+) levels measured with ZnAF-2DA were also increased dose-dependently, but not in the coexistence of CaEDTA, a membrane-impermeable zinc chelator, suggesting that intracellular Zn(2+) levels is increased by the influx of extracellular Zn(2+). Furthermore, corticosterone-induced attenuation of CA1 LTP was abolished in the coexistence of CaEDTA. The present study suggests that corticosterone-mediated increase in postsynaptic Zn(2+) signal in the cytosolic compartment is involved in the attenuation

Chelated mineral supplements for Nelore: quality and early embryonic development

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Camila Pasa

2014-01-01

Full Text Available ABSTRACT. Pasa C., Hatamoto-Zervoudakis L.K., Zervoudakis J.T. & Soares L. [Chelated mineral supplements for Nelore: quality and early embryonic development.] Suplementos minerais quelatados para vacas Nelore: qualidade e desenvolvimento embrionário inicial. Revista Brasileira de Medicina Veterinária, 36(1:29-34, 2014. Programa de Pós-Graduação em Ciência Animal, Faculdade de Agronomia e Medicina Veterinária, Universidade Federal do Mato Grosso, Av. Fernando Corrêa da Costa, 2367, Bairro Boa Esperança, Cuiabá, MT 78060-900, Brasil. E-mail: pasa_camila@hotmail.com The objective of this study was to evaluate the quality and early development of embryos produced with oocytes of cows supplemented with copper, zinc and selenium in a non-chelated and chelated. The experiment was conducted in Cuiabá-MT during the months April to July 2009. We used 24 adult Nellore multiparous, aged, average weights of the initial 36 months, 395 kg and mean body condition score 4.8, respectively randomly divided into 2 groups: control group (CG, supplemented with conventional mineral and Supplemented Group (GS, animals supplemented with zinc, copper and selenium chelated. Each group was kept in a paddock of Brachiaria brizantha cv Marandu received 1 kg of animal per day. chelated mineral supplementation (GS and conventional mineral (GC delivered via the protein supplement was given during a period of 99 days with daily average 1kg/cabeça. During the experimental period were two follicular aspirations, one to 59 days and another at 99 days of supplementation. Every two weeks the animals were weighed and ECC evaluated. oocytes viable (grades I, II and III were used for in vitro production of embryos. The experiment was completely randomized and data were analyzed by ANOVA and a significance level of 10%. There was no effect (p> 0.10 of supplementation with chelated minerals on the percentage of cleaved oocytes, total embryos produced, percentage of produced

Effects of phytase, cellulase, and dehulling treatments on iron and zinc in vitro solubility in faba bean (Vicia faba L.) Flour and Legume Fractions.

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Luo, Yu-Wei; Xie, Wei-Hua; Cui, Qun-Xiang

2010-02-24

Simulations of gastrointestinal digestion were used to try to identify the nature of the complexes between antinutritional factors and iron and zinc in faba bean and legume fractions. In digestible residue of raw faba bean flour, simultaneous action of cellulase and phytases made it possible to release about 28% units more iron than that released with the treatment without enzymes. About 49.8% of iron in raw faba bean flour was solubilized after in vitro digestion and simultaneous action of cellulase and phytase. In the hull fraction, the action of phytases and the simultaneous action of cellulase and phytase allowed about 7 and 35% units of additional zinc to be solubilized, respectively. Single enzymatic degradation of phytates from dehulled faba bean allowed solubilization from 65 to 93% of zinc, depending upon the treatment. In dehulled faba bean, iron was chelated by phytates and by fibers, whereas zinc was almost exclusively chelated by phytates. In the hull of faba bean, a high proportion of iron was chelated by iron-tannins, while the rest of iron as well as the majority of zinc were chelated in complexes between phytates and fibers.

Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators.

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Tõugu, Vello; Karafin, Ann; Zovo, Kairit; Chung, Roger S; Howells, Claire; West, Adrian K; Palumaa, Peep

2009-09-01

Aggregation of amyloid-beta (Abeta) peptides is a central phenomenon in Alzheimer's disease. Zn(II) and Cu(II) have profound effects on Abeta aggregation; however, their impact on amyloidogenesis is unclear. Here we show that Zn(II) and Cu(II) inhibit Abeta(42) fibrillization and initiate formation of non-fibrillar Abeta(42) aggregates, and that the inhibitory effect of Zn(II) (IC(50) = 1.8 micromol/L) is three times stronger than that of Cu(II). Medium and high-affinity metal chelators including metallothioneins prevented metal-induced Abeta(42) aggregation. Moreover, their addition to preformed aggregates initiated fast Abeta(42) fibrillization. Upon prolonged incubation the metal-induced aggregates also transformed spontaneously into fibrils, that appear to represent the most stable state of Abeta(42). H13A and H14A mutations in Abeta(42) reduced the inhibitory effect of metal ions, whereas an H6A mutation had no significant impact. We suggest that metal binding by H13 and H14 prevents the formation of a cross-beta core structure within region 10-23 of the amyloid fibril. Cu(II)-Abeta(42) aggregates were neurotoxic to neurons in vitro only in the presence of ascorbate, whereas monomers and Zn(II)-Abeta(42) aggregates were non-toxic. Disturbed metal homeostasis in the vicinity of zinc-enriched neurons might pre-dispose formation of metal-induced Abeta aggregates, subsequent fibrillization of which can lead to amyloid formation. The molecular background underlying metal-chelating therapies for Alzheimer's disease is discussed in this light.

Comments on chelation therapy

International Nuclear Information System (INIS)

Wrenn, M.E.

1981-01-01

The primary purpose of actinide chelation is to decrease the risk from radiation-induced cancer. While occupational exposures in the past have mainly involved low specific activity 239 Pu, future exposures will increasingly involve high specific activity plutonium, americium, and curium - all of which clear more rapidly from the lung. This will tend to shift the cancer risk from lung to bone and liver. Although therapy with Ca- or Zn-DTPA rapidly removes 241 Am from the canine, the sub-human primate, and the human liver, improved methods for removal from bone and lung are needed. DTPA can remove 241 Am more easily from the growing skeleton of a child than from the mature skeleton of an adult. Investigators at Karlsruhe are developing chelation agents for oral administration and are investigating the reduction in local dose to bone resulting from chelation therapy

Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

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Park, Sung-Soo; Bae, Insoo; Lee, Yong J

2008-04-15

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

Zinc and Copper Effects on Stability of Tubulin and Actin Networks in Dendrites and Spines of Hippocampal Neurons.

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Perrin, Laura; Roudeau, Stéphane; Carmona, Asuncion; Domart, Florelle; Petersen, Jennifer D; Bohic, Sylvain; Yang, Yang; Cloetens, Peter; Ortega, Richard

2017-07-19

Zinc and copper ions can modulate the activity of glutamate receptors. However, labile zinc and copper ions likely represent only the tip of the iceberg and other neuronal functions are suspected for these metals in their bound state. We performed synchrotron X-ray fluorescence imaging with 30 nm resolution to image total biometals in dendrites and spines from hippocampal neurons. We found that zinc is distributed all along the dendrites while copper is mainly pinpointed within the spines. In spines, zinc content is higher within the spine head while copper is higher within the spine neck. Such specific distributions suggested metal interactions with cytoskeleton proteins. Zinc supplementation induced the increase of β-tubulin content in dendrites. Copper supplementation impaired the β-tubulin and F-actin networks. Copper chelation resulted in the decrease of F-actin content in dendrites, drastically reducing the number of F-actin protrusions. These results indicate that zinc is involved in microtubule stability whereas copper is essential for actin-dependent stability of dendritic spines, although copper excess can impair the dendritic cytoskeleton.

Nitrosothiol formation and protection against Fenton chemistry by nitric oxide-induced dinitrosyliron complex formation from anoxia-initiated cellular chelatable iron increase.

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Li, Qian; Li, Chuanyu; Mahtani, Harry K; Du, Jian; Patel, Aashka R; Lancaster, Jack R

2014-07-18

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Phytase activity, phytic acid, zinc, phosphorus and protein contents ...

African Journals Online (AJOL)

STORAGESEVER

2009-09-15

Sep 15, 2009 ... Key words: Zinc, nitrogen, phosphorus, phytic acid, phytase. .... speculated that the synthesizing metabolism of grain PA probably was closely ..... Efficiency when Grown in the Chelate-Buffered Nutrient Solution. II. Nutrient ...

Co-induction of p75NTR and p75NTR-associated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat.

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Park, J A; Lee, J Y; Sato, T A; Koh, J Y

2000-12-15

Recently, a 22 kDa protein termed p75(NTR)-associated death executor (NADE) was discovered to be a necessary factor for p75(NTR)-mediated apoptosis in certain cells. However, the possible role for p75(NTR)/NADE in pathological neuronal death has yet been undetermined. In the present study, we have examined this possibility in vivo and in vitro. Exposure of cortical cultures to zinc induced both p75(NTR) and NADE in neurons, whereas exposure to NMDA, ionomycin, iron, or H(2)O(2) induced neither. In addition, zinc exposure increased neuronal NGF expression and its release into the medium. A function-blocking antibody of p75(NTR) (REX) inhibited association between p75(NTR) and NADE as well as neuronal death induced by zinc. Conversely, NGF augmented zinc-induced neuronal death. Caspase inhibitors reduced zinc-induced neuronal death, indicating that caspases were involved. Because reduction of NADE expression with cycloheximide or NADE antisense oligonucleotides attenuated zinc-induced neuronal death, NADE appears to contribute to p75(NTR)-induced cortical neuronal death as shown in other cells. Because zinc neurotoxicity may be a key mechanism of neuronal death after transient forebrain ischemia, we next examined this model. After ischemia, p75(NTR) and NADE were induced in degenerating rat hippocampal CA1 neurons. There was a close correlation between zinc accumulation and p75(NTR)/NADE induction. Suggesting the role of zinc here, injection of a metal chelator, CaEDTA, into the lateral ventricle completely blocked the induction of p75(NTR) and NADE. Our results suggest that co-induction of p75(NTR) and NADE plays a role in zinc-triggered neuronal death in vitro and in vivo.

Monitoring the effects of chelating agents and electrical fields on active forms of Pb and Zn in contaminated soil.

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Tahmasbian, Iman; Safari Sinegani, Ali Akbar

2013-11-01

The application of electrical fields and chelating agents is an innovative hybrid technology used for the decontamination of soil polluted by heavy metals. The effects of four center-oriented electrical fields and chelating agents on active fractions of lead and zinc were investigated in this pot experiment. Ethylenediaminetetraacetic acid (EDTA) as a synthetic chelator and cow manure extract (CME) and poultry manure extract (PME) as natural chelators were applied to the pots (2 g kg(-1)) 30 days after the first irrigation. Two weeks later, four center-oriented electrical fields were applied in each pot (in three levels of 0, 10, and 30 V) for 1 h each day for 14 days. The soil near the cathode and anodes was collected and analyzed as cathodic and anodic soil, respectively. Results indicated that the soluble-exchangeable fraction of lead and zinc were decreased in the cathodic soil, while the carbonate-bound fractions were increased. In the anodic soil, however, the opposite result was observed. EDTA enhanced the soluble-exchangeable form of the metals in both anodic and cathodic soils. Furthermore, the amounts of carbonate-bound heavy metals were increased by the application of CME in both soils. The organic-bound fraction of the metals was increased by the application of natural chelators, while electrical fields had no significant impacts on this fraction.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

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Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

Negative modulation of presynaptic activity by zinc released from Schaffer collaterals.

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Takeda, Atsushi; Fuke, Sayuri; Tsutsumi, Wataru; Oku, Naoto

2007-12-01

The role of zinc in excitation of Schaffer collateral-CA1 pyramidal cell synapses is poorly understood. Schaffer collaterals stained with ZnAF-2 or ZnAF-2DA, a membrane-impermeable or a membrane-permeable zinc indicator, respectively, were treated by tetanic stimulation (200 Hz, 1 sec). Extracellular and intracellular ZnAF-2 signals were increased in the stratum radiatum of the CA1, in which Schaffer collateral synapses exist. Both the increases were completely blocked in the presence of 1 mM CaEDAT, a membrane-impermeable zinc chelator, suggesting that 1 mM CaEDTA is effective for chelating zinc released from Schaffer collaterals. The role of Schaffer collateral zinc in presynaptic activity was examined by using FM4-64, a fluorescent indicator for vesicular exocytosis. The decrease in FM4-64 signal during tetanic stimulation (10 Hz, 180 sec) was enhanced in Schaffer collaterals in the presence of 1 mM CaEDTA but suppressed in the presence of 5 microM ZnC1(2), suggesting that zinc released from Schaffer collaterals suppresses presynaptic activity during tetanic stimulation. When Schaffer collateral synapses stained with calcium orange AM, a membrane-permeable calcium indicator, were regionally stimulated with 1 mM glutamate, calcium orange signal was increased in the CA1 pyramidal cell layer. This increase was enhanced in the presence of CaEDTA and attenuated in the presence of zinc. These results suggest that zinc attenuates excitation of Schaffer collateral synapses elicited with glutamate via suppression of presynaptic activity. (c) 2007 Wiley-Liss, Inc.

TEM and SEM observation of uranium induced renal necrosis and the result of chelates treatment on rats

International Nuclear Information System (INIS)

Sun Shiquan; Li Baoxing; Lai Chixiang; You Zhanyun

1987-01-01

The TEM (transmission electron microscope) and SEM (scanning electron microscope) observation of uranium induced renal necrosis and the result of chelates treatment on rats are reported. Ultrastructural changes in kidney related with the impairment of intracellular fluid transportation can be found after acute uranium intoxication in rats, such as: condensation and swelling of mitochondria, matrix edema, dilatation of intercellular space, disappearance of basal folds, thickening of basal web, intensification of basal lamina of the proximal convoluted tubule epithelium cells, and foot processes swelling, diminishing of endothelium fenestrae of the renal glomerulus. Heavy metal chelates DTPA and H-73-10 treatment may result in intracellular fluid accumulation and condensed grannule formation in lysosome. Treatment with these chelates in the critical stage of uranium intoxication may accelerate the necrosis instead of diminishing. This may be related to the augment of the load of lysosome and intracellular system of fluid transportation

Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

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Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

2017-01-01

Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

Directory of Open Access Journals (Sweden)

Bryan E Bunnell

Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

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Singla, Neha; Dhawan, D K

2017-01-01

Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

Zinc promotes the death of hypoxic astrocytes by upregulating hypoxia-induced hypoxia-inducible factor-1alpha expression via poly(ADP-ribose) polymerase-1.

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Pan, Rong; Chen, Chen; Liu, Wen-Lan; Liu, Ke-Jian

2013-07-01

Pathological release of excess zinc ions has been implicated in ischemic brain cell death. However, the underlying mechanisms remain to be elucidated. In stroke, ischemia-induced zinc release and hypoxia-inducible factor-1 (HIF-1) accumulation concurrently occur in the ischemic tissue. The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP-1 and HIF-1α during hypoxia, which significantly contributes to cell death during ischemia. Primary cortical astrocytes and C8-D1A cells were exposed to different concentrations of zinc chloride. Cell death rate and protein expression of HIF-1 and Poly(ADP-ribose) polymerase (PARP)-1 were examined after 3-h hypoxic treatment. Although 3-h hypoxia or 100 μM of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc-concentration-dependent manner. Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF-1α protein, which was further augmented by added exogenous zinc. Notably, HIF-1α knockdown blocked zinc-induced astrocyte death. Moreover, knockdown of PARP-1, another important protein in the response of hypoxia, attenuated the overexpression of HIF-1α and reduced the cell death rate. Our studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF-1α via the cell fate determine factor PARP-1 modification, which provides a novel mechanism for zinc-mediated ischemic brain injury. © 2013 John Wiley & Sons Ltd.

Lead and zinc intoxication in companion birds.

Science.gov (United States)

Puschner, Birgit; Poppenga, Robert H

2009-01-01

Although the toxicity of lead and zinc to birds is widely recognized by veterinarians and bird owners, these metals are frequently found in the environments of pet and aviary birds, and intoxications are common. Clinical signs exhibited by intoxicated birds are often nonspecific, which makes early diagnosis difficult. Fortunately, lead and zinc analyses of whole blood and serum or plasma, respectively, are readily available and inexpensive; elevated concentrations can confirm intoxication. Once diagnosed, intoxication can be effectively treated by (1) preventing further exposure, (2) administering chelating drugs, and (3) providing symptomatic and supportive care.

Deaths associated with hypocalcemia from chelation therapy--Texas, Pennsylvania, and Oregon, 2003-2005.

Science.gov (United States)

2006-03-03

Chelating agents bind lead in soft tissues and are used in the treatment of lead poisoning to enhance urinary and biliary excretion of lead, thus decreasing total lead levels in the body. During the past 30 years, environmental and dietary exposures to lead have decreased substantially, resulting in a considerable decrease in population blood lead levels (BLLs) and a corresponding decrease in the number of patients requiring chelation therapy. Chelating agents also increase excretion of other heavy metals and minerals, such as zinc and, in certain cases, calcium. This report describes three deaths associated with chelation-therapy--related hypocalcemia that resulted in cardiac arrest. Several drugs are used in the treatment of lead poisoning, including edetate disodium calcium (CaEDTA), dimercaperol (British anti-Lewisite), D-penicillamine, and meso-2,3-dimercaptosuccinic acid (succimer). Health-care providers who are unfamiliar with chelating agents and are considering this treatment for lead poisoning should consult an expert in the chemotherapy of lead poisoning. Hospital pharmacies should evaluate whether continued stocking of Na2EDTA is necessary, given the established risk for hypocalcemia, the availability of less toxic alternatives, and an ongoing safety review by the Food and Drug Administration (FDA). Health-care providers and pharmacists should ensure that Na2EDTA is not administered to children during chelation therapy.

Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

Science.gov (United States)

Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

2012-07-01

LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

Development of iron chelators for Cooley's anemia. Final report

International Nuclear Information System (INIS)

Crosby, W.H.; Green, R.

1982-01-01

Iron chelators were screened in an iron-loaded rat model using selective radioiron probes. In all experiments, chelators D and F, in that order, induced significant loss of radioiron compared with controls. However, use of chelator D was associated with side effects, and resulted in the death of some animals. There was some evidence that chelator A also caused iron loss significantly greater than controls. Chelators B, C and E were without apparent enhancing effect on radioiron excretion. This was a blind study and the compounds used were A - 2,3-Dihydroxybenzoic acid; B - N,N1-Dimethyladipohydroxamic acid; C - DL-Phenylalanine hydroxamic acid; D - Ethylenediamine-N,N1-bis(2-hydroxphenylacetic acid); E - Propionohydroxamic acid; and F - Deferrioxamine B

Iron chelators ICL670 and 311 inhibit HIV-1 transcription

International Nuclear Information System (INIS)

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

2007-01-01

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

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

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Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

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Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

2018-01-15

Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Allergic contact dermatitis induced by zinc pyrithione in shampoo: a case report

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Chih-Wei Hsieh

2010-12-01

Full Text Available Shampoo-induced allergic contact dermatitis is difficult to diagnose clinically because it can involve multiple and variable areas where the shampoo flows. Zinc pyrithione is a common active agent in medicated shampoo that is known to have good anti-dandruff and antifungal effects. Despite its low risk of sensitization, cases of allergic contact dermatitis still occur because of the popularity of such products. We report a 33-year-old man who developed pruritic rash on his scalp, face, neck, and hands after using a new shampoo containing zinc pyrithione. A patch test revealed a positive reaction to zinc pyrithione and personal shampoo containing zinc pyrithione.

STUDIES REGARDING THE CHELATE-INDUCED HYPERACCUMULATION OF CU AND FE USING LOLIUM PERENNE SPECIES IN MINING AREAS

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ANCA-DIANA PRICOP

2009-05-01

Full Text Available The plant capacity to absorb high amounts of metal for a short period of time is the major factor that influences the efficiency of phytoextraction. The hyperaccumulating plants uptake high amounts in their tissues correlated to the metal concentrations in soil. Chelating agents have the capacity to induce the metal accumulation in biomass. They increase metal bioavailability for plants by releasing the metal in accessible forms. The present study emphasizes that in the case of EDTA use, the obtained biomass is smaller compared to the other variants, showing a lower tolerance to this chelating agent of Lolium perenne species. Cu and Fe phytoextraction by Lolium perenne species is higher in the case of EDTA use. Cu bioaccumulation has higher values in variants with compost-sterile mixture ratio of 1:4 in comparison with Fe. In the case of the best compost-sterile mixture ratio of 1:3 the highest biomass is obtained in all the variants, biosolids’ effect being stronger compared to the chelating agent.

Enhanced removal of 241Am by DTPA chelation therapy in an adult and teenage subject

International Nuclear Information System (INIS)

Sasso, T.L.; Cohen, N.

1975-01-01

A series of Na 3 (Ca-DTPA) chelation treatments were carried out on two human subjects, an adult man and a teenage boy, who have long-term body burdens of 241 Am. The in vivo whole-body counting, bioassay of urine and feces, and various blood chemistry measurements were coordinated to coincide with this therapy schedule. Decreases in total body burdens for this treatment period were measured as 5 percent in the adult and 30 percent in the youth. High concentrations of zinc in urine and a corresponding decrease of activity of the zinc-dependent erythropoietic enzyme, ALAD, were also observed. (U.S.)

Novel chelating agents for iron, manganese, zinc, and copper mixed fertilisation in high pH soil-less cultures.

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López-Rayo, Sandra; Nadal, Paloma; Lucena, Juan J

2016-03-15

Studies about simultaneous fertilisation with several micronutrients have increased in recent years, as Fe, Mn and Zn deficiencies may appear in the same culture conditions. In fertigation, the replacement of sulfates by synthetic chelates is essential in areas with high pH irrigation water and substrates. Ethylenediamine-N-(2-hydroxyphenylacetic acid)-N'-(4-hydroxyphenylacetic acid) (o,p-EDDHA) and ethylenediamine disuccinic acid (EDDS) are novel chelating agents whose efficacy in simultaneous fertilisation of Zn, Mn and Cu is unknown. This work evaluates the effectiveness of both ligands compared to traditional ligands (EDTA, HEEDTA and DTPA) applied as micronutrient chelate mixtures to soybean and navy bean plants grown in soil-less cultures at high pH by analysing the SPAD and micronutrient nutritional status, including the Composition Nutritional Diagnosis (CND) analysis tool. The application of micronutrients using o,p-EDDHA was more effective in providing Mn and Zn than traditional ligands or sulfates. The application using EDDS increased the Zn nutrition. The results are well correlated with the chemical stability of the formulations. The combined application of Mn and Zn as o,p-EDDHA chelates can represent a more effective source than traditional chelates in micronutrient fertiliser mixtures in soil-less cultures at a high pH. © 2015 Society of Chemical Industry.

Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

Science.gov (United States)

Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

2007-02-01

Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

Syntheses, structures and luminescence behaviour of some zinc(II ...

Indian Academy of Sciences (India)

2, the zinc(II) centre is bound by four N atoms of the tailored Schiff base L2 and two O atoms of the chelated acetate. .... determination parameters for 1 and 2 is given in table 1. 3. Results ..... Shields G P, Taylor R, Towler M and van de Streek J.

Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

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John T Murphy

2011-03-01

Full Text Available Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1 gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.

Functional role of zinc in poly(A) synthesis catalyzed by nuclear poly(A) polymerase

Energy Technology Data Exchange (ETDEWEB)

Rose, K M; Allen, M S; Crawford, I L; Jacob, S T [Pennsylvania State Univ., Hershey (USA). Dept. of Pharmacology; Pennsylvania State Univ., Hershey (USA). Specialized Cancer Research Center; Texas Univ., Dallas (USA). Dept. of Neurology; Texas Univ., Dallas (USA). Dept. of Pharmacology)

1978-07-01

The functional role of transition metals in poly(A) synthesis was elucidated by investigating the effect of the metal chelator o-Phenanthroline on purified nuclear poly(A) polymerase. This chelator inhibited the enzyme activity in a manner competitive with respect to the polynucleotide primer concentration. o-phenanthroline was a non-competitive inhibitor with regard to ATP concentration and an 'uncompetitive' inhibitor with regard to dithiothreitor levels. The metal content of the purified enzyme preparations from rat liver and Morris hepatoma 3924A was determined using atomic absorption spectrometry. Of the transition metals measured, only zinc was present in detectable quantities at levels less than 1 mol/mol of enzyme. Hepatoma enzyme contained 2-3 times as much zinc as the corresponding liver enzyme. Hepatoma poly(A) polymerase was also radioactively labelled in vivo by injection of tumor-bearing animals with /sup 65/Zn. Dialysis experiments with highly purified radiolabelled poly(A) polymerase showed that the enzyme-zinc complex was labile and that a reduction in /sup 65/Zn content correlated with a loss in enzyme activity.

Functional role of zinc in poly(A) synthesis catalyzed by nuclear poly(A) polymerase

International Nuclear Information System (INIS)

Rose, K.M.; Allen, M.S.; Crawford, I.L.; Jacob, S.T.; Pennsylvania State Univ., Hershey; Texas Univ., Dallas; Texas Univ., Dallas

1978-01-01

The functional role of transition metals in poly(A) synthesis was elucidated by investigating the effect of the metal chelator o-phenanthroline on purified nuclear poly(A) polymerase. This chelator inhibited the enzyme activity in a manner competitive with respect to the polynucleotide primer concentration. o-phenanthroline was a non-competitive inhibitor with regard to ATP concentration and an 'uncompetitive' inhibitor with regard to dithiothreitor levels. The metal content of the purified enzyme preparations from rat liver and Morris hepatoma 3924A was determined using atomic absorption spectrometry. Of the transition metals measured, only zinc was present in detectable quantities, at levels less than 1 mol/mol of enzyme. Hepatoma enzyme contained 2-3 times as much zinc as the corresponding liver enzyme. Hepatoma poly(A) polymerase was also radioactively labelled in vivo by injection of tumor-bearing animals with 65 Zn. Dialysis experiments with highly purified radiolabelled poly(A) polymerase showed that the enzyme-zinc complex was labile and that a reduction in 65 Zn content correlated with a loss in enzyme activity. (orig./AJ) [de

Mutation of a zinc-binding residue in the glycine receptor α1 subunit changes ethanol sensitivity in vitro and alcohol consumption in vivo.

Science.gov (United States)

McCracken, Lindsay M; Blednov, Yuri A; Trudell, James R; Benavidez, Jillian M; Betz, Heinrich; Harris, R Adron

2013-02-01

Ethanol is a widely used drug, yet an understanding of its sites and mechanisms of action remains incomplete. Among the protein targets of ethanol are glycine receptors (GlyRs), which are potentiated by millimolar concentrations of ethanol. In addition, zinc ions also modulate GlyR function, and recent evidence suggests that physiologic concentrations of zinc enhance ethanol potentiation of GlyRs. Here, we first built a homology model of a zinc-bound GlyR using the D80 position as a coordination site for a zinc ion. Next, we investigated in vitro the effects of zinc on ethanol action at recombinant wild-type (WT) and mutant α1 GlyRs containing the D80A substitution, which eliminates zinc potentiation. At D80A GlyRs, the effects of 50 and 200 mM ethanol were reduced as compared with WT receptors. Also, in contrast to what was seen with WT GlyRs, neither adding nor chelating zinc changed the magnitude of ethanol enhancement of mutant D80A receptors. Next, we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1(D80A) knock-in (KI) mice. The KI mice showed decreased ethanol consumption and preference, and they displayed increased startle responses compared with their WT littermates. Other behavioral tests, including ethanol-induced motor incoordination and strychnine-induced convulsions, revealed no differences between the KI and WT mice. Together, our findings indicate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc binding at the D80 position may be important for mediating some of the behavioral effects of ethanol action at GlyRs.

Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

Energy Technology Data Exchange (ETDEWEB)

King, A.B.; Schwartz, R.

1987-04-01

Ethambutol, (CH/sub 3/CH/sub 2/-CH(CH/sub 2/OH)-NH-CH/sub 2/)/sub 2/ (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by /sup 65/Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, /sup 65/Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption.

Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

International Nuclear Information System (INIS)

King, A.B.; Schwartz, R.

1987-01-01

Ethambutol, [CH 3 CH 2 -CH(CH 2 OH)-NH-CH 2 ] 2 (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by 65 Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, 65 Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption

Zinc-induced Self-association of Complement C3b and Factor H

Science.gov (United States)

Nan, Ruodan; Tetchner, Stuart; Rodriguez, Elizabeth; Pao, Po-Jung; Gor, Jayesh; Lengyel, Imre; Perkins, Stephen J.

2013-01-01

The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 μm zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 μm zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 μm zinc and even more so at >100 μm zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients. PMID:23661701

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

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Leonardo Victor Barbosa Pereira

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

Understanding Zinc Quantification with Existing and Advanced Ditopic Fluorescent Zinpyr Sensors

Science.gov (United States)

Buccella, Daniela; Horowitz, Joshua A.; Lippard, Stephen J.

2011-01-01

Treatment of aqueous zinc solutions with incremental additions of a ditopic fluorescent sensor of the Zinpyr family, based on pyridine/pyrazine-containing metal recognition units, affords a fluorescence titration curve with a sharp maximum at a sensor:Zn2+ ratio of 0.5 (Zhang, X-a.; Hayes, D.; Smith, S. J.; Friedle, S.; Lippard, S. J. J. Am. Chem Soc. 2008, 130, 15788–15789). This fluorescence response enables the quantification of readily chelatable zinc in biological samples by a simple titration protocol. In the present work a new set of ditopic fluorescence zinc sensors functionalized with pyridine/pyrazine-containing metal chelating units is described, and through detailed studies the principles governing the characteristic “OFF-ON-OFF” fluorescence behavior and quantification capabilities of the family are delineated. Incorporation of carboxylate/ester groups in the 6 position of the fluorescein allows for control of the spatial distribution of the sensor for selective extra- or intracellular imaging of mobile zinc, without introducing significant changes in zinc-binding properties. A combination of spectrophotometric and potentiometric measurements provided a complete description of the H+ and Zn2+ binding properties of the compounds and their correlation with the observed fluorescence profile. The first zinc-binding event has an apparent affinity, K1′, of 1.9–3.1×109 M−1, whereas for coordination of the second Zn2+ ion, responsible for fluorescence turn on, the apparent formation constant K2′ is 5.5–6.9×107 M−1. A detailed chemical and mathematical analysis of the system demonstrated that the difference in emission efficiencies of the dimetalated (LZn2) vs. monometalated (LZn) and metal free (L) forms, a consequence of the combined quenching effects of the two metal-chelating units, significantly influences the shape of the titration curve. The scope of the titration method was investigated mathematically, and a lower boundary for the

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

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Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (Ptaurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (PTaurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (Ptaurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Chloroquine is a zinc ionophore.

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Jing Xue

Full Text Available Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780. Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.

Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure.

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Kirsten, Thiago B; Queiroz-Hazarbassanov, Nicolle; Bernardi, Maria M; Felicio, Luciano F

2015-06-01

Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

Soil micronutrients and its uptake by rice plant. Part of a coordinated programme on isotope-aided micronutrient studies in rice production with special reference to zinc deficiencies

International Nuclear Information System (INIS)

Kim, T.S.

1980-02-01

A series of field and greenhouse experiments with flooded rice was carried out on contrasting soil types of Korea to study the zinc status of soils, evaluate the chemical methods for extracting zinc from soils in terms of ability to identify zinc deficiency, perform 65 Zn-aided experiments including the residual effects of zinc fertilizers to evaluate the efficiency of zinc sources and methods of zinc application to rice, and associated studies on factors affecting zinc nutrition in rice such as effect of organic matter and chelates. The results show that i) 0.05 N HCl solution for extracting available zinc in soil was effective to separating the soils which require zinc fertilizer application. The proposed zinc value to identify is 2.4 ppm. Among rice soils surveyed, the red-yellow podsolic soil derived from basalt, the reddish-brown lateritic soil of calcareous material and newly reclaimed saline soils were shown to be below this limit; ii) 5 kg Zn/ha as zinc sulphate introduced the highest response in terms of % Zndff, total zinc yield in rice plant, and the fertilizer zinc use efficiency. Applying higher zinc amounts, in case of 20 kg Zn/ha, retarded nitrogen uptake by the plant and as a result the rice grain yield was decreased; iii) Significant yields increases due to the residual effects of zinc fertilizers were obtained on the second and third crops; iv) On the zinc-deficient calcareous soil the use of chelated zinc sources is recommended

Zinc release from Schaffer collaterals and its significance.

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Takeda, Atsushi; Nakajima, Satoko; Fuke, Sayuri; Sakurada, Naomi; Minami, Akira; Oku, Naoto

2006-02-15

On the basis of the evidence that approximately 45% of Schaffer collateral boutons are zinc-positive, zinc release from Schaffer collaterals and its action were examined in hippocampal slices. When zinc release from Schaffer collaterals was examined using ZnAF-2, a membrane-impermeable zinc indicator, ZnAF-2 signal in the stratum radiatum of the CA1 was increased by tetanic stimuli at 100 Hz for 1s, suggesting that zinc is released from Schaffer collaterals in a calcium- and impulse-dependent manner. An in vivo microdialysis experiment indicated that the perfusion with 10 microM zinc significantly decreases extracellular glutamate concentration in the CA1. When tetanic stimuli at 100 Hz for 5s were delivered to the dentate granule cells, the increase in calcium signal in the stratum radiatum of the CA1, as well as in the stratum lucidum of the CA3, was attenuated by addition of 10 microM zinc, while enhanced by addition of 1mM CaEDTA, a membrane-impermeable zinc chelator. The increase in calcium signal in the CA1, in which Schaffer collateral synapses exist, during delivery of tetanic stimuli at 100 Hz for 1s to the Schaffer collateral-commissural pathway was also significantly enhanced by addition of 1mM CaEDTA. These results suggest that zinc released from Schaffer collaterals suppressively modulates presynaptic and postsynaptic calcium signaling in the CA1, followed by the suppression of glutamate release.

Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc.

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Brownie, C F; Brownie, C; Noden, D; Krook, L; Haluska, M; Aronson, A L

1986-03-15

The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m2/day) of CaEDTA, two concentrations (8 and 20 mmol/m2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m2/day corresponding to 4 mmol/m2/day). Protection is afforded by incorporating zinc in the chelate.

Characterization of antibody-chelator conjugates: Determination of chelator content by terbium fluorescence titration

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Brandt, K.D.; Schnobrich, K.E.; Johnson, D.K. (Abbott Laboratories, Department 90M, Abbott Park, IL (United States))

1991-01-01

Fluorescence titrations were performed by adding varying mole ratios of terbium(III) to antibody conjugates formed by benzyl isothiocyanate derivatives of three different polyaminopolycarboxylate chelators (NTA, EDTA, and DTPA) and the results compared to values for average chelator content obtained by cobalt-57 binding assays. For two different murine monoclonal antibodies, the average chelator content obtained by terbium fluorescence titration correlated closely with that measured by the cobalt-57 binding assay. It is concluded that lanthanide fluorescence titrations provide a useful alternative to radiometal binding assays for the determination of chelator content in protein-chelator conjugates.

Characterization of antibody-chelator conjugates: Determination of chelator content by terbium fluorescence titration

International Nuclear Information System (INIS)

Brandt, K.D.; Schnobrich, K.E.; Johnson, D.K.

1991-01-01

Fluorescence titrations were performed by adding varying mole ratios of terbium(III) to antibody conjugates formed by benzyl isothiocyanate derivatives of three different polyaminopolycarboxylate chelators (NTA, EDTA, and DTPA) and the results compared to values for average chelator content obtained by cobalt-57 binding assays. For two different murine monoclonal antibodies, the average chelator content obtained by terbium fluorescence titration correlated closely with that measured by the cobalt-57 binding assay. It is concluded that lanthanide fluorescence titrations provide a useful alternative to radiometal binding assays for the determination of chelator content in protein-chelator conjugates

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

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Jitendra Kumar

Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

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Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

2016-01-01

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

Response of hippocampal mossy fiber zinc to excessive glutamate release.

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Takeda, Atsushi; Minami, Akira; Sakurada, Naomi; Nakajima, Satoko; Oku, Naoto

2007-01-01

The response of hippocampal mossy fiber zinc to excessive glutamate release was examined to understand the role of the zinc in excessive excitation in the hippocampus. Extracellular zinc and glutamate concentrations during excessive stimulation with high K(+) were compared between the hippocampal CA3 and CA1 by the in vivo microdialysis. Zinc concentration in the CA3 was more increased than that in the CA1, while glutamate concentration in the CA3 was less increased than that in the CA1. It is likely that more increase in extracellular zinc is linked with less increase in extracellular glutamate in the CA3. To see zinc action in mossy fiber synapses during excessive excitation, furthermore, 1mM glutamate was regionally delivered to the stratum lucidum in the presence of zinc or CaEDTA, a membrane-impermeable zinc chelator, and intracellular calcium signal was measured in the CA3 pyramidal cell layer. The persistent increase in calcium signal during stimulation with glutamate was significantly attenuated in the presence of 100 microM zinc, while significantly enhanced in the presence of 1mM CaEDTA. These results suggest that zinc released from mossy fibers attenuates the increase in intracellular calcium signal in mossy fiber synapses and postsynaptic CA3 neurons after excessive inputs to dentate granular cells.

Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

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Plapp, Bryce V.; Savarimuthu, Baskar Raj; Ferraro, Daniel J.; Rubach, Jon K.; Brown, Eric N.; Ramaswamy, S. (Iowa)

2017-07-07

During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ~1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.

Chelating polymeric membranes

KAUST Repository

Peinemann, Klaus-Viktor; Villalobos Vazquez de la Parra, Luis Francisco; Hilke, Roland

2015-01-01

microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

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Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

2015-12-05

Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chelation in Metal Intoxication

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Swaran J.S. Flora

2010-06-01

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

Chelation Therapy for Mercury Poisoning

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Rong Guan

2009-01-01

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

Response of extracellular zinc in the ventral hippocampus against novelty stress.

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Takeda, Atsushi; Sakurada, Naomi; Kanno, Shingo; Minami, Akira; Oku, Naoto

2006-10-01

An extensive neuronal activity takes place in the hippocampus during exploratory behavior. However, the role of hippocampal zinc in exploratory behavior is poorly understood. To analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. The same phenomenon was observed during exploratory behavior on day 2 and extracellular zinc had returned to the basal level during exploratory behavior on day 8. To examine the significance of the decrease in extracellular zinc in exploratory activity, exploratory behavior was observed during perfusion with 1 mm CaEDTA, a membrane-impermeable zinc chelator. Locomotor activity in the novel environment was decreased by perfusion with CaEDTA. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of the glutamatergic neurotransmitter system. The zinc uptake may be involved in the response to painless psychological stress or in the cognitive processes.

Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

Science.gov (United States)

Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

2012-05-01

Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. © 2011 Blackwell Verlag GmbH.

Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

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Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

2004-10-01

Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

Science.gov (United States)

Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

2010-03-01

In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

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Raul Hernandes Bortolin

Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

Quantitative property-property relationship (QPPR) approach in predicting flotation efficiency of chelating agents as mineral collectors.

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Natarajan, R; Nirdosh, I; Venuvanalingam, P; Ramalingam, M

2002-07-01

The QPPR approach has been used to model cupferrons as mineral collectors. Separation efficiencies (Es) of these chelating agents have been correlated with property parameters namely, log P, log Koc, substituent-constant sigma, Mullikan and ESP derived charges using multiple regression analysis. Es of substituted-cupferrons in the flotation of a uranium ore could be predicted within experimental error either by log P or log Koc and an electronic parameter. However, when a halo, methoxy or phenyl substituent was in para to the chelating group, experimental Es was greater than the predicted values. Inclusion of a Boolean type indicative parameter improved significantly the predictability power. This approach has been extended to 2-aminothiophenols that were used to float a zinc ore and the correlations were found to be reasonably good.

Protective effect of zinc aspartate against acetaminophen induced hepato-renal toxicity in albino rats

International Nuclear Information System (INIS)

Mohamed, E.T.; Said, A.I.; El-Sayed, S.A.

2011-01-01

Zinc is an essential nutrient that is required in humans and animals for many physiological functions, including antioxidant functions. The evidence to date indicates that zinc is an important element that links antioxidant system and tissue damage. Acetaminophen (AP), a widely used analgesic and antipyretic, produces hepatocyte and renal tubular necrosis in human and animals following overdose. In human, AP is one of the most common causes of acute liver failure as a result of accidental or deliberate overdose. Moreover, the initial event in AP toxicity is a toxic metabolic injury with the release of free radicals and subsequent cellular death by necrosis and apoptosis. This study was designed to evaluate the potential protective role of zinc aspartate in case of acetaminophen induced hepato-renal toxicity in rats. A total number of 32 adult male albino rats were divided into 4 equal groups: group I (control group), group II (zinc aspartate treated group), group III (acetaminophen treated group; by a single oral dose of 750 mg/kg body weight) and group IV acetaminophen plus zinc treated group; (zinc aspartate was intraperitoneally given one hour after acetaminophen administration in a dose of 30 mg/kg body weight). Serum levels of: alanine aminotransferase, aspartate aminotransferase, direct bilirubin, blood urea nitrogen, creatinine, uric acid, xanthine oxidase (XO), glutathione (GSH), malonaldehyde (MDA) and nitric oxide (NO) were assessed in all groups. The results of this study showed that treatment with acetaminophen alone (group III) produced a significant increase in serum levels of the liver enzymes and direct bilirubin. Moreover, in the same group there was a significant increase in the blood urea nitrogen and serum creatinine compared to the control group. In addition, there was a significant increase in XO and MDA and a significant decrease in GSH and NO level. Injection of rats with zinc aspartate after acetaminophen treatment could produce a

High temperature dissolution of ferrites, chromites and bonaccordite in chelating media

Energy Technology Data Exchange (ETDEWEB)

Sathyaseelan, V.S.; Subramanian, H.; Anupkumar, B.; Rufus, A.L.; Velmurugan, S.; Narasimhan, S.V., E-mail: snv@igcar.gov.in [BARC Facilities, Water and Steam Chemistry Div., Tamilnadu (India)

2010-07-01

Different methods have been employed world wide for the decontamination of reactor coolant system surfaces. The success of a decontamination process mainly depends on the oxide dissolution efficiency of the decontamination formulation. Among the oxides, Fe{sub 3}O{sub 4} undergoes easy dissolution in organic acid media at normal temperatures. However, dissolution of chromites and mixed ferrites is not that easy in organic chelant media at normal temperatures even in the presence of redox reagents. Hence, a high temperature process was attempted for the dissolution of ferrites and chromites. A re-circulation system consisting of an autoclave, pump, heat exchanger etc. all lined with teflon was used for carrying out high temperature dissolution experiments. This study describes the high temperature dissolution kinetics of Fe{sub 3}O{sub 4}, NiFe{sub 2}O{sub 4}, and Cr{sub 2}O{sub 3}. Nitrilotriacetic acid (NTA), a well known solvent for metal oxides, was applied at temperatures ranging from 80 to 180{sup o}C. About six fold increase in dissolution rate was observed for Fe{sub 3}O{sub 4} in this temperature range. Effect of N{sub 2}H{sub 4} on oxide dissolution was studied. Lower dissolution rates were observed for Fe{sub 3}O{sub 4} and NiFe{sub 2}O{sub 4} in the presence of hydrazine. Oxide dissolution efficiency of other chelating agents like EDTA, PDCA etc. and the effect of reducing agents like oxalic acid and ascorbic acid on high temperature dissolution also has been studied. The effect of incorporation of boron and zinc in the iron and chromium oxides has also been studied. Bonaccordite (Ni{sub 2}FeBO{sub 5}) has been observed in the fuel deposits of pressurized Water Reactors especially in the AOA affected plants. Zinc ferrite/chromite are formed in reactors adopting zinc injection passivation technique to control radiation field. Bonaccordite and zinc ferrite/chromite formed over the reactor coolant system structural materials are also difficult to dissolve

Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.

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Pinho, Antonio Ivanildo; Oliveira, Cláudia Sirlene; Lovato, Fabricio Luís; Waczuk, Emily Pansera; Piccoli, Bruna Candia; Boligon, Aline Augusti; Leite, Nadghia Figueredo; Coutinho, Henrique Douglas Melo; Posser, Thais; Da Rocha, João Batista Teixeira; Franco, Jeferson Luis

2017-01-01

Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.

Effects of pyrithiones and surfactants on zinc and enzyme levels in rabbits.

Science.gov (United States)

Spiker, R C; Ciuchta, H P

1980-04-01

The effects of zinc pyrithione (ZnPT) and sodium pyrithione (NaPT), including the influence of various vehicles, upon whole blood and plasma zinc levels and serum alkaline phosphatase (SAP) have been investigated in rabbits following dermal and/or iv administration. Two such vehicles, ammonium lauryl sulfate (ALS) and triethanolamine lauryl sulfate, affected zinc homeostasis differently than the pyrithiones, in that, unlike the pyrithiones, no whole blood changes were observed, although there were delayed and sustained declines in plasma zinc and SAP values. These changes were most likely related to the skin irritation caused by the surfactants. In contrast, NaPT-dimethyl sulfoxide (DMSO) dermal and iv exposures produced rapid decreases in plasma zinc followed by quick recovery, coupled with smaller and unsustained declines in SAP. Large increases in whole blood zinc were also observed in both cases, as well as in a ZnPT-DMSO iv exposure. DMSO itself had no effects on the measured parameters. Experiments involving combinations of the pyrithiones and ALS demonstrated effects on zinc homeostasis that were attributable to both substances, i.e. large increases in whole blood zinc (PT effect), quick drops in plasma zinc (PT effect) and slowly recovering plasma zinc and SAP values (surfactant effect). The chelating nature of the PT molecule may have been responsible for some of the observed changes in zinc distribution.

Direct current-induced electrogenerated chemiluminescence of hydrated and chelated Tb(III) at aluminum cathodes

International Nuclear Information System (INIS)

Hakansson, M.; Jiang, Q.; Spehar, A.-M.; Suomi, J.; Kotiranta, M.; Kulmala, S.

2005-01-01

Cathodic DC polarization of oxide-covered aluminum produces electrogenerated chemiluminescence from hydrated and chelated Tb(III) ions in aqueous electrolyte solutions. At the moment of cathodic voltage onset, a strong cathodic flash is observed, which is attributed to a tunnel emission of hot electrons into the aqueous electrolyte solution and the successive chemical reactions with the luminophores. However, within a few milliseconds the insulating oxide film is damaged and finally dissolved due to (i) indiffusion of protons or alkali metal ions into the thin oxide film, (ii) subsequent hydrogen evolution at the aluminum/oxide interface and (iii) alkalization of the electrode surface induced by hydrogen evolution reaction. When the alkalization of the electrode surface has proceeded sufficiently, chemiluminescence is generated with increasing intensity. Aluminum metal, short-lived Al(II), Al(I) or atomic hydrogen and its conjugated base form, hydrated electron, can act as highly reducing species in addition to the less energetic heterogeneously transferred electrons from the aluminum electrode. Tb(III) added as a hydrated ion in the solution probably luminesces in the form of Tb(OH) 3 or Tb(OH) 4 - by direct redox reactions of the central ion whereas multidentate aromatic ligand chelated Tb(III) probably luminesces by ligand sensitized chemiluminescence mechanism in which ligand is first excited by one-electron redox reactions, which is followed by intramolecular energy transfer to the central ion which finally emits light

Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.

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Shi, Fang; Sheng, Qin; Xu, Xinhua; Huang, Wenli; Kang, Y James

2015-09-01

Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation. © 2014 by the Society for Experimental Biology and Medicine.

Efficacy of a novel chelator BPCBG for removing uranium and protecting against uranium-induced renal cell damage in rats and HK-2 cells

Energy Technology Data Exchange (ETDEWEB)

Bao, Yizhong; Wang, Dan [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Li, Zhiming [Department of Chemistry, Fudan University, Shanghai 200433 (China); Hu, Yuxing; Xu, Aihong [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Wang, Quanrui [Department of Chemistry, Fudan University, Shanghai 200433 (China); Shao, Chunlin [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Chen, Honghong, E-mail: hhchen@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China)

2013-05-15

Chelation therapy is a known effective method to increase the excretion of U(VI) from the body. Until now, no any uranium chelator has been approved for emergency medical use worldwide. The present study aimed to evaluate the efficacy of new ligand BPCBG containing two catechol groups and two aminocarboxylic acid groups in decorporation of U(VI) and protection against acute U(VI) nephrotoxicity in rats, and further explored the detoxification mechanism of BPCBG for U(VI)-induced nephrotoxicity in HK-2 cells with comparison to DTPA-CaNa{sub 3}. Chelating agents were administered at various times before or after injections of U(VI) in rats. The U(VI) levels in urine, kidneys and femurs were measured 24 h after U(VI) injections. Histopathological changes in the kidney and serum urea and creatinine and urine protein were examined. After treatment of U(VI)-exposed HK-2 cells with chelating agent, the intracellular U(VI) contents, formation of micronuclei, lactate dehydrogenase (LDH) activity and production of reactive oxygen species (ROS) were assessed. It was found that prompt, advanced or delayed injections of BPCBG effectively increased 24 h-urinary U(VI) excretion and decreased the levels of U(VI) in kidney and bone. Meanwhile, BPCBG injection obviously reduced the severity of the U(VI)-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, urea and creatinine, and urine protein of U(VI) nephrotoxicity. In U(VI)-exposed HK-2 cells, immediate and delayed treatment with BPCBG significantly decreased the formation of micronuclei and LDH release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular ROS. Our data suggest that BPCBG is a novel bi-functional U(VI) decorporation agent with a better efficacy than DTPA-CaNa{sub 3}. - Highlights: ► BPCBG accelerated the urine U(VI) excretion and reduced the tissues U(VI) in rats. �

Chelation in metal intoxication

DEFF Research Database (Denmark)

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

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 incon......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...

Chelation Therapy for Mercury Poisoning

OpenAIRE

Rong Guan; Han Dai

2009-01-01

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

Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

Science.gov (United States)

Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

2018-02-12

There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since

Comparison of Three Analytical Methods for Separation of Mineral and Chelated Fraction from an Adulterated Zn-EDTA Fertilizer

International Nuclear Information System (INIS)

Khan, M.S.; Qazi, M.A.; Khan, N.A.; Mian, S.M.; Ahmed, N.; Ahmed, N.

2013-01-01

Summary: Different analytical procedures are being employed in the world to quantify the chelated portion in a Zn-EDTA fertilizer. Agriculture Department, Government of the Punjab is following Shahid's analytical method in this regard. This method is based on Ion-chromatography (IC) that separates the mineral zinc (Zn) from an adulterated Zn-EDTA fertilizer sample i.e. mixture of mineral and chelated Zn fractions. To find out its effectiveness and suitability, this comparative study was carried out by analyzing adulterated, non-adulterated Zn-EDTA standard and Zn-EDTA samples taken from market in thrice following three methods namely Shahid's (IC) analytical method, Atomic Absorption Spectrophotometric (AAS) method based on the principle of precipitating the mineral Zn fraction at high pH value by using alkali solution of suitable concentration and analysis of filtrate containing only chelated fraction and Association of Official Analytical Chemists (AOAC) method FM-841 respectively. Adulterated Zn-EDTA samples were prepared by mixing of known quantity of mineral Zn with chelated Zn-EDTA standard. The results showed that Shahid's analytical method and AAS method, both successfully estimated the chelated fraction. The AOAC FM-841 method was insensitive to put a ceiling on the mineral fraction hence did not furnish the reliable results. The Shahid's analytical method was selected being equallyeffective to produce reliable results both for solid and liquid Zn-EDTA samples. The AAS method was comparable in only liquid samples. (author)

Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

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Thiago B Kirsten

Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

Science.gov (United States)

Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

2008-02-22

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.

Science.gov (United States)

Wang, Shudong; Gu, Junlian; Xu, Zheng; Zhang, Zhiguo; Bai, Tao; Xu, Jianxiang; Cai, Jun; Barnes, Gregory; Liu, Qiu-Ju; Freedman, Jonathan H; Wang, Yonggang; Liu, Quan; Zheng, Yang; Cai, Lu

2017-06-01

Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Solution NMR characterization of Sgf73(1-104) indicates that Zn ion is required to stabilize zinc finger motif

International Nuclear Information System (INIS)

Lai, Chaohua; Wu, Minhao; Li, Pan; Shi, Chaowei; Tian, Changlin; Zang, Jianye

2010-01-01

Zinc finger motif contains a zinc ion coordinated by several conserved amino acid residues. Yeast Sgf73 protein was identified as a component of SAGA (Spt/Ada/Gcn5 acetyltransferase) multi-subunit complex and Sgf73 protein was known to contain two zinc finger motifs. Sgf73(1-104), containing the first zinc finger motif, was necessary to modulate the deubiquitinase activity of SAGA complex. Here, Sgf73(1-104) was over-expressed using bacterial expression system and purified for solution NMR (nuclear magnetic resonance) structural studies. Secondary structure and site-specific relaxation analysis of Sgf73(1-104) were achieved after solution NMR backbone assignment. Solution NMR and circular dichroism analysis of Sgf73(1-104) after zinc ion removal using chelation reagent EDTA (ethylene-diamine-tetraacetic acid) demonstrated that zinc ion was required to maintain stable conformation of the zinc finger motif.

Effect of zinc-lysine on growth, yield and cadmium uptake in wheat (Triticum aestivum L.) and health risk assessment.

Science.gov (United States)

Rizwan, Muhammad; Ali, Shafaqat; Hussain, Afzal; Ali, Qasim; Shakoor, Muhammad Bilal; Zia-Ur-Rehman, Muhammad; Farid, Mujahid; Asma, Maliha

2017-11-01

Cadmium (Cd) is among the most widespread toxic trace elements found in agricultural soils due to various anthropogenic activities. The role of micronutrient-amino chelates on reducing Cd toxicity in crop plants is recently introduced. The current study was conducted to highlight the role of foliar application of zinc-lysine (Zn-lys) complex on biochemical and growth parameters and Cd uptake in wheat (Triticum aestivum) grown in aged Cd-contaminated soil. Foliar concentration of Zn-lys (0, 10, 20, and 30 mg L -1 ) was applied at different time intervals (2nd, 3rd, 5th and 7th week of sowing) and plants were harvested at maturity. Folliar application of Zinc-lys significantly increased the photosynthesis, grain yield, enzyme activities and Zn contents in different plant tissues. Zinc-lys reduced Cd contents in grains, shoot and root as well as reduced the oxidative stress in wheat linearly in a dose-additive manner. Taken together, Zn-lys chelate efficiently improved wheat growth and fortified Zn contents while reduced Cd concentration in plant in a Zn-deficient Cd-contaminated soil. Although, health risk index (HRI) from the soil sampling area seems to be lower than <1 for Cd but may exceed due to long-term consumption of grains produced from such contaminated soil. Foliar applied Zn-lys reduced HRI which may help to reduce health risks associated with Cd. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

Science.gov (United States)

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Flame atomic absorption spectrometric determination of zinc, nickel, iron and lead in different matrixes after solid phase extraction on sodium dodecyl sulfate (SDS)-coated alumina as their bis (2-hydroxyacetophenone)-1, 3-propanediimine chelates

International Nuclear Information System (INIS)

Ghaedi, M.; Tavallali, H.; Shokrollahi, A.; Zahedi, M.; Montazerozohori, M.; Soylak, M.

2009-01-01

A sensitive and simple solid phase extraction method for the simultaneous determination of trace and toxic metals in food samples has been reported. The method is based on the adsorption of zinc, nickel, iron and lead on sodium dodecyl sulfate (SDS)-coated alumina, which is also chelated with bis (2-hydroxyacetophenone)-1, 3-propanediimine (BHAPN). The retained analyte ions on modified solid phase were eluted using 8 mL of 4 mol L -1 HNO 3 . The analyte determinations were carried out by flame atomic absorption spectrometry. The influences of some metal ions and anions on the recoveries of understudy analyte ions were investigated. The proposed method has been successfully applied for the evaluation of these trace and toxic metals in some traditional food samples from Iran.

Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

Science.gov (United States)

Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

2008-02-28

The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

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

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Athanasios Aessopos

2009-07-01

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

Effects of Zinc Compound on Body Weight and Recovery of Bone Marrow in Mice Treated with Total Body Irradiation

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Ming-Yii Huang

2007-09-01

Full Text Available This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI. ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract, and the control was reverse osmosis pure water (RO water. One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001. With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05. Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study

Zinc supplementation alleviates the progression of diabetic nephropathy by inhibiting the overexpression of oxidative-stress-mediated molecular markers in streptozotocin-induced experimental rats.

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Barman, Susmita; Pradeep, Seetur R; Srinivasan, Krishnapura

2018-04-01

Zinc deficiency during diabetes projects a role for zinc nutrition in the management of diabetic nephropathy. The current study explored whether zinc supplementation protects against diabetic nephropathy through modulation of kidney oxidative stress and stress-induced expression related to the inflammatory process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were exposed to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed a significant reversal of increased kidney weight and creatinine clearance. There was a significant reduction in hyperlipidemic condition along with improved PUFA:SFA ratio in the renal tissue. Expression of the lipid oxidative marker and expression of inflammatory markers, cytokines, fibrosis factors and apoptotic regulatory proteins observed in diabetic kidney were beneficially modulated by zinc supplementation, the ameliorative effect being concomitant with elevated antiapoptosis. There was a significant reduction in advanced glycation, expression of the receptor of the glycated products and oxidative stress markers. Zinc supplementation countered the higher activity and expression of polyol pathway enzymes in the kidney. Overexpression of the glucose transporters, as an adaptation to the increased need for glucose transport in diabetic condition, was minimized by zinc treatment. The pathological abnormalities in the renal architecture of diabetic animals were corrected by zinc intervention. Thus, dietary zinc supplementation has a significant beneficial effect in the control of diabetic nephropathy. This was exerted through a protective influence on oxidative-stress-induced cytokines, inflammatory proliferation and consequent renal injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

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Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

2008-10-01

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

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Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

2016-10-01

Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Beliefs about chelation among thalassemia patients

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Trachtenberg Felicia L

2012-12-01

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

Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation

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Lee, Eun-Jae; Lee, Hyejin; Huang, Tzyy-Nan; Chung, Changuk; Shin, Wangyong; Kim, Kyungdeok; Koh, Jae-Young; Hsueh, Yi-Ping; Kim, Eunjoon

2015-01-01

Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction. Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src. Clioquinol also improves social interaction in mice haploinsufficient for the transcription factor Tbr1, which accompanies NMDAR activation in the amygdala. These results suggest that trans-synaptic Zn mobilization induced by clioquinol rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR activation. PMID:25981743

Chelating polymeric membranes

KAUST Repository

Peinemann, Klaus-Viktor

2015-01-22

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

Article Commentary: Chelation Therapy for Mercury Poisoning

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Rong Guan

2009-01-01

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

Zinc Ameliorate Oxidative Stress and Hormonal Disturbance Induced by Methomyl, Abamectin, and Their Mixture in Male Rats

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Sameeh A. Mansour

2017-12-01

Full Text Available Exposure to mixtures of toxicants (e.g., pesticides is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET, abamectin (ABM, and their combination (MET+ABM, and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides. Additionally, one group received water only (control, and the other represented a positive zinc treatment. The obtained results revealed that MET was acutely more toxic than ABM. The tested pesticides induced significant elevation in lipid peroxidation and catalase levels, while declined the levels of the other tested parameters e.g., Superoxide dismutase (SOD, Glutathione-S-transferase (GST, Glutathione peroxidase (GPx, Glutathione reductase (GR, Cytochrome P450 (CYP450, testosterone, and thyroxine. Biochemical alterations induced by the mixture were greater than those recorded for each of the individual insecticides. The joint action analysis, based on the obtained biochemical data, revealed the dominance of antagonistic action among MET and ABM. Zinc supplementation achieved noticeable ameliorative effects. It was concluded that zinc may act as a powerful antioxidant, especially in individuals who are occupationally exposed daily to low doses of such pesticides.

Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

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Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

2016-07-01

Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.

Evolutionary analysis of a novel zinc ribbon in the N-terminal region of threonine synthase.

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Kaur, Gurmeet; Subramanian, Srikrishna

2017-10-18

Threonine synthase (TS) catalyzes the terminal reaction in the biosynthetic pathway of threonine and requires pyridoxal phosphate as a cofactor. TSs share a common catalytic domain with other fold type II PALP dependent enzymes. TSs are broadly grouped into two classes based on their sequence, quaternary structure, and enzyme regulation. We report the presence of a novel zinc ribbon domain in the N-terminal region preceding the catalytic core in TS. The zinc ribbon domain is present in TSs belonging to both classes. Our sequence analysis reveals that archaeal TSs possess all zinc chelating residues to bind a metal ion that are lacking in the structurally characterized homologs. Phylogenetic analysis suggests that TSs with an N-terminal zinc ribbon likely represents the ancestral state of the enzyme while TSs without a zinc ribbon must have diverged later in specific lineages. The zinc ribbon and its N- and C-terminal extensions are important for enzyme stability, activity and regulation. It is likely that the zinc ribbon domain is involved in higher order oligomerization or mediating interactions with other biomolecules leading to formation of larger metabolic complexes.

Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

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Elizabeth J Polvi

2016-10-01

Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

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Bo Young Choi

2017-01-01

Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

Lead induced dyslipidemia: The comparative effects of ascorbate ...

African Journals Online (AJOL)

R.N. UGBAJA

2013-04-10

Apr 10, 2013 ... Key words: Ascorbate, chelating agents, dyslipidemia, lead exposure, plumbism. .... elements like iron, zinc, calcium and a host of other divalent elements in ..... cholesterol synthesis and transport pathways may be adversely ...

The protective role of Gamma-Tocopherol and zinc cysteine against oxidative stress induced by gamma irradiation in albino rats

International Nuclear Information System (INIS)

Anis, L.M.

2004-01-01

The present study aimed to evaluate the capability of α tocopherol (naturally occurring antioxidant) and zinc cysteine against radiation induced oxidative stress. α Tocopherol was dissolved in corn oil and g, to the animals for ten successive days at a dose of 20 mg/kg b weight/day. Zinc cysteine was delivered to rats via intraperitoneal inject at a concentration of 25 mg/kg body weight/day for two successive days, rats were exposed to whole body gamma irradiation at a dose level of Gy. The activities of super oxide dismutase (SOD) and catalase and also concentrations of reduced glutathione (GSH) and malonaldehyde (Mi . were determined in the blood. The levels of metallothionein, zinc and copper were estimated in the serum, liver and kidney of the tested animals. The obtained results revealed that administration of a-tocopherol and zinc cysteine before gamma radiation exposure diminish significantly the decrease in blood SOD and catalase activities as compared to untreated irradiated rats. Also, the decrease in blood GSH concentration was less manifested and the decrease in the level of MDA was significant. The pre-gamma irradiation administration of zinc cysteine induced significant changes in the levels of metallothionein compared to both a-tocopherol supplemented and gamma irradiated rat groups. The amelioration occurred in the levels of zinc and copper postulated the positive role of vitamin E and zinc cysteine in alleviating all the levels of these elements

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate.

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Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min; Chung, Tae Nyoung; Suh, Sang Won

2018-01-01

Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30  μ M and 100  μ M of ZnCl 2 . Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate

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Mi-Young Moon

2018-01-01

Full Text Available Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30 μM and 100 μM of ZnCl2. Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

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Anjali Kumari

Full Text Available Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl ethylenediamine (TPEN and Zinc Sulfate (ZnSO4. Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death

Effects of synthetic Zn chelates on flax response and soil Zn status

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, D.; Almendros, P.; Alvarez, J.M.

2016-11-01

Throughout the world, flax (Linum usitatissimum L.) is often grown in Zn-deficient soils, but appropriate fertilizer management can optimize both crop yield and micronutrient content. A greenhouse experiment was conducted on Typic Haploxeralf (pH 6.1) and Typic Calcixerept (pH 8.1) soils to study the relative efficiency of chelated Zn using two application rates of three different Zn sources [Zn-EDDHSA, ethylenediamine-di-(2-hydroxy-5-sulfophenylacetate of Zn); Zn-HEDTA, N-2-hydroxyethyl-ethylenediaminetriacetate of Zn; and Zn-EDTA, ethylenediaminetetraacetate of Zn]. Dry matter /DM) yield, Zn concentration, chlorophyll content, crude fiber and tensile properties were monitored and the soil-Zn status (available-Zn, Zn-fractions and total-Zn) was assessed. Zinc chelate applications increased the most labile forms of Zn in soils and Zn concentrations in plants. The low rate of Zn generally had a beneficial effect on DM yield and tensile properties. The exception was Zn-EDTA in the weakly acidic soil, where the highest Zn concentrations were observed in leaves and whole shoots; this coincided with the largest concentrations of labile Zn in soil. The most efficient fertilizers were Zn-EDDHSA (in both soils) and Zn-EDTA (in the calcareous soil). The relatively large amounts of labile and available Zn present in both of the soils fertilized with Zn-EDTA points to the applying this chelate at lower rate than 5 mg Zn/kg; this should, in turn, reduce the cost of Zn fertilization and minimize environmental pollution risk. (Author)

Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

DEFF Research Database (Denmark)

Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

2001-01-01

, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs......, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All......The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured...

Zinc release in the lateral nucleus of the amygdala by stimulation of the entorhinal cortex.

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Takeda, Atsushi; Imano, Sachie; Itoh, Hiromasa; Oku, Naoto

2006-11-06

Zinc release in the lateral nucleus of the amygdala was examined using rat brain slices. The lateral and basolateral nuclei in the amygdala were evidently stained by Timm's sulfide-silver staining method. When the amygdala including both the nuclei was stimulated with 100 mM KCl by means of in vivo microdialysis, extracellular zinc concentration was increased significantly. Zinc release in the lateral nucleus of the amygdala innervated by the entorhinal cortex was next examined in brain slices double-stained with zinc and calcium indicators. Extracellular zinc signal (ZnAF-2) in the lateral nucleus was increased with intracellular calcium signal (calcium orange) during delivery of tetanic stimuli to the entorhinal cortex. Both the increases were completely inhibited by addition of 1 micro M tetrodotoxin, a sodium channel blocker. Furthermore, calcium signal in the lateral nucleus during delivery of tetanic stimuli to the entorhinal cortex was increased in the presence of 10 micro M CNQX, an AMPA/KA receptor antagonist, and this increase was facilitated by addition of 1 mM CaEDTA, a membrane-impermeable zinc chelator. The present study suggested that zinc is released in the lateral nucleus of the amygdala by depolarization of the entorhinal neurons. In the lateral nucleus, zinc released may suppress the increase in presynaptic calcium signal.

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

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Atsushi Takeda

Full Text Available We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ concentration. A single injection of Aβ (25 pmol into the dentate gyrus affected dentate gyrus long-term potentiation (LTP 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

Science.gov (United States)

Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

2014-01-01

We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy.

Science.gov (United States)

Timofeeva, Olga; Nadler, J Victor

2006-03-17

Recurrent mossy fiber synapses in the dentate gyrus of epileptic brain facilitate the synchronous firing of granule cells and may promote seizure propagation. Mossy fiber terminals contain and release zinc. Released zinc inhibits the activation of NMDA receptors and may therefore oppose the development of granule cell epileptiform activity. Hippocampal slices from rats that had experienced pilocarpine-induced status epilepticus and developed a recurrent mossy fiber pathway were used to investigate this possibility. Actions of released zinc were inferred from the effects of chelation with 1 mM calcium disodium EDTA (CaEDTA). When granule cell population bursts were evoked by mossy fiber stimulation in the presence of 6 mM K(+) and 30 microM bicuculline, CaEDTA slowed the rate at which evoked bursting developed, but did not change the magnitude of the bursts once they had developed fully. The effects of CaEDTA were then studied on the pharmacologically isolated NMDA receptor- and AMPA/kainate receptor-mediated components of the fully developed bursts. CaEDTA increased the magnitude of NMDA receptor-mediated bursts and reduced the magnitude of AMPA/kainate receptor-mediated bursts. CaEDTA did not affect the granule cell bursts evoked in slices from untreated rats by stimulating the perforant path in the presence of bicuculline and 6 mM K(+). These results suggest that zinc released from the recurrent mossy fibers serves mainly to facilitate the recruitment of dentate granule cells into population bursts.

Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.

Science.gov (United States)

Isaev, Nickolay K; Genrikhs, Elisaveta E; Aleksandrova, Olga P; Zelenova, Elena A; Stelmashook, Elena V

2016-05-27

Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of natural organic acids and synthetic chelates at enhancing phytoextraction of metals from a multi-metal contaminated soil

International Nuclear Information System (INIS)

Clistenes do Nascimento, Williams A.; Amarasiriwardena, Dula; Xing, Baoshan

2006-01-01

Chemically assisted phytoremediation has been developing to induce accumulation of metals by high biomass plants. Synthetic chelates have shown high effectiveness to reach such a goal, but they pose serious drawbacks in field application due to the excessive amount of metals solubilized. We compared the performance of synthetic chelates with naturally occurring low molecular weight organic acids (LMWOA) in enhancing phytoextraction of metals by Indian mustard (Brassica juncea) from multi-metal contaminated soils. Gallic and citric acids were able to induce removal of Cd, Zn, Cu, and Ni from soil without increasing the leaching risk. Net removal of these metals caused by LMWOA can be as much as synthetic chelates. A major reason for this is the lower phytotoxicity of LMWOA. Furthermore, supplying appropriate mineral nutrients increased biomass and metal removal. - Organic acids can be as efficient as synthetic chelates for use in phytoextraction of multi-metal contaminated soils

PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.

Science.gov (United States)

Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun

2017-10-01

Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration.

Directory of Open Access Journals (Sweden)

M Indriati Hood

Full Text Available Acinetobacter baumannii is an important nosocomial pathogen that accounts for up to 20 percent of infections in intensive care units worldwide. Furthermore, A. baumannii strains have emerged that are resistant to all available antimicrobials. These facts highlight the dire need for new therapeutic strategies to combat this growing public health threat. Given the critical role for transition metals at the pathogen-host interface, interrogating the role for these metals in A. baumannii physiology and pathogenesis could elucidate novel therapeutic strategies. Toward this end, the role for calprotectin- (CP-mediated chelation of manganese (Mn and zinc (Zn in defense against A. baumannii was investigated. These experiments revealed that CP inhibits A. baumannii growth in vitro through chelation of Mn and Zn. Consistent with these in vitro data, Imaging Mass Spectrometry revealed that CP accompanies neutrophil recruitment to the lung and accumulates at foci of infection in a murine model of A. baumannii pneumonia. CP contributes to host survival and control of bacterial replication in the lung and limits dissemination to secondary sites. Using CP as a probe identified an A. baumannii Zn acquisition system that contributes to Zn uptake, enabling this organism to resist CP-mediated metal chelation, which enhances pathogenesis. Moreover, evidence is provided that Zn uptake across the outer membrane is an energy-dependent process in A. baumannii. Finally, it is shown that Zn limitation reverses carbapenem resistance in multidrug resistant A. baumannii underscoring the clinical relevance of these findings. Taken together, these data establish Zn acquisition systems as viable therapeutic targets to combat multidrug resistant A. baumannii infections.

Compartmentation of metals in foliage of Populus tremula grown on soils with mixed contamination. II. Zinc binding inside leaf cell organelles

Energy Technology Data Exchange (ETDEWEB)

Vollenweider, Pierre, E-mail: pierre.vollenweider@wsl.c [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland); Bernasconi, Petra [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland); Environmental Protection Office (AfU), Aabachstrasse 5, 6300 Zug (Switzerland); Gautschi, Hans-Peter [Centre for Microscopy and Image Analysis (CMI), University of Zurich, Gloriastrasse 30, 8006 Zuerich (Switzerland); Menard, Terry; Frey, Beat; Guenthardt-Goerg, Madeleine S. [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland)

2011-01-15

The phytoextraction potential of plants for removing heavy metals from polluted soils is determined by their capacity to store contaminants in aboveground organs and complex them safely. In this study, the metal compartmentation, elemental composition of zinc deposits and zinc complexation within leaves from poplars grown on soil with mixed metal contamination was analysed combining several histochemical and microanalytical approaches. Zinc was the only heavy metal detected and was stored in several organelles in the form of globoid deposits showing {beta}-metachromasy. It was associated to oxygen anions and different cations, noteworthy phosphorous. The deposit structure, elemental composition and element ratios indicated that zinc was chelated by phytic acid ligands. Maturation processes in vacuolar vs. cytoplasmic deposits were suggested by differences in size and amounts of complexed zinc. Hence, zinc complexation by phytate contributed to metal detoxification and accumulation in foliage but could not prevent toxicity reactions therein. - Zinc contaminants translocated to symplast of aged leaves were detoxified by phytic acid ligands.

Compartmentation of metals in foliage of Populus tremula grown on soils with mixed contamination. II. Zinc binding inside leaf cell organelles

International Nuclear Information System (INIS)

Vollenweider, Pierre; Bernasconi, Petra; Gautschi, Hans-Peter; Menard, Terry; Frey, Beat; Guenthardt-Goerg, Madeleine S.

2011-01-01

The phytoextraction potential of plants for removing heavy metals from polluted soils is determined by their capacity to store contaminants in aboveground organs and complex them safely. In this study, the metal compartmentation, elemental composition of zinc deposits and zinc complexation within leaves from poplars grown on soil with mixed metal contamination was analysed combining several histochemical and microanalytical approaches. Zinc was the only heavy metal detected and was stored in several organelles in the form of globoid deposits showing β-metachromasy. It was associated to oxygen anions and different cations, noteworthy phosphorous. The deposit structure, elemental composition and element ratios indicated that zinc was chelated by phytic acid ligands. Maturation processes in vacuolar vs. cytoplasmic deposits were suggested by differences in size and amounts of complexed zinc. Hence, zinc complexation by phytate contributed to metal detoxification and accumulation in foliage but could not prevent toxicity reactions therein. - Zinc contaminants translocated to symplast of aged leaves were detoxified by phytic acid ligands.

Radiation induced traps of zinc phosphate and phosphide

International Nuclear Information System (INIS)

Murali, K.R.; Rao, D.R.

1980-01-01

Thermoluminescence (TL) glow curve (TGC) method has been used to study the traps produced by X-irradiation in Zn 3 (PO 4 ) 2 and Zn 3 P 2 . Prominent TL glow peaks were observed at 100 0 and 360 0 C for zinc phosphate while for zinc phosphide only one glow peak at 245 0 C was observed, and in the latter case the TL output was in general quite low compared to zinc phosphate. The TL spectra for both the glow peaks of zinc phosphate indicated emission band in the region around 560 nm, while for zinc phosphide the emission occurred at 575 nm (in the temperature region 200-270 0 C). The low temperature glow peaks below 270 0 C were less stable compared to those above 300 0 C and were completely destroyed when the irradiated samples were stored in darkness for 24 hr at room temperature. Shining by 470 nm light however produced preferential bleaching of the two TL peaks at 100 and 360 0 C with no effect on the 245 0 C glow peak of zinc phosphide. It is concluded that during heat treatment large numbers of Zn-vacancies are formed due to which complexes like Zn-P are produced by irradiation and the TL traps destroyed in a radiative recombination process are related with these complexes. (author)

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

Science.gov (United States)

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

2008-05-01

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

Chitosan-functionalized gold nanoparticles for colorimetric detection of mercury ions based on chelation-induced aggregation

International Nuclear Information System (INIS)

Chen, Zhengbo; Zhang, Chenmeng; Tan, Yuan; Zhou, Tianhui; Ma, He; Wan, Chongqing; Lin, Yuqing; Li, Kai

2015-01-01

We are presenting a colorimetric assay for mercury (II) ions. It is based on citosan-functionalized gold nanoparticles (AuNPs) that act as a signaling probe. Hg (II) induces the aggregation of the chitosan-AuNPs through a chelation reaction that occurs between chitosan and Hg (II). This results in a strong decrease of the absorbance of the modified AuNPs and a color change from red to blue. This sensing system displays excellent selectivity over other metal ions and a detection limit as low as 1.35 μM which is lower than the allowed level of Hg (II) in drinking water (30 μM) as defined by World Health Organization. The method is inexpensive, facile, sensitive, and does not require the addition of other reagents in order to improving sensitivity. (author)

Manganese(II) chelate contrast media

International Nuclear Information System (INIS)

Rocklage, S.M.; Quay, S.C.

1994-01-01

New chelate forming compounds for use as contrast media in NMR imaging are described. Especially mentioned are manganese(II) ion chelates of N,N' dipyridoxaldiamine, N,N' diacetic acid, and salts and esters thereof. 1 fig

Physiologic actions of zinc related to inhibition of acid and alkali production by oral streptococci in suspensions and biofilms.

Science.gov (United States)

Phan, T-N; Buckner, T; Sheng, J; Baldeck, J D; Marquis, R E

2004-02-01

Zinc is a known inhibitor of acid production by mutans streptococci. Our primary objective was to extend current knowledge of the physiologic bases for this inhibition and also for zinc inhibition of alkali production by Streptococcus rattus FA-1 and Streptococcus salivarius ATCC 13419. Zinc at concentrations as low as 0.01-0.1 mm not only inhibited acid production by cells of Streptococcus mutans GS-5 in suspensions or in biofilms but also sensitized glycolysis by intact cells to acidification. Zinc reversibly inhibited the F-ATPase of permeabilized cells of S. mutans with a 50% inhibitory concentration of about 1 mm for cells in suspensions. Zinc reversibly inhibited the phosphoenolpyruvate: sugar phosphotransferase system with 50% inhibition at about 0.3 mm ZnSO4, or about half that concentration when the zinc-citrate chelate was used. The reversibility of these inhibitory actions of zinc correlates with findings that it is mainly bacteriostatic rather than bactericidal. Zinc inhibited alkali production from arginine or urea and was a potent enzyme inhibitor for arginine deiminase of S. rattus FA-1 and for urease of S. salivarius. In addition, zinc citrate at high levels of 10-20 mm was weakly bactericidal.

Novel mechanism of aberrant ZIP4 expression with zinc supplementation in oral tumorigenesis

International Nuclear Information System (INIS)

Ishida, Sho; Kasamatsu, Atsushi; Endo-Sakamoto, Yosuke; Nakashima, Dai; Koide, Nao; Takahara, Toshikazu; Shimizu, Toshihiro; Iyoda, Manabu; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2017-01-01

Zrt-Irt-like protein 4 (ZIP4) is critical molecule for proper mammalian development and releasing zinc from vesicular compartments. Recent studies suggested that ZIP4 plays an important role of tumor progression in pancreatic, prostate, and hepatocellular cancers, however, little is known about the detail mechanism of ZIP4 in their cancers. In the present study, we examined the possibility of ZIP4 as a new molecular target for oral squamous cell carcinoma (OSCC). We evaluated ZIP4 expression in OSCC-derived cell lines and primary OSCC samples by quantitative RT-PCR, immunoblotting, and immunohistochemistry (IHC). We also analyzed the clinical correlation between ZIP4 status and clinical behaviors in patients with OSCC. In addition, ZIP4 knockdown cells (shZIP4 cells) and ZnCl 2 treatment were used for functional experiments, including cellular proliferation assay, zinc uptake assay, and cell-cycle analysis. ZIP4 mRNA and protein were up-regulated significantly in OSCCs compared with normal counterparts in vitro and in vivo. IHC showed that ZIP4 expression in the primary OSCC was positively correlated with primary tumoral size. The shZIP4 cells showed decrease accumulation of intercellular zinc and decreased cellular growth by cell-cycle arrest at the G1 phase, resulting from up-regulation of cyclin-dependent kinase inhibitors and down-regulation of cyclins and cyclin-dependent kinases. Since cellular growth of OSCC cells after treatment with zinc was significantly greater than control cells, we speculated that intercellular ZnCl 2 accumulation is an important factor for cellular growth. Consistent with our hypothesis, not only decreased zinc uptake by ZIP4 knockdown but also chelating agent, N,N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), showed inhibitory effects of cellular proliferation. Therefore, our data provide evidence for an essential role of ZIP4 and intracellular zinc for tumoral growth in OSCC, suggesting that zinc uptake might be a

Decomposition rates of radiopharmaceutical indium chelates in serum

International Nuclear Information System (INIS)

Yeh, S.M.; Meares, C.F.; Goodwin, D.A.

1979-01-01

The rates at which six small aminopolycarboxylate chelates of trivalent 111 In and three protein-bound chelates of 111 In deliver indium to the serum protein transferrin have been studied in sterile human serum at pH 7.3, 37 deg C. Sterically hindered chelates containing a substituent on an ethylene carbon of EDTA decompose with rates in the range 0.03 to 0.11% per day - one to two orders of magnitude slower than other chelates. Only small differences are observed between rates of decomposition for low-molecular-weight chelates and for protein-bound chelates having analogous structures. (author)

Fluid extraction using carbon dioxide and organophosphorus chelating agents

Science.gov (United States)

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.

The experimental study on protective effects and mechanisms of chelating agents of catechols amino carboxylic acid for radiation injury induced by actimides(Th-234)

International Nuclear Information System (INIS)

Chen, H. H.; Luo, M. C.; Sun, M. Z.; Hu, Y. X.; Wang, Y. H.; Jin, M. Y.; Cheng, W. Y.

2002-01-01

The decorporative efficacy and antioxidative action of prompt and delayed consecutive administration of catecholicpolyaminopolycarboxylate ligands, 7601 and 9501 for radiothorium in mice were investigated. DTPA and Vitamin E were used as positive controls. The competitive abilities of 7601 and 9501 to mobilize the thorium with BSA were studied. Their inhibition effects on superoxide anionas radicals were measured with electron spin resonance. The results showed that 7601 and 9501 are able to effectively prevent the internal radiation injury induced radiothorium, attributing to their double functions of pronounced removal effectiveness and antioxidative action. Their protective effects were better than DTPA and Vitamin E. The mechanisms of protective effects of 7601 and 9501 for internal radiation injury was close related to competitive ability of chelating agent to chelate the thorium with BSA and oxygen free radical scavenging activities

Influence of soil zinc concentrations on zinc sensitivity and functional diversity of microbial communities

International Nuclear Information System (INIS)

Lock, K.; Janssen, C.R.

2005-01-01

Pollution induced community tolerance (PICT) is based on the phenomenon that toxic effects reduce survival of the most sensitive organisms, thus increasing community tolerance. Community tolerance for a contaminant is thus a strong indicator for the presence of that contaminant at the level of adverse concentrations. Here we assessed PICT in 11 soils contaminated with zinc runoff from galvanised electricity pylons and 11 reference soils sampled at 10 m distance from these pylons. Using PICT, the influence of background concentration and bioavailability of zinc on zinc sensitivity and functional diversity of microbial communities was assessed. Zinc sensitivity of microbial communities decreased significantly with increasing zinc concentrations in pore water and calcium chloride extracted fraction while no significant relationship was found with total zinc concentration in the soil. It was also found that functional diversity of microbial communities decreased with increasing zinc concentrations, indicating that increased tolerance is indeed an undesirable phenomenon when environmental quality is considered. The hypothesis that zinc sensitivity of microbial communities is related to background zinc concentration in pore water could not be confirmed. - Zinc sensitivity of microbial communities and functional diversity decrease with increasing zinc concentration in the pore water

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

Energy Technology Data Exchange (ETDEWEB)

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.

Zinc-induced protection against cadmium

Energy Technology Data Exchange (ETDEWEB)

Early, J.L.; Schnell, R.C.

1978-02-01

Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

Influence of Formulation on the Cuticular Penetration and on Spray Deposit Properties of Manganese and Zinc Foliar Fertilizers

Directory of Open Access Journals (Sweden)

Alvin Alexander

2016-06-01

Full Text Available Foliar fertilization, or the application of nutrient solutions to the foliage of plants, has become a very important tool as a supplement to traditional soil fertilization. So far, knowledge about the real mechanisms of foliar nutrient uptake is still limited. In this study different manganese (Mn and zinc (Zn carriers differing in their solubility and chemical characteristics (chelated or non-chelated, with or without the presence of a surfactant-penetrant were compared with regard to their penetration characteristics through enzymatically-isolated cuticles. The experiments were explicitly conducted under high humidity conditions in order not to penalize compounds with a higher deliquescent point. The results show that Mn penetrates more rapidly through the cuticle than Zn ions for unknown reasons. The addition of a surfactant-penetrant enhances the penetration rate in the case of Mn ions. This trend is much less pronounced for zinc ions. Formulations based on insoluble carriers, such as carbonate or oxide, only poorly penetrate through the cuticle. In order to rapidly control micronutrient deficiency problems, only fully water soluble micronutrient carriers should be used.

Compartmentation of metals in foliage of Populus tremula grown on soils with mixed contamination. II. Zinc binding inside leaf cell organelles.

Science.gov (United States)

Vollenweider, Pierre; Bernasconi, Petra; Gautschi, Hans-Peter; Menard, Terry; Frey, Beat; Günthardt-Goerg, Madeleine S

2011-01-01

The phytoextraction potential of plants for removing heavy metals from polluted soils is determined by their capacity to store contaminants in aboveground organs and complex them safely. In this study, the metal compartmentation, elemental composition of zinc deposits and zinc complexation within leaves from poplars grown on soil with mixed metal contamination was analysed combining several histochemical and microanalytical approaches. Zinc was the only heavy metal detected and was stored in several organelles in the form of globoid deposits showing β-metachromasy. It was associated to oxygen anions and different cations, noteworthy phosphorous. The deposit structure, elemental composition and element ratios indicated that zinc was chelated by phytic acid ligands. Maturation processes in vacuolar vs. cytoplasmic deposits were suggested by differences in size and amounts of complexed zinc. Hence, zinc complexation by phytate contributed to metal detoxification and accumulation in foliage but could not prevent toxicity reactions therein. Copyright © 2010 Elsevier Ltd. All rights reserved.

The beneficial effects of zinc on diabetes-induced kidney damage in murine rodent model of type 1 diabetes mellitus.

Science.gov (United States)

Yang, Fan; Li, Bing; Dong, Xiaoming; Cui, Wenpeng; Luo, Ping

2017-07-01

Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3β phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN. Copyright © 2017 Elsevier GmbH. All rights reserved.

Direct in situ measurement of dissolved zinc in the presence of zinc oxide nanoparticles using anodic stripping voltammetry.

Science.gov (United States)

Jiang, Chuanjia; Hsu-Kim, Heileen

2014-11-01

The wide use of metal-based nanomaterials such as zinc oxide (ZnO) nanoparticles (NPs) has generated concerns regarding their environmental and health risks. For ZnO NPs, their toxicity in aquatic systems often depends on the release of dissolved zinc species, and the rate of dissolution is influenced by water chemistry, including the presence of zinc-chelating ligands. A challenge, however, remains in quantifying the dissolution of ZnO NPs, particularly for time scales that are short enough to determine rates. This paper reports the application of anodic stripping voltammetry (ASV) with a hanging mercury drop electrode to directly measure the concentration of dissolved zinc in ZnO NP suspensions, without separation of the ZnO NPs from the aqueous phase. The effects of the deposition time and the electrochemical potential scan rate on the ASV measurement were consistent with expectations for dissolved phase measurements. The dissolved zinc concentration measured by ASV ([Zn]ASV) was compared with that measured by inductively coupled plasma mass spectrometry (ICP-MS) after ultracentrifugation ([Zn]ICP-MS), for four types of ZnO NPs with different coatings and primary particle diameters. For small ZnO NPs (4-5 nm), [Zn]ASV was 20% higher than [Zn]ICP-MS, suggesting that these small NPs contributed to the voltammetric measurement. For larger ZnO NPs (approximately 20 nm), [Zn]ASV was (79 ± 19)% of [Zn]ICP-MS, despite the high concentrations of ZnO NPs in suspension. Using ASV, the dissolution of ZnO NPs was studied, with or without Suwannee River Fulvic Acid (SRFA). Although SRFA diminished the ASV stripping current, dissolution of 20 nm ZnO NPs was significantly promoted at high fulvic acid to ZnO NP ratios. The ASV method described in this paper provides a useful tool for studying the dissolution kinetics of ZnO NPs in complex environmental matrices.

Lisina digestível e zinco quelado para frangos de corte machos: desempenho e retenção de nitrogênio na fase pré-inicial Digestible lysine and zinc chelate to male broiler: Performance in the pre-initial phase and nitrogen retention

Directory of Open Access Journals (Sweden)

Lilian Bernadete Namazu

2008-09-01

Full Text Available Em dois ensaios experimentais, avaliaram-se níveis de lisina digestível (0,90; 1,00; 1,10; 1,20 e 1,40% combinados a zinco quelado (43 e 253 ppm para frangos de corte machos. Os períodos considerados foram: 1 a 11 dias de idade (desempenho e 1 a 7 dias de idade (balanço de nitrogênio. O delineamento experimental utilizado foi de blocos ao acaso, em esquema fatorial 5 × 2. No ensaio de desempenho, utilizaram-se 7 repetições e 15 aves por unidade experimental e, no ensaio de digestibilidade, 6 repetições e 6 aves por unidade experimental. As dietas continham 2.960 de EM/kg e 21% de proteína bruta. Na fase de 1 a 11 dias de idade, não houve efeito de interação lisina digestível × zinco quelado no desempenho, mas verificou-se efeito quadrático dos níveis de lisina digestível sobre o peso final, o ganho de peso e o ganho de peso relativo e efeito linear crescente no consumo de ração. A conversão alimentar não diferiu com as variações dos níveis de lisina digestível e zinco na dieta. Nas condições de avaliação do desempenho, o nível ótimo de lisina digestível para frangos de corte machos mantidos em piso de concreto é de 1,19%. Na fase de 1 a 7 dias de idade, não houve influência da relação entre níveis de lisina digestível e zinco quelado no balanço de nitrogênio. A retenção de nitrogênio aumentou de forma linear crescente com o aumento da concentração de lisina digestível na dieta, o que está de acordo com o aumento linear do ganho de peso e da eficiência alimentar. A exigência de lisina digestível para frangos de corte machos de 1 a 7 dias de idade é igual ou superior a 1,40%.Two experiments were carried out to evaluate different levels of digestible lysine (0.90; 1.00; 1.10; 1.20; e 1.40% combined with zinc chelate (43 and 253 ppm to male broiler. The considered periods were: initial phase - performance (1 to 11 days old and nitrogen retention (1 to 7 days old. A randomized block experimental

Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

Science.gov (United States)

Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert

2014-10-01

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. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children 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 deferoxamine (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 quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of Antioxidant Active Packaging.

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Lin, Zhuangsheng; Goddard, Julie

2018-02-01

Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA) are widely used as additives to control trace transition metal induced oxidation in consumer products. To enable removal of synthetic chelators in response to increasing consumer demand for clean label products, metal-chelating active food packaging technologies have been developed with demonstrated antioxidant efficacy in simulated food systems. However, prior work in fabrication of metal-chelating materials leveraged batch chemical reactions to tether metal-chelating ligands, a process with limited industrial translatability for large-scale fabrication. To improve the industrial translatability, we have designed a 2-step laminated photo-grafting process to introduce metal chelating functionality onto common polymeric packaging materials. Iminodiacetic acid (IDA) functionalized materials were fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films, followed by a second photo-grafting process to graft-polymerize an IDA functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under atmospheric conditions and was completed in 2 min. The resulting IDA functionalized metal-chelating material was able to chelate iron and copper, and showed antioxidant efficacy against ascorbic acid degradation, supporting its potential to be used synergistically with natural antioxidants for preservation of food and beverage products. The 2-step photo-grafting process improves the throughput of active packaging coatings, enabling potential roll-to-roll fabrication of metal-chelating active packaging materials for antioxidant food packaging applications. To address consumer and retail demands for "clean label" foods and beverages without a corresponding loss in product quality and shelf life, producers are seeking next generation technologies such as active packaging. In this work, we will report the synthesis of metal-chelating active packaging films, which enable removal

Use of radioactive tracers in chemical reactions. the displacement of zinc-nickel complexes with quantitative determination of nickel

International Nuclear Information System (INIS)

Mazzilli, B.; Saiki, M.

1983-01-01

The present paper presents a method for the determination of small quantities of nickel radioactive tracers. An analytical application of the displacement reaction between nickel and zinc ethylenediaminetetraacetate labeled with zinc-65 is pursued. This method is based on the extraction of radioactive zinc displaced by nickel from the zinc chelate into a dithizone-carbon tetrachloride solution and the subsequent measurement of the activity of an aliquot of the extract. The method is very sensitive and nickel can be measured in concentrations as small as 0.1 μg/ml or even less, depending on the specific activity of the radioreagent used. The precision and the accuracy of the method are determined. The problem of interferences is also investigated and an attempt is made in order to eliminate them by using masking agents or by means of a previous separation between nickel and other interfering metals. (Author) [pt

Radiation induced structural changes in alpha-copper-zinc alloys

International Nuclear Information System (INIS)

Schuele, W.; Gieb, M.

1991-01-01

During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

Solubilization of insoluble zinc compounds by Gluconacetobacter diazotrophicus and the detrimental action of zinc ion (Zn2+) and zinc chelates on root knot nematode Meloidogyne incognita.

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Saravanan, V S; Kalaiarasan, P; Madhaiyan, M; Thangaraju, M

2007-03-01

To examine the zinc (Zn) solubilization potential and nematicidal properties of Gluconacetobacter diazotrophicus. Atomic Absorption Spectrophotometer, Differential Pulse Polarography and Gas Chromatography Coupled Mass Spectrometry were used to estimate the total Zn and Zn(2+) ions and identify the organic acids present in the culture supernatants. The effect of culture filtrate of Zn-amended G. diazotrophicus PAl5 on Meloidogyne incognita in tomato was examined under gnotobiotic conditions. Gluconacetobacter diazotrophicus PAl5 effectively solubilized the Zn compounds tested and 5-ketogluconic acid was identified as the major organic acid aiding the solubilization of zinc oxide. The presence of Zn compounds in the culture filtrates of G. diazotrophicus enhanced the mortality and reduced the root penetration of M. incognita under in vitro conditions. 5-ketogluconic acid produced by G. diazotrophicus mediated the solubilization process and the available Zn(2+) ions enhanced the nematicidal activity of G. diazotrophicus against M. incognita. Zn solubilization and enhanced nematicidal activity of Zn-amended G. diazotrophicus provides the possibility of exploiting it as a plant growth promoting bacteria.

Iron overload and chelation therapy in myelodysplastic syndromes.

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Temraz, Sally; Santini, Valeria; Musallam, Khaled; Taher, Ali

2014-07-01

Iron overload remains a concern in MDS patients especially those requiring recurrent blood transfusions. The consequence of iron overload may be more relevant in patients with low and intermediate-1 risk MDS who may survive long enough to experience such manifestations. It is a matter of debate whether this overload has time to yield organ damage, but it is quite evident that cellular damage and DNA genotoxic effect are induced. Iron overload may play a critical role in exacerbating pre-existing morbidity or even unmask silent ones. Under these circumstances, iron chelation therapy could play an integral role in the management of these patients. This review entails an in depth analysis of iron overload in MDS patients; its pathophysiology, effect on survival, associated risks and diagnostic options. It also discusses management options in relation to chelation therapy used in MDS patients and the impact it has on survival, hematologic response and organ function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Calibration of shahid's analytical method for adulterated Zn-edta fertilizers by ion chromatography and atomic absorption spectroscopy

International Nuclear Information System (INIS)

Khan, M.S.A.; Akram, M.; Qazi, M.A.

2010-01-01

Chelated zinc fertilizers are usually recommended in calcareous alkaline soils to provide Zn nutrition in order to prevent possible Zn precipitation. In Punjab (Pakistan), Zn EDTA products are being manufactured, and marketed to meet the zinc requirement of various crops grown in Zn deficient soils. Under fertilizer control order, 1973 (amended), their quality has to be monitored by the Agriculture Department, Government of the Punjab. None of the traditional method was found suitable which can separate the mineral fraction from that of chelated adulterated fertilizer except for those methods based on ion chromatography. Calibration of ion chromatography method was carried out by determining the mineral Zn fraction leading to estimate remaining Zn EDTA fraction in fertilizer samples of adulterated nature i.e. mixture of chelated and mineral fraction. In order to achieve the objective atomic absorption spectroscopy was coupled with ion chromatography. The method offers a specific, reliable technique for determination of chelated zinc in fertilizers. In the first step chelation was broken down with concentrated sulphuric acid treatment and total zinc contents were determined by atomic absorption spectroscopy. In second step, non-chelated (mineral) portion of zinc was determined by ion chromatography using cation column and conductivity detector. Chelated zinc was calculated by subtracting non-chelated (mineral) fraction from total zinc contents. (author)

Trace element analysis of water using radioisotope induced X-ray fluorescence (Cd-109) and a preconcentration-internal standard method

International Nuclear Information System (INIS)

Alvarez, M.; Cano, W.

1986-10-01

Radioisotope induced X-ray fluorescence using Cd-109 was used for the determination of iron, nickel, copper, zinc, lead and mercury in water. These metals were concentrated by precipitation with the chelating agent APDC. The precipitated formed was filtered using a membrane filter. Cobalt was added as an internal standard. Minimum detection limit, sensitivities and calibration curves linearities have been obtained to find the limits of the method. The usefulness of the method is illustrated analysing synthetic standard solutions. As an application analytical results are given for water of a highly polluted river area. (Author)

Effects of Nano Chelated Zinc and Mycorrhizal Fungi Inoculation on Some Agronomic and Physiological Characteristics of Safflower (Carthamus tinctorius L. under Drought Stress Conditions

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E Rezaei Chiyaneh

2017-06-01

symbiosis, increased significantly soluble sugars and proline contents. Elicitation of results showed that inoculation of mycorrhizal under water stress conditions could be increase water and nutrients uptake by increasing uptake of root and could improve plant tolerance against to drought stress. On the other hand, given the role of zinc in plants in drought stress conditions, the existence enough amount of this nutrient is effective to adjust consistency. Conclusions The results of the study showed that the application of Nano chelated zinc fertilizer and mycorrhizal fungi had significant improvements on some physiological characteristics of safflower beside, yield and yield components also increased. Because of more zinc uptake and symbiosis with mycorrhizal fungi, water and minerals uptake increased thus decreased negative effects of drought stress. Due to global attention to sustainable agriculture, environment and human health, nanotechnology and biofertilizers can be as alternative fertilization methods. According to recent years conditions as decline in groundwater, reduce rainfall and water shortages, revising oilseeds nutritional management is necessary.

A Powerful Mitochondria-Targeted Iron Chelator Affords High Photoprotection against Solar Ultraviolet A Radiation.

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Reelfs, Olivier; Abbate, Vincenzo; Hider, Robert C; Pourzand, Charareh

2016-08-01

Mitochondria are the principal destination for labile iron, making these organelles particularly susceptible to oxidative damage on exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The labile iron-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via adenosine triphosphate depletion. Therefore, targeted removal of mitochondrial labile iron via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria-homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, adenosine triphosphate depletion, and the ensuing necrotic cell death in skin fibroblasts, and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of the UVA component of sunlight. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mercury removal in utility wet scrubber using a chelating agent

Science.gov (United States)

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.

Purification of camel liver catalase by zinc chelate affinity chromatography and pH gradient elution: An enzyme with interesting properties.

Science.gov (United States)

Chafik, Abdelbasset; Essamadi, Abdelkhalid; Çelik, Safinur Yildirim; Mavi, Ahmet

2017-12-01

Climate change and increasing temperatures are global concerns. Camel (Camelus dromedarius) lives most of its life under high environmental stress in the desert and represent ideal model for studying desert adaptation among mammals. Catalase plays a key role in protecting cells against oxidative stress. For the first time, catalase from camel liver was purified to homogeneity by zinc chelate affinity chromatography using pH gradient elution, a better separation was obtained. A purification fold of 201.81 with 1.17% yield and a high specific activity of 1132539.37U/mg were obtained. The native enzyme had a molecular weight of 268kDa and was composed of four subunits of equal size (65kDa). The enzyme showed optimal activity at a temperature of 45°C and pH 7.2. Thiol reagents, β-Mercaptoethanol and D,L-Dithiothreitol, inhibited the enzyme activity. The enzyme was inhibited by Al 3+ , Cd 2+ and Mg 2+ , whereas Ca 2+ , Co 2+ and Ni 2+ stimulated the catalase activity. Reduced glutathione has no effect on catalase activity. The K m and V max of the enzyme for hydrogen peroxide were 37.31mM and 6185157U/mg, respectively. Sodium azide inhibited the enzyme noncompetitively with K i value of 14.43μM, the IC 50 was found to be 16.71μM. The properties of camel catalase were different comparing to those of mammalian species. Relatively higher molecular weight, higher optimum temperature, protection of reduced glutathione from hydrogen peroxide oxidation and higher affinity for hydrogen peroxide and sodium azide, these could be explained by the fact that camel is able to live in the intense environmental stress in the desert. Copyright © 2017 Elsevier B.V. All rights reserved.

Zinc Vacancy-Induced Room-Temperature Ferromagnetism in Undoped ZnO Thin Films

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Hongtao Ren

2012-01-01

Full Text Available Undoped ZnO thin films are prepared by polymer-assisted deposition (PAD and treated by postannealing at different temperatures in oxygen or forming gases (95%  Ar+5% H2. All the samples exhibit ferromagnetism at room temperature (RT. SQUID and positron annihilation measurements show that post-annealing treatments greatly enhance the magnetizations in undoped ZnO samples, and there is a positive correlation between the magnetization and zinc vacancies in the ZnO thin films. XPS measurements indicate that annealing also induces oxygen vacancies that have no direct relationship with ferromagnetism. Further analysis of the results suggests that the ferromagnetism in undoped ZnO is induced by Zn vacancies.

Overview of current chelation practices

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Y. Aydinok

2011-12-01

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

Alterations in Somatostatin Cells and Biochemical Parameters Following Zinc Supplementation in Gastrointestinal Tissue of St reptozotocin-Induced Diabetic Rats

International Nuclear Information System (INIS)

Bolkent, Sema; Bolkent, Sehnaz; Yanardag, Refiye; Mutlu, Ozgur; Yildirim, Sukriye

2006-01-01

Chronic hyperglycemia in diabetes is a major causative factor of free radical generation which further leads to many secondary diabetic complications via the damage to cellular proteins, membrane lipids, and nucleic acids. Zinc is an essential trace element in all living systems and plays a structural role in many proteins and enzymes. Somatostatin is known to have inhibitory effects on various gastrointestinal functions. Therefore, we determined somatostatin protein production and secretion levels, and biochemical and light microscopical changes following zinc supplementation in the gastrointestinal tract of streptozotocin (STZ)-diabetic rats. The animals were divided into four groups: Group I: control (untreated) animals; Group II: control animals given zinc sulfate; Group III: diabetic animals; and Group IV: diabetic animals given zinc sulfate. Zinc sulfate was given to the animals by gavage at a daily dose of 100 mg/kg body weight for 60 days. Diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg/kg. For histological studies, stomach and duodenum tissues were fixed in Bouin solution and sections stained with Masson’s trichrome and Periodic-Acid-Schiff. Tissue homogenates were used for protein, lipid peroxidation (LPO), glutathione (GSH), and nonenzymatic glycosylation (NEG) analyses. Zinc supplementation to the STZ-diabetic rats revealed the protective effect of zinc on these parameters. Zinc supplementation may contribute to prevent at least some complications of diabetes mellitus

Chelation in root canal therapy reconsidered.

Science.gov (United States)

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.

Further studies on selective radioprotection by organic zinc salts and synergism of zinc aspartate with WR 2721

International Nuclear Information System (INIS)

Floersheim, G.L.; Bieri, A.

1990-01-01

Protection of the haematocrit and thrombocytes by small doses of the aminothiol radioprotector WR 2721 was markedly improved by the concomitant administration of small doses of zinc aspartate. Zinc aspartate was the only one of the tested zinc salts not inhibiting the regression induced by radiotherapy of human tumours grown as xenografts in immunosuppressed mice. This also applied to zinc aspartate with WR 2721. A dose of zinc aspartate which afforded synergistic haematological protection did not enhance the toxicity of WR 2721. The synergism of zinc aspartate with WR 2721 and the differential radioprotection of the combined protocol may make it possible in clinical cancer radiotherapy to obtain selective radioprotection at a lower toxicity giving an improved therapeutic ratio compared with WR 2721 alone. (author)

Synthesis of Poly(hydroxamic Acid-Poly(amidoxime Chelating Ligands for Removal of Metals from Industrial Wastewater

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M. R. Lutfor

2011-01-01

Full Text Available Synthesis of poly(hydroxamic acid-poly(amidoxime chelating ligands were carried out from poly(methyl acrylate-co-acrylonitrile grafted sago starch and hydroxylamine in alkaline medium. The binding property of metal ions was performed and maximum sorption capacity of the copper was 3.20 mmol/ g and the rate of exchange of some metals was faster, i.e. t½ ≈ 7 min (average. Two types of wastewater containing chromium, zinc, nickel, copper and iron, etc. were used and the heavy metal recovery was found to be highly efficient, about 99% of the metals could be removed from the metal plating wastewater.

Biological behaviour of some 67Ga and 64Cu chelates

International Nuclear Information System (INIS)

Leonovicova, T.; Angelis, B.; Cifka, J.; Cifkova, I.

1984-01-01

Chelates of 67 Ga and 64 Cu with iminodiacetic acid (IDA) and its two phenyl derivatives as well as with nitrilotriacetic acid (NTA) and benzylnitrilotriacetic acid (BNTA) were prepared. All the chelates were found to be negatively charged. A study of the biological distribution of these chelates in rats during time intervals of 3 to 180 min showed that the chelate of 67 Ga with IDA substituted at a phenyl by a hydrophobic substituent is excreted by the kidneys into the urine at a much higher rate than the IDA chelate of 67 Ga. The excretion of NTA and BNTA chelates of 67 Ga is the opposite. Blood clearance of 64 Cu chelates is more rapid than that of 67 Ga chelates. Chelates of 64 Cu accumulate in the liver and with the bile are slowly excreted into the intestines, urinary excretion is negligible. (author)

Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: role of zinc and metallothionein.

Science.gov (United States)

McAleer, Mary Frances; Tuan, Rocky S

2004-12-01

Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Published 2005 Wiley-Liss, Inc.

Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.

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Yang, Qiaohong; Gupta, Romi

2018-01-19

UV is one of the major causes of DNA damage induced apoptosis. However, cancer cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify factors that protect cancer cells from UV-induced apoptosis, we performed a genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show that UV irradiation transcriptionally upregulates ZNF598 expression. Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels was up regulated upon UV irradiation, which was necessary for UV irradiation induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene expression, which matches with decrease in percentage of annexin V positive cell. Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and also increased annexin V positive cells. Collectively, these results demonstrate that ZNF598 is a UV irradiation regulated gene and its loss results in resistance to UV-induced apoptosis.

Physiological Responses of Some Iranian Grape Cultivars to Iron Chelate Application in Calcareous Soil

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H. Doulati Baneh

2016-07-01

index and leaf area differs significantly among tested cultivars. The highest and the lowest chlorophyll index were observed in Rasha and Keshmeshi Qermez cultivars, respectively. Fe chelate consumption up to 7.5 mg/kg significantly increased chlorophyll, leaf area, shoots growth and fresh weight of shoot and root compared to the control. The highest leaf area was related to Rasha cultivar in 7.5 mg/kg treatment. In all tested cultivars by increasing Fe concentration to 15 mg/kg, leaf area was decreased. According to the laboratory results, there was a significant difference in the concentrations of some macro and micro nutrient of leaves among tested cultivars. The highest amount of K, Fe, Mn and Zn was recorded in leaves of Rasha cultivar. Qezel uzum has also the highest P, N, Ca, Mg and Cu in its leaves. Application of 7.5 Fe mg /Kg soil increased calcium, magnesium and copper concentrations in leaves of Rasha cultivar and nitrogen concentration in Qezel uzum cultivar. In Keshmeshi Qermez cultivar, the sensitive cultivar to iron chlorosis, iron chelate consumption up to 7.5 Fe mg /Kg soil increased nitrogen, zinc and copper concentrations. Increase in iron consumption up to 15 mg/Kg soil caused significant increase in copper concentration. Among the study cultivars, Rasha significantly absorbed the highest iron, zinc, manganese and potassium from the soil and did not show iron chlorosis, so it can be as a suitable rootstock with respect to iron chlorosis. Conclusion: In this study we have studied the influence Fe-chelate on some features of three Iranian grapevine cultivars (Vitis vinifera L grown in calcareous soils. Our findings confirm the variable response of native grapevines to bicarbonate-induced iron deficiency. The most susceptible cultivar, Keshmeshi Qermez, have been very impaired by the calcareous soil; it produced less shoot growth and dry matter since these factors of the tolerant cultivars was decreased very little. The different behavior of potted

Zinc-Dependent Protection of Tobacco and Rice Cells From Aluminum-Induced Superoxide-Mediated Cytotoxicity

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Lin, Cun; Hara, Ayaka; Comparini, Diego; Bouteau, François; Kawano, Tomonori

2015-01-01

Al3+ toxicity in growing plants is considered as one of the major factors limiting the production of crops on acidic soils worldwide. In the last 15 years, it has been proposed that Al3+ toxicity are mediated with distortion of the cellular signaling mechanisms such as calcium signaling pathways, and production of cytotoxic reactive oxygen species (ROS) causing oxidative damages. On the other hand, zinc is normally present in plants at high concentrations and its deficiency is one of the most widespread micronutrient deficiencies in plants. Earlier studies suggested that lack of zinc often results in ROS-mediated oxidative damage to plant cells. Previously, inhibitory action of Zn2+ against lanthanide-induced superoxide generation in tobacco cells have been reported, suggesting that Zn2+ interferes with the cation-induced ROS production via stimulation of NADPH oxidase. In the present study, the effect of Zn2+ on Al3+-induced superoxide generation in the cell suspension cultures of tobacco (Nicotiana tabacum L., cell-line, BY-2) and rice (Oryza sativa L., cv. Nipponbare), was examined. The Zn2+-dependent inhibition of the Al3+-induced oxidative burst was observed in both model cells selected from the monocots and dicots (rice and tobacco), suggesting that this phenomenon (Al3+/Zn2+ interaction) can be preserved in higher plants. Subsequently induced cell death in tobacco cells was analyzed by lethal cell staining with Evans blue. Obtained results indicated that presence of Zn2+ at physiological concentrations can protect the cells by preventing the Al3+-induced superoxide generation and cell death. Furthermore, the regulation of the Ca2+ signaling, i.e., change in the cytosolic Ca2+ ion concentration, and the cross-talks among the elements which participate in the pathway were further explored. PMID:26648960

Transient fluctuations of intracellular zinc ions in cell proliferation

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Li, Yuan [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Maret, Wolfgang, E-mail: womaret@utmb.edu [Division of Human Nutrition, Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

2009-08-15

Zinc is essential for cell proliferation, differentiation, and viability. When zinc becomes limited for cultured cells, DNA synthesis ceases and the cell cycle is arrested. The molecular mechanisms of actions of zinc are believed to involve changes in the availability of zinc(II) ions (Zn{sup 2+}). By employing a fluorescent Zn{sup 2+} probe, FluoZin-3 acetoxymethyl ester, intracellular Zn{sup 2+} concentrations were measured in undifferentiated and in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Intracellular Zn{sup 2+} concentrations are pico- to nanomolar in PC12 cells and are higher in the differentiated than in the undifferentiated cells. When following cellular Zn{sup 2+} concentrations for 48 h after the removal of serum, a condition that is known to cause cell cycle arrest, Zn{sup 2+} concentrations decrease after 30 min but, remarkably, increase after 1 h, and then decrease again to about one half of the initial concentration. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, decreases after both serum starvation and zinc chelation. Two peaks of Zn{sup 2+} concentrations occur within one cell cycle: one early in the G1 phase and the other in the late G1/S phase. Thus, fluctuations of intracellular Zn{sup 2+} concentrations and established modulation of phosphorylation signaling, via an inhibition of protein tyrosine phosphatases at commensurately low Zn{sup 2+} concentrations, suggest a role for Zn{sup 2+} in the control of the cell cycle. Interventions targeted at these picomolar Zn{sup 2+} fluctuations may be a way of controlling cell growth in hyperplasia, neoplasia, and diseases associated with aberrant differentiation.

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Gao, Xiaolong [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China); Wang, Gangmin [Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040 (China); Shi, Ting [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Shao, Zhihong [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China); Zhao, Peng; Shi, Donglu [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Ren, Jie [Institute of Nano and Biopolymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804 (China); Lin, Chao, E-mail: chaolin@tongji.edu.cn [The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092 (China); Wang, Peijun, E-mail: tjpjwang@sina.com [Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065 (China)

2016-08-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T{sub 1}-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2′-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T{sub 1}-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. - Highlights: • Novel cationic gadolinium-chelated poly(urethane amide)s (GdCPUAs) are prepared. • GdCPUAs can induce a high transfection efficacy in different cancer cells. • GdCPUAs reveal good cyto-compatibility against cancer cells. • GdCPUAs may be applied as T{sub 1}-contrast agents for magnetic resonance imaging. • GdCPUAs hold high potential for cancer theranostics.

Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging

International Nuclear Information System (INIS)

Gao, Xiaolong; Wang, Gangmin; Shi, Ting; Shao, Zhihong; Zhao, Peng; Shi, Donglu; Ren, Jie; Lin, Chao; Wang, Peijun

2016-01-01

Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T 1 -weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2′-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T 1 -weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics. - Highlights: • Novel cationic gadolinium-chelated poly(urethane amide)s (GdCPUAs) are prepared. • GdCPUAs can induce a high transfection efficacy in different cancer cells. • GdCPUAs reveal good cyto-compatibility against cancer cells. • GdCPUAs may be applied as T 1 -contrast agents for magnetic resonance imaging. • GdCPUAs hold high potential for cancer theranostics.

Chelate-assisted phytoextraction of lead from contaminated soils

Energy Technology Data Exchange (ETDEWEB)

Cooper, E.M.; Sims, J.T.; Cunningham, S.D.; Huang, J.W.; Berti, W.R.

1999-12-01

Phytoextraction, a remediation strategy for lead (Pb)-contaminated soils that removes soil Pb through plant uptake and harvest, may be enhanced by use of synthetic chelates. The authors evaluated Pb desorption from four contaminated soils by seven chelates (CDTA, DTPA, EDDHA, EFTA, HEDTA, HEIDA, and NTA) at three rates. The three most effective chelates (CDTA, DTPA, and HEDTA) were used in greenhouse studies with an uncontaminated soil and a Pb-contaminated soil to determine the effect of chelate type and rate on growth, Pb uptake, and plant elemental composition. Lead desorption varied with chelate and soil and increased with chelate rate, averaging 948 mg Pb kg{sup {minus}1} at the 20 mmol kg{sup {minus}1} rate vs. 28 mg Pb kg{sup {minus}1} by the control. The general ranking of chelate effectiveness, based on total Pb desorbed, was HEDTA > CDTA > DTPA > EGTA > HEIDA > EDDHA {approximately} NTA. Plant uptake of Pb from the contaminated soil was enhanced by CDTA, DTPA, and HEDTA, but with even the most effective treatment (corn, high CDTA rate), the amount of Pb extracted by plants was rather low. Lead extractable by the Toxicity Characteristic Leaching Procedure (TCLP) was increased from 9 mg L{sup {minus}1} in the control to from 47 to 174 mg L{sup {minus}1} in soils treated with 20 mmol kg{sup {minus}1} CDTA or DTPA and chelates generally caused a shift in Pb from resistant to more soluble chemical fractions.

Exciplex electroluminescence and photoluminescence spectra of the new organic materials based on zinc complexes of sulphanylamino-substituted ligands.

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Kaplunov, Mikhail G; Krasnikova, Svetlana S; Nikitenko, Sergey L; Sermakasheva, Natalia L; Yakushchenko, Igor K

2012-04-03

We have investigated the electroluminescence spectra of the electroluminescent devices based on the new zinc complexes of amino-substituted benzothiazoles and quinolines containing the C-N-M-N chains in their chelate cycles. The spectra exhibit strong exciplex bands in the green to yellow region 540 to 590 nm due to interaction of the excited states of zinc complexes and triaryl molecules of the hole-transporting layer. For some devices, the intrinsic luminescence band of 460 nm in the blue region is also observed along with the exciplex band giving rise to an almost white color of the device emission. The exciplex band can be eliminated if the material of the hole-transporting layer is not a triarylamine derivative. We have also found the exciplex emission in the photoluminescence spectra of the films containing blends of zinc complex and triphenylamine material.

Chelating effect of silver nitrate by chitosan on its toxicity and growth performance in broiler chickens

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Yemdjie Mane Divine Doriane

2017-06-01

Full Text Available Objective: This study was conducted to investigate the chelating effect of silver nitrate (AgNO3 by chitosan on growth performances, hematological and biochemical parameters, and the histopathological structure of the liver and the kidney in broiler chicken. Materials and methods: A total of 192 day-old Cobb 500 strain chicks were randomly assigned to 3 treatments of 64 chicks each. Control group was fed on basal diet without supplement (R0 and the two others groups were fed on rations supplemented with 10 mg of unchelated (RAg or chelated (RCs-Ag AgNO3 per Kg of feed, respectively. Parameters that have been studied consisted of feed intake, weight gain, blood and serum biochemical, and histopathological analyses of liver and kidney. Results: Results revealed that chelation of AgNO3 by chitosan did not have any effect on growth performances and hematological parameters in chicken. However, chelated and unchelated AgNO3 increased the serum content in triglyceride, and cholesterol and decreased the serum content in creatinin, albumin and alanine aminotransferase (ALAT. Chelating AgNO3 with chitosan prevented and corrected the toxicity induced on the histological structure of liver and kidney. Conclusion: Chitosan can be used as a chelating agent to alleviate the harmful effects of AgNO3 as silver ion for poultry. [J Adv Vet Anim Res 2017; 4(2.000: 187-193

The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

International Nuclear Information System (INIS)

Al-Damegh, Mona Abdalla

2007-01-01

Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

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

Science.gov (United States)

Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

2014-01-01

Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog. © 2013.

Involvement of the Pleiotropic Drug Resistance Response, Protein Kinase C Signaling, and Altered Zinc Homeostasis in Resistance of Saccharomyces cerevisiae to Diclofenac ▿

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van Leeuwen, Jolanda S.; Vermeulen, Nico P. E.; Vos, J. Chris

2011-01-01

Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as a model eukaryote with which to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during the initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under the control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. We tested if these processes or pathways were directly involved in diclofenac toxicity or resistance. Of the pleiotropic drug resistance gene products, the multidrug transporter Pdr5p was crucially important for diclofenac tolerance. Furthermore, deletion of components of the cell wall stress-responsive PKC pathway increased diclofenac toxicity, whereas incubation of cells with the cell wall stressor calcofluor white before the addition of diclofenac decreased its toxicity. Also, diclofenac induced flocculation, which might trigger the cell wall alterations. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as were zinc-responsive genes. Paradoxically, deletion of the zinc-responsive transcription factor Zap1p or addition of the zinc chelator 1,10-phenanthroline significantly increased diclofenac toxicity, establishing a regulatory role for zinc in diclofenac resistance. In conclusion, we have identified three new pathways involved in diclofenac tolerance in yeast, namely, Pdr5p as the main contributor to the PDR response, cell wall signaling via the PKC pathway, and zinc homeostasis, regulated by Zap1p. PMID:21724882

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

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Kocdor H

2015-07-01

Full Text Available Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549 and p53-null (H1299 cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50 values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299

[Susceptibility of enterococci to natural and synthetic iron chelators].

Science.gov (United States)

Lisiecki, Paweł; Mikucki, Jerzy

2002-01-01

A total of 79 strains of enterococci belonging to 10 species were tested for susceptibility to natural and synthetic iron chelators. All strains produced siderophores. These enterococci were susceptible to three synthetic iron chelators only: 8-hydroxyquinoline, disodium versenate (EDTA) and o-phenanthroline. They were resistant to all other synthetic chelators: ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA), nitrilotriacetate, 2,2'-bipiridyl, salicylic acid, 8-hydroxy-5-sulphonic acid and to all natural chelators: ovotransferrine, human apotransferrine, horse apoferritine, desferrioxamine B, ferrichrome and rhodotorulic acid. The relations between susceptibility/resistance, iron assimilation and structure and stability constants of iron chelators were discussed.

Mixed ligand chelates of rare earths in aqueous solution

International Nuclear Information System (INIS)

Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

1981-01-01

Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

Decontaminating effectiveness of Ca-, Zn-, MnDTPA chelates in contamination with inner radioisotopes 137Cs, 144Ce, 131I, 90Sr

International Nuclear Information System (INIS)

Kossakowski, S.

1987-01-01

The studies were carried out on 240 rabbits divided into 4 groups, in which, after contamination with radioisotopes 137 Cs (A), 144 Ce (B), 131 I (C), 90 Sr (D), Ca-, Zn-, MnDTPA chelates were used in 12.5% water solutions in doses of 0.4 g/kg of body weight. The evaluation of the decontaminating effectiveness of the above DTPA compounds, taking into account veterinary-clinical and veterinary-sanitary aspects, was made after 1,2,4,6,15 days from the contamination. The results expressing the per cent values of radioactivity of the organs are presented in individual groups. From these data it can be assumed for practical veterinary purposes that Ca-, Zn-, MnDTPA chelates show an effective action with respect to the veterinary-clinical aspect in contamination with radiocerium and with respect to the veterinary-sanitary aspect in contamination with radiocerium and radioiodine; less effective action with respect to the veterinary-sanitary aspect and ineffective with respect to the veterinary-clinical aspect in contamination with radiocesium; negative one with respect to both aspects in contamination with radiostrontium. As regards the individual chelating compounds, the most effective can be recognized sodium zinc salt of DTPA. 58 refs., 4 tabs. (author)

Effect of zinc gluconate, sage oil on inflammatory patterns and hyperglycemia in zinc deficient diabetic rats.

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Elseweidy, Mohamed M; Ali, Abdel-Moniem A; Elabidine, Nabila Zein; Mursey, Nada M

2017-11-01

The relationship between zinc homeostasis and pancreatic function had been established. In this study we aimed firstly to configure the inflammatory pattern and hyperglycemia in zinc deficient diabetic rats. Secondly to illustrate the effect of two selected agents namely Zinc gluconate and sage oil (Salvia Officinalis, family Lamiaceae). Rats were fed on Zinc deficient diet, deionized water for 28days along with Zinc level check up at intervals to achieve zinc deficient state then rats were rendered diabetic through receiving one dose of alloxan monohydrate (120mg/kg) body weight, classified later into 5 subgroups. Treatment with sage oil (0.042mg/kg IP) and Zinc gluconate orally (150mg/kg) body weight daily for 8 weeks significantly reduced serum glucose, C-reactive protein (CRP), Tumor necrosis factor alpha (TNF- α), interleukins-6 1 β, inflammatory8 (IFN ȣ), pancreatic 1L1-β along with an increase in serum Zinc and pancreatic Zinc transporter 8 (ZNT8). Histopathological results of pancreatic tissues showed a good correlation with the biochemical findings. Both sage oil and zinc gluconate induced an improvement in the glycemic and inflammatory states. This may be of value like the therapeutic agent for diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of zinc treatment on intestinal motility in experimentally ...

African Journals Online (AJOL)

Effect of zinc treatment on intestinal motility in experimentally induced diarrhea in rats. ... Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions / salts (ORS) can reduce the ...

Chelating agents in pharmacology, toxicology and therapeutics

International Nuclear Information System (INIS)

1988-01-01

The proceedings contain 71 abstracts of papers. Fourteen abstracts were inputted in INIS. The topics covered include: the effects of chelating agents on the retention of 63 Ni, 109 Cd, 203 Hg, 144 Ce, 95 Nb and the excretion of 210 Po, 63 Ni, 48 V, 239 Pu, 241 Am, 54 Mn; the applications of tracer techniques for studies of the efficacy of chelation therapy in patients with heart and brain disorders; and the treatment of metal poisoning with chelating agents. (J.P.)

Studies of zinc(II in pharmaceutical and biological samples by extractive spectrophotometry: using pyridoxal-4-phenyl-3-thiosemicarbazone as chelating reagent

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Sarma L. Subramanyam

2006-01-01

Full Text Available Pyridoxal-4-phenyl-3-thiosemicarbazone (PPT is proposed as a new sensitive reagent for the sensitive extractive spectrophotometric determination of zinc(II. PPT reacts with zinc(II in the pH range 5.0-6.0 to form a yellow colored complex, which was well extracted into n-butanol. The absorbance value of Zn(II-PPT complex was measured at different intervals of time at 430 nm, to ascertain the stability of the complex. It was observed that the color development was instantaneous and stable for more than 48 h. The system obeyed Beer's law up to 6.0 µg mL-1 of zinc(II, with an excellent linearity in terms of correlation coefficient value of 0.999. The molar absorptivity and Sandell's sensitivity of the extracted species is 1.6 X 10(4 L mol-1 cm-1 and 4.085 X 10-3 µg cm-2 at 430 nm. The detection limit of the method is 0.04 µg mL-1. To assess precision of the method, determinations were carried out at different concentrations; the relative standard deviation does not exceed 3.1%. The composition of the zinc(II complex with PPT was studied by the method of Job's continuous variation, molar ratio method, Asmus' method and slope ratio method. It has been satisfactorily applied for the determination of zinc(II, when present alone or in presence of diverse ions, which are usually associated with zinc(II in pharmaceutical and biological samples. Various certified reference materials (NIST 1573, NBS 1572 and NIST SRM 8435 have been tested for the determination of zinc for evaluating the accuracy of the developed method. The results of the proposed method are in agreement with flame atomic absorption spectometry.

Zinc, nitrogen and salinity interaction on agronomic traits and some ...

African Journals Online (AJOL)

use

2011-11-23

Nov 23, 2011 ... percentage decreased due to nitrogen, zinc and salinity in the first year but .... Analysis of variance on canola traits affected by nitrogen, zinc and salinity at ...... a result less of the latter are available for fat synthesis ... Na+ and Cl- in plant tissues, effects of nitrogen and zinc ... Zinc alleviates cadmium-induced.

Zinc in Infection and Inflammation.

Science.gov (United States)

Gammoh, Nour Zahi; Rink, Lothar

2017-06-17

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

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Crowell, Kristen T; Kelleher, Shannon L; Soybel, David I; Lang, Charles H

2016-11-01

Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Levels of semenogelin in human spermatozoa decrease during capacitation: involvement of reactive oxygen species and zinc.

Science.gov (United States)

de Lamirande, E; Lamothe, G

2010-07-01

Semenogelin (Sg), the main protein of human semen coagulum, prevents sperm capacitation. The objective of this study was to examine the role of Sg and its mechanism of action. Sg blocked sperm capacitation triggered by various stimuli, via inhibition of superoxide anion (O(2)*-; luminescence assay) and nitric oxide (NO*; tested using diaminofluorescein) generation. Triton-soluble and -insoluble sperm fractions contained Sg and Sg peptides (immunoblotting), the level of which decreased with initiation of capacitation. This drop was prevented by superoxide dismutase and NO* synthase inhibitor and was reproduced by addition of O(2)*- and NO*. Zinc (Zn(2+)) blocked and a zinc chelator (TPEN) promoted the decline in Sg levels. There was a decreased labelling of Sg on the head in capacitating spermatozoa with the two fixation techniques tested (immunocytochemistry). Reactive oxygen species (ROS) (O(2)*- and NO*) caused, these changes, and zinc prevented them. Spermatozoa quickly internalized Sg upon incubation and Sg was then rapidly degraded in a zinc-inhibitable manner. Sg blocked capacitation mainly via inhibition of ROS generation. Spermatozoa appeared permeable to Sg and processed Sg in a zinc-inhibitable fashion. ROS themselves could promote sperm disposal of Sg which maybe one of the mechanisms that allows initiation of capacitation.

Role of chelates in magnetic resonance imaging studies

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Tripathi Laxmi

2009-01-01

Full Text Available Imaging studies are tests performed with a variety of techniques that produce pictures of the inside of a patient′s body. Magnetic resonance imaging (MRI is an imaging technique based on the principles of nuclear magnetic resonance. MRI uses a powerful magnetic field, radio waves, and a computer to produce detailed pictures of organs, soft tissues, bone, and virtually all other internal body structures. Chelates have a wide application in such imaging techniques. Chelates in imaging studies are used alone as radioactive agents or conjugated to monoclonal antibodies or to DNA as radioactive agents. Technetium chelates and gadolinium chelates are being widely used as magnetic resonance contrast media.

Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae.

Science.gov (United States)

Dziedzic, Slawomir A; Caplan, Allan B

2011-05-01

Eukaryotes use a common set of genes to perform two mechanistically similar autophagic processes. Bulk autophagy harvests proteins nonselectively and reuses their constitutents when nutrients are scarce. In contrast, different forms of selective autophagy target protein aggregates or damaged organelles that threaten to interfere with growth. Yeast uses one form of selective autophagy, called cytoplasm-to-vacuole targeting (Cvt), to engulf two vacuolar enzymes in Cvt vesicles ("CVT-somes") within which they are transported to vacuoles for maturation. While both are dispensable normally, bulk and selective autophagy help sustain life under stressful conditions. Consistent with this view, knocking out several genes participating in Cvt and specialized autophagic pathways heightened the sensitivity of Saccharomyces cerevisiae to inhibitory levels of Zn(2+). The loss of other autophagic genes, and genes responsible for apoptotic cell death, had no such effect. Unexpectedly, the loss of members of a third set of autophagy genes heightened cellular resistance to zinc as if they encoded proteins that actively contributed to zinc-induced cell death. Further studies showed that both sensitive and resistant strains accumulated similar amounts of H2O2 during zinc treatments, but that more sensitive strains showed signs of necrosis sooner. Although zinc lethality depended on autophagic proteins, studies with several reporter genes failed to reveal increased autophagic activity. In fact, microscopy analysis indicated that Zn(2+) partially inhibited fusion of Cvt vesicles with vacuoles. Further studies into how the loss of autophagic processes suppressed necrosis in yeast might reveal whether a similar process could occur in plants and animals.

Obligatory reduction of ferric chelates in iron uptake by soybeans.

Science.gov (United States)

Chaney, R L; Brown, J C; Tiffin, L O

1972-08-01

The contrasting Fe(2+) and Fe(3+) 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 Fe(3+)-chelates. EDDHA binds Fe(3+) strongly, but Fe(2+) weakly; BPDS binds Fe(2+) strongly but Fe(3+) weakly. Addition of an excess of BPDS to nutrient solutions containing Fe(3+)-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 Fe(3+)-chelates appear to require reduction of Fe(3+)-chelate to Fe(2+)-chelate at the root, with Fe(2+) being the principal form of Fe absorbed by soybean.

Lisina digestível e zinco orgânico para frangos de corte machos na fase de 22 a 42 dias de idade Digestible lysine and zinc chelate for male broilers from 22 to 42 days of age

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Messias Alves da Trindade Neto

2010-11-01

Full Text Available Os efeitos dietéticos de lisina digestível e zinco quelato para frangos de corte machos entre 22 e 42 dias de idade foram avaliados em dois ensaios experimentais. Adotou-se o delineamento inteiramente casualizado em arranjo fatorial 5 × 2, com cinco níveis de lisina (0,841; 0,876; 0,997; 1,022 e 1,030% e dois de zinco (43 e 243 ppm. No primeiro ensaio, utilizaram-se 900 aves com peso médio inicial de 957,4 g distribuídas em parcelas experimentais de 30 aves e três repetições e, no segundo ensaio, 180 frangos com peso médio inicial de 866,22 g, divididos em parcelas de três aves e seis repetições. As características avaliadas foram desempenho, rendimento de cortes e composição corporal (1º ensaio, balanço de nitrogênio e digestibilidade aparente das dietas (2º ensaio. Houve interação entre os níveis de lisina e zinco para o ganho de peso, a conversão alimentar, a matéria seca ingerida e o balanço energético. Os rendimentos de peito, coxa e sobrecoxa tiveram aumentos lineares em resposta ao acréscimo no nível de lisina digestível na dieta. O melhor desempenho foi obtido com o nível de 0,997% de lisina digestível (ou 1,134% lisina total e de 43 ppm de zinco. Para maior rendimento dos cortes, o nível de lisina digestível recomendável deve ser no mínimo 1,002% (ou 1,139% de lisina total, independentemente dos níveis de zinco quelato. A maior inclusão de zinco em dietas para frangos de corte dos 22 aos 42 dias de idade não melhora a utilização da lisina na dieta e aumenta a deposição de gordura corporal.The dietary effects of digestible lysine and chelate zinc for male broiler chickens from 22 to 42 days of age were evaluated in two experimental assays. A complete randomized block experimental design in a 5 × 2 factorial, with five lysine levels (0.841, 0.876, 0.997, 1.022 and 1.030% and two levels of zinc (43 and 243 ppm was used. In the first assay, it was used 900 birds with initial average weight 957.4 g

Evaluation of genotoxicity induced by hydrogen peroxide in the presence of ions chelator Fe2+ (2,2'-dipyridyl) and of Cu2+(neocuproine), in Escherichia coli: involvement of DNA repair mechanisms in the bacteria survival

International Nuclear Information System (INIS)

Almeida, Carlos Eduardo Bonacossa de

1998-01-01

Prior incubation of the E. coli cultures with the iron ions chelator 2,2'-dipyridyl (1 mM) caused an intensification of the lethality and the mutagenesis induced by the hydrogen peroxide, mainly at high concentrations (20 mM). It was also detected an enhancement of DNA strand breaks in this condition. The addition of the copper ions chelator neocuproine blocked partially this phenomenon. The enzymes XthA and Nfo act alternatively in the repair of the lesions induced by H 2 O 2 in the presence of 2,2'-dipyridyl. H 2 O 2 can act synergistically with neocuproine in killing E. coli, causing an enhancement in DNA strand breaks. The recombinational repair, the UvrABC excinuclease and Fpg function appeared to participate in the repair of the synergistic lesions. (author)

Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains

International Nuclear Information System (INIS)

Vallee, B.L.; Auld, D.S.; Coleman, J.E.

1991-01-01

The authors recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a zinc cluster akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is ∼3.5 angstrom. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is ∼13 angstrom, and in this instance, a zinc twist is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native zinc fingers, structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

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de Queiroz, Camila A A; Fonseca, Said Gonçalves C; Frota, Priscila B; Figueiredo, Italo L; Aragão, Karoline S; Magalhães, Carlos Emanuel C; de Carvalho, Cibele B M; Lima, Aldo Ângelo M; Ribeiro, Ronaldo A; Guerrant, Richard L; Moore, Sean R; Oriá, Reinaldo B

2014-08-05

WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

Zinc in Infection and Inflammation

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Nour Zahi Gammoh

2017-06-01

Full Text Available Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

Application of sequential extraction analysis to electrokinetic remediation of cadmium, nickel and zinc from contaminated soils

International Nuclear Information System (INIS)

Giannis, Apostolos; Pentari, Despina; Wang, Jing-Yuan; Gidarakos, Evangelos

2010-01-01

An enhanced electrokinetic process for the removal of cadmium (Cd), nickel (Ni) and zinc (Zn) from contaminated soils was performed. The efficiency of the chelate agents nitrilotriacetic acid (NTA), diethylenetriaminepentaacetic acid (DTPA) and diaminocycloexanetetraacetic acid (DCyTA) was examined under constant potential gradient (1.23 V/cm). The results showed that chelates were effective in desorbing metals at a high pH, with metal-chelate anion complexes migrating towards the anode. At low pH, metals existing as dissolved cations migrated towards the cathode. In such conflicting directions, the metals accumulated in the middle of the cell. Speciation of the metals during the electrokinetic experiments was performed to provide an understanding of the distribution of the Cd, Ni and Zn. The results of sequential extraction analysis revealed that the forms of the metals could be altered from one fraction to another due to the variation of physico-chemical conditions throughout the cell, such as pH, redox potential and the chemistry of the electrolyte solution during the electrokinetic treatment. It was found that binding forms of metals were changed from the difficult type to easier extraction type.

Application of sequential extraction analysis to electrokinetic remediation of cadmium, nickel and zinc from contaminated soils

Energy Technology Data Exchange (ETDEWEB)

Giannis, Apostolos, E-mail: apostolos.giannis@enveng.tuc.gr [Department of Environmental Engineering, Technical University of Crete, Politechnioupolis, Chania 73100 (Greece); Pentari, Despina [Department of Mineral Resources Engineering, Technical University of Crete, Politechnioupolis, Chania 73100 (Greece); Wang, Jing-Yuan [Residues and Resource Reclamation Centre (R3C), Nanyang Technological University, 50 Nanyang Avenue, 639798 Singapore (Singapore); Gidarakos, Evangelos, E-mail: gidarako@mred.tuc.gr [Department of Environmental Engineering, Technical University of Crete, Politechnioupolis, Chania 73100 (Greece)

2010-12-15

An enhanced electrokinetic process for the removal of cadmium (Cd), nickel (Ni) and zinc (Zn) from contaminated soils was performed. The efficiency of the chelate agents nitrilotriacetic acid (NTA), diethylenetriaminepentaacetic acid (DTPA) and diaminocycloexanetetraacetic acid (DCyTA) was examined under constant potential gradient (1.23 V/cm). The results showed that chelates were effective in desorbing metals at a high pH, with metal-chelate anion complexes migrating towards the anode. At low pH, metals existing as dissolved cations migrated towards the cathode. In such conflicting directions, the metals accumulated in the middle of the cell. Speciation of the metals during the electrokinetic experiments was performed to provide an understanding of the distribution of the Cd, Ni and Zn. The results of sequential extraction analysis revealed that the forms of the metals could be altered from one fraction to another due to the variation of physico-chemical conditions throughout the cell, such as pH, redox potential and the chemistry of the electrolyte solution during the electrokinetic treatment. It was found that binding forms of metals were changed from the difficult type to easier extraction type.

Metal chelates of phosphonate-containing ligands-III Analytical applications of N,N,N',N'-ethylenediaminetetra(methylenephosphonic) acid.

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Zaki, M T; Rizkalla, E N

1980-05-01

N,N*,N',N'-Ethylenediaminetetra(methylenephosphonic) acid is used as a titrant for the direct determination of Cu, Co and Ni, with murexide as indicator. Indirect titrimetric procedures are suggested for the determination of silver, mercury, zinc and cyanide and both direct and indirect methods are applied for the analysis of binary mixtures of silver (or mercury) and copper (cobalt or nickel). The stoichiometry of the reaction, interferences of some metal ions and the pH effects on the complexation reactions are discussed. The values of the equilibrium constants of the protonated CuH(n)L (n = 1, 2, 3 and 4) as well as the unprotonated CuL chelates have been measured.

Metal regeneration of iron chelates in nitric oxide scrubbing

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

1997-08-19

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

Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation

International Nuclear Information System (INIS)

Dambara, Atsushi; Morinaga, Takatoshi; Fukuda, Naoyuki; Yamakawa, Yoshinori; Kato, Takuya; Enomoto, Atsushi; Asai, Naoya; Murakumo, Yoshiki; Matsuo, Seiichi; Takahashi, Masahide

2007-01-01

GZF1 is a zinc finger protein induced by glial cell-line-derived neurotrophic factor (GDNF). It is a sequence-specific transcriptional repressor with a BTB/POZ (Broad complex, Tramtrack, Bric a brac/Poxvirus and zinc finger) domain and ten zinc finger motifs. In the present study, we used immunoprecipitation and mass spectrometry to identify nucleolin as a GZF1-binding protein. Deletion analysis revealed that zinc finger motifs 1-4 of GZF1 mediate its association with nucleolin. When zinc fingers 1-4 were deleted from GZF1 or nucleolin expression was knocked down by short interference RNA (siRNA), nuclear localization of GZF1 was impaired. These results suggest that nucleolin is involved in the proper subcellular distribution of GZF1. In addition, overexpression of nucleolin moderately inhibited the transcriptional repressive activity of GZF1 whereas knockdown of nucleolin expression by siRNA enhanced its activity. Thus, the repressive activity of GZF1 is modulated by the level at which nucleolin is expressed. Finally, we found that knockdown of GZF1 and nucleolin expression markedly impaired cell proliferation. These findings suggest that the physiological functions of GZF1 may be regulated by the protein's association with nucleolin

Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

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Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

2012-03-01

Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

Expression analysis and biochemical characterization of beans plants biofortificated with zinc

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Sandra Pérez Álvarez

2017-09-01

Full Text Available The present work was carried out in greenhouse conditions at the Centro de Investigación en Alimentación y Desarrollo AC in Delicias, Chihuahua, México. Four different concentrations (0, 25, 50 and 100 μM L−1 of Zn chelate and sulfate were used to study the antioxidant system of Phaseolus vulgaris L. Three genes related with antioxidant activity [superoxide dismutase (SOD, glutathione peroxidase (GSH-Px and catalase (CAT] were selected for expression study. Results showed that when Zn chelate at 50 and 100 μM L−1 were applied SOD was repressed and GSH-Px expression was low at 0, 25 and 100 μM L−1 while with sulfate form SOD expression was low and GSH-Px expression was strong in all treatment. CAT was highly expressed in all form and treatments. For a biochemical study the same enzymes were spectrophotometrically measured. SOD activity shows differences in both forms of Zn, chelate form was different at 25, 50 and 100 μM L−1 with less activity at 100 μM L−1 and sulfate treatment shows differences in all concentrations used. GSH-Px activity shows significant differences with sulfate form at 25, 50 μM L−1 where at 50 μM the activity was higher and low at 100 μM L−1, CAT does not exhibit significant differences but with chelate treatment at 50–100 μM L−1 the activity was higher compared to sulfate. Finally, to raise the Zn concentration in bean under biofortification program is a promising strategy in cropping systems in order to increase the ingestion of zinc and antioxidant capacity in the general population and provided the benefits that this element offered in human health.

Effects of Sodium Citrate on the Ammonium Sulfate Recycled Leaching of Low-Grade Zinc Oxide Ores

Science.gov (United States)

Yang, Kun; Li, Shi-wei; Zhang, Li-bo; Peng, Jin-hui; Ma, Ai-yuan; Wang, Bao-bao

2016-03-01

The effects of sodium citrate on ammonium sulfate recycled leaching of low-grade zinc oxide ores were studied. By applying various kinds of detection and analysis techniques such as chemical composition analysis, chemical phase method, scanning electron microscopy and energy dispersive spectrum (SEM/EDS), X-ray diffraction (XRD) and Fourier-transforming infrared spectrum (FT-IR), zinc raw ore, its leaching slag and the functional mechanism of sodium citrate were investigated. Based on a comprehensive analysis, it can be concluded that in contrast to hemimorphite (Zn4Si2O7(OH)2 · H2O), amorphous smithsonite (ZnCO3) and zinc silicate (Zn2SiO4) prove to be refractory phases under ammonium sulfate leaching, while sodium citrate has a better chelating action with the refractory phases, resulting in a higher zinc leaching rate. Under conditions of [NH3]/[NH3]T molar ratio being 0.5, [NH3]T being 7.5 mol/L, [Na3C6H5O7] being 0.2 mol/L, S/L ratio being 1:5, temperature being 303 K, holding time being 1 h in each of the two stages, and stirring rate being 300 rpm, the leaching rate of zinc reached 93.4%. In this article, sulfate ammonium recycled technology also reveals its unique advantage in processing low-grade zinc oxide ores accompanied by high silicon and high alkaline gangue.

Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

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L.H. Santos

2004-08-01

Full Text Available We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg in male Wistar rats (180-300 g, N = 6 and compared it to free diclofenac (5 or 10 mg/kg and to the combination of diclofenac (5 or 10 mg/kg and zinc acetate (1.68 or 3.5 mg/kg. The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18ºC for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.

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

Science.gov (United States)

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.

Pseudomonas aeruginosa Trent and zinc homeostasis.

Science.gov (United States)

Davies, Corey B; Harrison, Mark D; Huygens, Flavia

2017-09-01

Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14 from target cells in its apoptosis-inducing activity

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Satoru Yui

2002-01-01

Full Text Available Background: Calprotectin is a calcium-binding and zinc-binding protein complex that is abundant in the cytosol of neutrophils. This factor is composed of 8 and 14 kDa subunits, which have also been termed migration inhibitory factor-related proteins MRP8 and MRP14. We previously reported that rat calprotectin purified from inflammatory neutrophils induces apoptosis of various tumor cells or normal fibroblasts in a zinc-reversible manner.

BWR fuel experience with zinc injection

International Nuclear Information System (INIS)

Levin, H.A.; Garcia, S.E.

1995-01-01

In 1982 a correlation between low primary recirculation system dose rates in BWR's and the presence of ionic zinc in reactor water was identified. The source of the zinc was primarily from Admiralty brass condensers. Plants with brass condensers are called ''natural zinc'' plants. Brass condensers were also a source of copper that was implicated in crude induced localized corrosion (CILC) fuel failures. In 1986 the first BWR intentionally injected zinc for the benefits of dose rate control. Although zinc alone was never implicated in fuel degradation of failures, a comprehensive fuel surveillance program was initiated to monitor fuel performance. Currently there are 14 plants that are injecting zinc. Six of these plants are also on hydrogen water chemistry. This paper describes the effect on both Zircaloy corrosion and the cruding characteristics as a result of these changes in water chemistry. Fuel rod corrosion was found to be independent of the specific water chemistry of the plants. The corrosion behavior was the same with the additions of zinc alone or zinc plus hydrogen and well within the operating experience for fuel without either of these additions. No change was observed in the amounts of crude deposited on the fuel rods, both for the adherent and loosely held deposits. One of the effects of the zinc addition was the trend to form more of the zinc rich iron spinel in the fuel deposits rather than the hematite deposits that are predominantly formed with non additive water chemistry

Effects of intracellular chelatable iron and oxidative stress on transcription of classical cellular glutathione peroxidase gene in murine erythroleukemia cells

International Nuclear Information System (INIS)

Fuchs, O.

1997-01-01

The effect of intracellular chelatable iron levels and of oxidative stress on nuclear classical cellular glutathione peroxidase (GSHPx-1) RNA nascent chain elongation (run-on transcription) and on the stability of cytoplasmic GSHPx-1 mRNA was investigated in murine erythroleukemia (MEL) cells. The amount in the intracellular low molecular mass iron pool was changed by incubation of MEL cells transformed by Friend virus with iron donors or iron chelators. Transcription in vitro in isolated nuclei from treated cells showed that the treatment with chelators (desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone) decrease the rate of nuclear GSHPx-1 RNA nascent chain elongation in both un-induced and with 5 mmol hexamethylenebisacetamide to erythroid differentiation induced MEL cells. Iron donors (diferric transferrin,, Fe-PIH or their combination) and t-butyl hydroperoxide (t-BuOOH) had the opposite effect on GSHPx-1 gene transcription in run-on experiments. On the other hand, 50 μmol DFO or 2.5 μmol t-BuOOH did not change the stability of cytoplasmic GSHPx-1 mRNA in both un-induced and induced MEL cells treated with 5 μmol actinomycin D and with or without these agents for 9 h. These findings indicate that iron and oxidative stress play their role at the transcriptional level of GSHPx-1 gene expression. (author)

ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES SRC-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)

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ZINC-INDUCED EGF RECEPTOR SIGNALING REQUIRES Src-MEDIATED PHOSPHORYLATION OF THE EGF RECEPTOR ON TYROSINE 845 (Y845)Weidong Wu1, Lee M. Graves2, Gordon N. Gill3 and James M. Samet4 1Center for Environmental Medicine and Lung Biology; 2Department of Pharmacology, University o...

Use of chelating agents as immovable phase in extraction chromatography

International Nuclear Information System (INIS)

Sebesta, F.

1978-01-01

Extraction chromatography using chelating agents is reviewed. The theory of element extraction by chelating agents and factors influencing this process (pH, extracting agent concentration in organic phase, masking agent concentration in aqueous phase) are briefly considered. The effect of kinetic factors on the extraction chromatography process is discussed. Ways of preparing columns are emphasized. Examples of using chelating reagents in various extraction chromatography systems are given. β-Diketones, oximes, hydroxamic acids, dithizon, diethyl dithiocarbamic acid are chosen as chelating agents

Uptake of soil P, Al, Fe, Mn, Mg and Ca by Italian rye grass (Lolium multiflorum Lam. induced by synthetic chelating agent

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Helinä Hartikainen

1981-05-01

Full Text Available The effect of a synthetic chelating compound on the dry matter yield and the uptake of soil P, Al, Fe, Mn, Mg and Ca by Italian rye grass was studied in a pot experiment with three mineral soil samples irrigated with water or 0.001 M Na2-EDTA(dinatrium salt of ethylenediaminetetraacetic acid solution. The Na2-EDTA treatment seemed not to affect the quantity of the dry matter yields, but it affected markedly their chemical composition. Increased contents of P, Al and Fe were found in all the harvests. In two soil samples the P supply was improved by 35—45 %. The accumulation of Al, Fe and Mn induced by Na2-EDTA tended to be the more effective the greater the stability constant for the corresponding metal-EDTA chelate was. Thus, the iron uptake increased most intensively, i.e. by 217—458 %, and that of aluminium by 33—120 %. On the basis of the first two harvests the manganese absorption by the rye grass seemed to decrease probably due to the enormous accumulation of iron. The results also suggested that the addition of Na2-EDTA to the soil was not able essentially to affect the magnesium and calcium supply to the plants.

Cathodic electrogenerated chemiluminescence of aromatic Tb(III) chelates at polystyrene-graphite composite electrodes

International Nuclear Information System (INIS)

Salminen, Kalle; Grönroos, Päivi; Tuomi, Sami; Kulmala, Sakari

2017-01-01

Tb(III) chelates exhibit intense hot electron-induced electrogenerated chemiluminescence during cathodic polarization of metal/polystyrene-graphite (M/PG) electrodes in fully aqueous solutions. The M/PG working electrode provides a sensitive means for the determination of aromatic Tb(III) chelates at nanomolar concentration levels with a linear log-log calibration curve spanning more than five orders of magnitude. The charge transport and other properties of these novel electrodes were studied by electrochemiluminescence measurements and cyclic voltammetry. The present composite electrodes can by utilized both under pulse polarization and DC polarization unlike oxide-coated metal electrodes which do not tolerate cathodic DC polarization. The present cost-effective electrodes could be utilized e.g. in immunoassays where polystyrene is extensively used as a solid phase for various bioaffinity assays by using electrochemiluminescent Tb(III) chelates or e.g. Ru(bpy) 3 2+ as labels. - Highlights: • Generation of hydrated electrons at Polystyrene-graphite electrodes. • The insulating polystyrene layer on the outer electrode surface seems necessary. • Hydrated electrons are able to produce chemiluminescence. • Strongest signal and lowest std. dev. achieved at same graphite weight fraction.

Chelating impact assessment of biological ad chemical chelates on metal extraction from contaminated soils

International Nuclear Information System (INIS)

Manwar, S.; Iram, S.

2014-01-01

Soil contamination is the result of uncontrolled waste dumping and poor practices by humans. Of all the pollutants heavy metals are of particular concern due to their atmospheric deposition, leaching capacity and non-biodegradability. Heavy metal containing effluent is discharged into the agricultural fields and water bodies. This results in the accumulation of heavy metals in soil and the crops grown on that soil. Studies have revealed detrimental impacts on soil fertility and the poor health of animals and humans. Phytoextraction is widely researched for remediation of heavy metal contaminated soil. To enhance the effect of phytoextraction heavy metals have to be available to the plants in soluble form. In this study the potential of different chelating agents was assessed in solubilizing the heavy metals making easy for plants to uptake them. For this purpose efficient chemical and biological chelating agent had to be identified. Along with that an optimum dose and application time for chemical chelating agent was determined. Ethylenediamine tetraacetic acid (EDTA), Diethylene triamine pentaacetic acid (DTPA), Nitriloacetic acid (NTA) were applied to the soil, containing Pb, Cr, Cu and Cd, at different concentrations and application time. Aspergillus niger and Aspergillus flavus were incubated in soil for different time periods. In correspondence with findings of the study, Pb and Cr were best solubilized by 5mM EDTA. For Cd and Cu 5mM DTPA carried out efficient chelation. NTA showed relatively inadequate solubilisation, although for Cr it performed equal to EDTA. A. niger and A. flavus instead of solubilizing adsorbed the metals in their biomass. Adsorption was mainly carried out by A. niger. (author)

Zinc translocation accelerates infarction after mild transient focal ischemia.

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Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

2002-01-01

Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

Glyphosate, a chelating agent-relevant for ecological risk assessment?

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Mertens, Martha; Höss, Sebastian; Neumann, Günter; Afzal, Joshua; Reichenbecher, Wolfram

2018-02-01

Glyphosate-based herbicides (GBHs), consisting of glyphosate and formulants, are the most frequently applied herbicides worldwide. The declared active ingredient glyphosate does not only inhibit the EPSPS but is also a chelating agent that binds macro- and micronutrients, essential for many plant processes and pathogen resistance. GBH treatment may thus impede uptake and availability of macro- and micronutrients in plants. The present study investigated whether this characteristic of glyphosate could contribute to adverse effects of GBH application in the environment and to human health. According to the results, it has not been fully elucidated whether the chelating activity of glyphosate contributes to the toxic effects on plants and potentially on plant-microorganism interactions, e.g., nitrogen fixation of leguminous plants. It is also still open whether the chelating property of glyphosate is involved in the toxic effects on organisms other than plants, described in many papers. By changing the availability of essential as well as toxic metals that are bound to soil particles, the herbicide might also impact soil life, although the occurrence of natural chelators with considerably higher chelating potentials makes an additional impact of glyphosate for most metals less likely. Further research should elucidate the role of glyphosate (and GBH) as a chelator, in particular, as this is a non-specific property potentially affecting many organisms and processes. In the process of reevaluation of glyphosate its chelating activity has hardly been discussed.

Chelation therapy to prevent diabetes-associated cardiovascular events.

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Diaz, Denisse; Fonseca, Vivian; Aude, Yamil W; Lamas, Gervasio A

2018-05-24

For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD. This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis. In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients.

Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH analogs: iron chelation, anti-oxidant and cytotoxic properties.

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Eliška Potůčková

Full Text Available Salicylaldehyde isonicotinoyl hydrazone (SIH is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability. Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O, which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

Microcirculatory effects of zinc on fructose-fed hamsters.

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Castiglione, R C; Barros, C M M R; Boa, B C S; Bouskela, E

2016-04-01

Fructose is a major dietary component directly related to vascular dysfunction and diseases such as obesity, diabetes, and hypertension. Zinc is considered a non-pharmacological alternative for treating diabetes due to its antioxidant and hyperglycemia-lowering effects in diabetic animals. Therefore, the aim of this study was to evaluate the effects of dietary zinc supplementation on the microcirculatory parameters of fructose-fed hamsters. Male hamsters (Mesocricetus auratus) were fed drinking water substituted by 10% fructose solution for 60 days, whereas control animals were fed drinking water alone. Their microcirculatory function was evaluated using cheek pouch preparation, as well as their blood glucose and serum insulin levels. Their microcirculatory responses to acetylcholine (ACh, an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator) as well as the increase in macromolecular permeability induced by 30 min of ischemia/reperfusion (I/R) were noted. Endothelium-dependent vasodilation was significantly increased in control animals with high zinc supplementation compared to the groups without zinc supplementation. Zinc was able to protect against plasma leakage induced by I/R in all control and fructose-fed groups, although the microvascular permeability was higher in animals fed drinking water substituted by 10% fructose solution compared to those fed filtered drinking water alone. Our results indicate that dietary zinc supplementation can improve microvascular dysfunction by increasing endothelial-dependent dilatation and reducing the increase in macromolecular permeability induced by I/R in fructose-fed animals. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Preparation, Spectroscopic Investigation and Biological Activity of New Mixed Ligand Chelates

International Nuclear Information System (INIS)

Alassbaly, F.S.; Ajaily, M.M.E.

2014-01-01

Preparation and investigation of new Co(II), Ni(II), Zn(II) and Cr(III) chelates with mixed ligands including Schiff base (L1) formed from the condensation of 4-dimethylaminobenzaldehyde with 2-aminophenol and anthranilic acid (L2) were studied. The obtained Schiff base and mixed ligand chelates were subjected to several physiochemical techniques, in terms of CHN elemental analyses, molar conductivity, magnetic moment measurements, infrared, proton nuclear magnetic resonance, electronic and mass spectra. The analytical data showed the formation of the Schiff base compound and the ratio of metal to ligands of the chelates are 1:1:1(M:L1:L2). The infrared spectral data exhibited that the used ligands behaving as bidentate ligands towards the metal ions. The proton nuclear magnetic resonance spectral data showed the signals of the active groups in the ligands which entered in chelation with Zn(II) metal ion. The electronic spectral results showed the existence of pie (phenyl ring) and n = pie (C=N) of the ligands and suggested the geometrical structures of the chelates. Meanwhile, the mass spectral data revealed the fragmentations of the Schiff base, anthranilic acid and their Ni(II) mixed ligand chelate has been preformed the only chelate conducted for justification. All the prepared mixed chelates were non-electrolyte in nature. The antibacterial activity of the Schiff base, anthranilic acid, metal salts and mixed ligand chelates were studied and found to be that mixed ligand chelates have the most biological activity in comparison to the free ligands and salts. (author)

Phytoextraction of 55-year-old wastewater-irrigated soil in a Zn-Pb mine district: effect of plant species and chelators.

Science.gov (United States)

Tai, YiPing; Yang, YuFen; Li, ZhiAn; Yang, Yang; Wang, JiaXi; Zhuang, Ping; Zou, Bi

2017-07-16

Untreated water from mining sites spreads heavy metal contamination. The present study assessed the phytoextraction performance of heavy metal-accumulating plants and the effects of chemical chelators on cadmium (Cd), lead (Pb), zinc (Zn), and copper (Cu) removal from paddy fields that have been continuously irrigated with mining wastewater from mines for 55 years. Outdoor pot experiments showed that the total Pb, Zn, and Cd content was lower in the rhizosphere soil of Amaranthus hypochondriacus than in that of Sedum alfredii, Solanum nigrum, and Sorghum bicolor. The aboveground biomass (dry weight) and relative growth rate of A. hypochondriacus were significantly higher than that of the other three species (P phytoextraction effect.

Increases in extracellular zinc in the amygdala in acquisition and recall of fear experience and their roles in response to fear.

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Takeda, A; Tamano, H; Imano, S; Oku, N

2010-07-14

The amygdala is enriched with histochemically reactive zinc, which is dynamically coupled with neuronal activity and co-released with glutamate. The dynamics of the zinc in the amygdala was analyzed in rats, which were subjected to inescapable stress, to understand the role of the zinc in emotional behavior. In the communication box, two rats were subjected to foot shock stress and anxiety stress experiencing emotional responses of foot-shocked rat under amygdalar perfusion. Extracellular zinc was increased by foot shock stress, while decreased by anxiety stress, suggesting that the differential changes in extracellular zinc are associated with emotional behavior. In rats conditioned with foot shock, furthermore, extracellular zinc was increased again in the recall of fear (foot shock) in the same box without foot shock. When this recall was performed under perfusion with CaEDTA, a membrane-impermeable zinc chelator, to examine the role of the increase in extracellular zinc, the time of freezing behavior was more increased, suggesting that zinc released in the lateral amygdala during the recall of fear participates in freezing behavior. To examine the role of the increase in extracellular zinc during fear conditioning, fear conditioning was also performed under perfusion with CaEDTA. The time of freezing behavior was more increased in the contextual recall, suggesting that zinc released in the lateral nucleus during fear conditioning also participates in freezing behavior in the recall. In brain slice experiment, CaEDTA enhanced presynaptic activity (exocytosis) in the lateral nucleus after activation of the entorhinal cortex. The present paper demonstrates that zinc released in the lateral amygdala may participate in emotional behavior in response to fear. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Construction and application of a zinc-specific biosensor for assessing the immobilization and bioavailability of zinc in different soils

International Nuclear Information System (INIS)

Liu Pulin; Huang Qiaoyun; Chen Wenli

2012-01-01

The inducibility and specificity of different czcRS operons in Pseudomonas putida X4 were studied by lacZ gene fusions. The data of β-glycosidase activity confirmed that the czcR3 promoter responded quantitatively to zinc. A zinc-specific biosensor, P. putida X4 (pczcR3GFP), was constructed by fusing a promoterless enhanced green fluorescent protein (egfp) gene with the czcR3 promoter in the chromosome of P. putida X4. In water extracts of four different soils amended with zinc, the reporter strain detected about 90% of the zinc content of the samples. Both the bioavailability assessment and the sequential extraction analysis demonstrated that the immobilization of zinc was highly dependent on the physico-chemical properties of soils. The results also showed that the lability of zinc decreased over time. It is concluded that the biosensor constitutes an alternative system for the convenient evaluation of zinc toxicity in the environment. - Highlights: ► A zinc-specific bacterial biosensor was developed. ► Four spiked soils were used to test the application of this biosensor. ► The bioavailable zinc in soil-water extracts decreased due to aging. ► The immobilization and speciation of zinc were highly dependent on the soil type. - The immobilization and bioavailability of zinc in soil were investigated as a function of soil type and aging by a newly constructed zinc-specific biosensor coupled with chemical analysis.

The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.

Science.gov (United States)

Arsenault, Patrick R; Song, Daisheng; Chung, Yu Jin; Khurana, Tejvir S; Lee, Frank S

2016-09-15

Prolyl hydroxylase domain protein 2 (PHD2) (also known as EGLN1) is a key oxygen sensor in mammals that posttranslationally modifies hypoxia-inducible factor α (HIF-α) and targets it for degradation. In addition to its catalytic domain, PHD2 contains an evolutionarily conserved zinc finger domain, which we have previously proposed recruits PHD2 to the HSP90 pathway to promote HIF-α hydroxylation. Here, we provide evidence that this recruitment is critical both in vitro and in vivo We show that in vitro, the zinc finger can function as an autonomous recruitment domain to facilitate interaction with HIF-α. In vivo, ablation of zinc finger function by a C36S/C42S Egln1 knock-in mutation results in upregulation of the erythropoietin gene, erythrocytosis, and augmented hypoxic ventilatory response, all hallmarks of Egln1 loss of function and HIF stabilization. Hence, the zinc finger ordinarily performs a critical positive regulatory function. Intriguingly, the function of this zinc finger is impaired in high-altitude-adapted Tibetans, suggesting that their adaptation to high altitude may, in part, be due to a loss-of-function EGLN1 allele. Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Study of cyclization of chelating compounds using electrospray ionization mass spectrometry

International Nuclear Information System (INIS)

Shi Ying; Campbell, J.A.

2000-01-01

Electrospray ionization mass spectrometry (ESI-MS) was used for the study of cyclization of organic chelating compounds (chelators). Four chelating compounds were studied: Symmetrical ethylenediaminediacetic acid (s-EDDA), Unsymmetrical ethylenediaminediacetic acid (u-EDDA), N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and N-(2-hydroxyethyl)iminodiacetic acid (HEIDA). The chelators were cyclized with treatments of acids and heating. The open and cyclized form of the chelators were semi-quantified by both positive and negative ion modes ESI-MS. The kinetics of chelator cyclization was studied as a function of reaction temperature and the pH of the matrix. The cyclization of s-EDDA was found to be a pseudo-first order reaction in s-EDDA and overall second order. The cyclizations of HEIDA and HEDTA are reversible reactions. Higher temperature and lower pH favors cyclization. (author)

Effect of DHA and CoenzymeQ10 Against Aβ- and Zinc-Induced Mitochondrial Dysfunction in Human Neuronal Cells

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Nadia Sadli

2013-07-01

Full Text Available Background: Beta-amyloid (Aβ protein is a key factor in the pathogenesis of Alzheimer's disease (AD and it has been reported that mitochondria is involved in the biochemical pathway by which Aβ can lead to neuronal dysfunction. Coenzyme Q10 (CoQ10 is an essential cofactor involved in the mitochondrial electron transport chain and has been suggested as a potential therapeutic agent in AD. Zinc toxicity also affects cellular energy production by decreasing oxygen consumption rate (OCR and ATP turnover in human neuronal cells, which can be restored by the neuroprotective effect of docosahexaenoic acid (DHA. Method: In the present study, using Seahorse XF-24 Metabolic Flux Analysis we investigated the effect of DHA and CoQ10 alone and in combination against Aβ- and zinc-mediated changes in the mitochondrial function of M17 neuroblastoma cell line. Results: Here, we observed that DHA is specifically neuroprotective against zinc-triggered mitochondrial dysfunction, but does not directly affect Aβ neurotoxicity. CoQ10 has shown to be protective against both Aβ- and zinc-induced alterations in mitochondrial function. Conclusion: Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.

Desferrioxamine, an iron chelator, enhances HIF-1α accumulation via cyclooxygenase-2 signaling pathway

International Nuclear Information System (INIS)

Woo, Kyung Jin; Lee, Tae-Jin; Park, Jong-Wook; Kwon, Taeg Kyu

2006-01-01

Cyclooxygenase-2 (COX-2) is an important inducible enzyme in inflammation and is overexpressed in a variety of cancers. Evidence is rapidly accumulating that chronic inflammation may contribute to carcinogenesis through increase of cell proliferation, angiogenesis, and metastasis in a number of neoplasms, including colorectal carcinoma. In the present study, we investigated some mechanistic aspects of DFX-induced hypoxia-driven COX-2 expression. Desferrioxamine (DFX), an iron chelator, is known to upregulate inflammatory mediators. DFX induced the expression of COX-2 and accumulation of HIF-1α protein in dose-dependent manners, but hypoxia mimetic agent cobalt chloride (CoCl 2 ) induced accumulation of HIF-1α protein but not increase of COX-2 expression. DFX-induced increase of COX-2 expression and HIF-1α protein level was attenuated by addition of ferric citrate. This result suggested that the iron chelating function of DFX was important to induce the increase of COX-2 and HIF-1α protein. PD98059 significantly inhibited the induction of COX-2 protein and accumulation of HIF-1α, suggesting that DFX-induced increase of HIF-1α and COX-2 protein was mediated, at least in part, through the ERK signaling pathway. In addition, pretreatment with NS-398 to inhibit COX-2 activity also effectively suppressed DFX-induced HIF-1α accumulation in human colon cancer cells, providing the evidence that COX-2 plays as a regulator of HIF-1α accumulation in DFX-treated colon cancer cells. Together, our findings suggest that iron metabolism may regulate stabilization of HIF-1α protein by modulating cyclooxygenase-2 signaling pathway

Zinc and the modulation of redox homeostasis

Science.gov (United States)

Oteiza, Patricia I.

2012-01-01

Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

Metal chelate process to remove pollutants from fluids

Science.gov (United States)

Chang, S.G.T.

1994-12-06

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

Sequestration of chelated copper by structural Fe(II): Reductive decomplexation and transformation of Cu{sup II}-EDTA

Energy Technology Data Exchange (ETDEWEB)

He, Hongping [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Wu, Deli, E-mail: wudeli@tongji.edu.cn [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Zhao, Linghui [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Luo, Cong [School of Civil and Environmental Engineering, Georgia Institute of Technology, GA 30332 (United States); Dai, Chaomeng; Zhang, Yalei [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China)

2016-05-15

Highlights: • Structural Fe(II) was found to reveal high sequestration potential in various chelated copper. • Chelated copper was reduced to Cu(0) and Cu{sub 2}O by =Fe(II), whcih was oxidized to Fe{sub 2}O{sub 3}·H{sub 2}O. • Both electron transfer and surface =Fe(II) were found to be crucial during chelated copper reduction. • The indispensible role of reductive decomplexation was identified in chelated copper sequestration. - Abstract: Chelated coppers, such as Cu{sup II}-EDTA, are characteristically refractory and difficult to break down because of their high stability and solubility. Cu{sup II}–EDTA sequestration by structural Fe(II) (=Fe(II)) was investigated intensively in this study. Up to 101.21 mgCu(II)/gFe(II) was obtained by =Fe(II) in chelated copper sequestration under near neutral pH condition (pH 7.70). The mechanism of Cu{sup II}-EDTA sequestration by =Fe(II) was concluded as follows: 3Cu{sup II}–EDTA + 7=Fe(II) + 9H{sub 2}O → Cu(0) ↓ + Cu{sub 2}O ↓ (the major product) + 2Fe{sub 2}O{sub 3}·H{sub 2}O ↓ + 3Fe{sup II}–EDTA +14H{sup +} Novel results strongly indicate that Cu{sup II} reductive transformation induced by surface =Fe(II) was mainly responsible for chelated copper sequestration. Cu(0) generation was initially facilitated, and subsequent reduction of Cu(II) into Cu(I) was closely combined with the gradual increase of ORP (Oxidation-Reduction Potential). Cu-containing products were inherently stable, but Cu{sub 2}O would be reoxidized to Cu(II) with extra-aeration, resulting in the release of copper, which was beneficial to Cu reclamation. Concentration diminution of Cu{sup II}–EDTA within the electric double layer and competitive adsorption were responsible for the negative effects of Ca{sup 2+}, Mg{sup 2+}. By generating vivianite, PO{sub 4}{sup 3−} was found to decrease surface =Fe(II) content. This study is among the first ones to identify the indispensible role of reductive decomplexation in chelated copper

Bifunctional chelates of Rh-105 and Au-199 as potential radiotherapeutic agents

International Nuclear Information System (INIS)

Troutner, D.E.; Schlemper, E.O.

1990-01-01

Since last year we have: continued the synthesis of pentadentate bifunctional chelating agents based on diethylene triamine; studied the chelation Rh-105, Au-198 (as model for Au-199) and Tc-99m with these agents as well as chelation of Pd-109, Cu-67, In-111, and Co-57 with some of them; synthesized a new class of potential bifunctional chelating agents based on phenylene diamine; investigated the behavior of Au-198 as a model for Au-199; begun synthesis of bifunctional chelating agents based on terpyridly and similar ligands; and continued attempts to produce tetradentate bifunctional chelates based on diaminopropane. Each of these will be addressed in this report

Protective Role of L- Carnitine and Zinc against γ-Radiation induced Cardiac and testicular Disorders in Albino Rats

International Nuclear Information System (INIS)

Ramadan, F. L.; Abdel-Monem, D.D.; Ismail, N.H.

2013-01-01

L-Carnitine is a dipeptide amino acid necessary for fat metabolism, it provides energy by transporting long-chain fatty acids to mitochondria to act as a fuel and it is considered a powerful antioxidant. In addition, zinc is an essential mineral which helps to increase the secretion of male sex hormones and raises the sperm count, so its combination with L-carnitine is useful for the fertility process. The present study aims to evaluate the potency of L-carnitine and zinc as radio- protective and curative agent pre and after exposure to γ-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by γ-irradiation by comet assay. Animals received L-carnitine (LC) and zinc (Zn) orally at the dose 9.45 mg/100 gm body wt./day for successive 20 days and then exposed to whole body gamma radiation at the dose 4 Gy (1 Gy for 4 days, day after day) on the 7th day from treatment with antioxidant. Histological examinations of heart and testis tissues showed that administration of LC and Zn have attenuated radiation induced damage and improved tissues architecture. Moreover, the observed amelioration in the tissues was accompanied by a remarkable decrease of their lipid peroxide levels (malondialdehyde (MDA)), together with an increase in glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities. Hormonal determinations of serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) which carried out for fertility assessment showed that whole body γ-irradiation of rats induced significant decrease in serum testosterone while FSH and LH were significantly increased as compared with control group. On the other hand, irradiation caused significant elevation in the total number of abnormal head, and / or tail of sperms in comparison to the control rats. The comet assay showed that exposure to γ-radiation induced DNA damage of sperms (tail moment values).

Symptomatic zinc deficiency in experimental zinc deprivation.

OpenAIRE

Taylor, C M; Goode, H F; Aggett, P J; Bremner, I; Walker, B E; Kelleher, J

1992-01-01

An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkal...

Laccase Immobilization by Chelated Metal Ion Coordination Chemistry

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Qingqing Wang

2014-09-01

Full Text Available In this work, amidoxime polyacrylonitrile (AOPAN nanofibrous membrane was prepared by a reaction between PAN nanofibers and hydroxylamine hydrochloride. The AOPAN nanofibrous membranes were used for four metal ions (Fe3+, Cu2+, Ni2+, Cd2+ chelation under different conditions. Further, the competition of different metal ions coordinating with AOPAN nanofibrous membrane was also studied. The AOPAN chelated with individual metal ion (Fe3+, Cu2+, Ni2+, Cd2+ and also the four mixed metal ions were further used for laccase (Lac immobilization. Compared with free laccase, the immobilized laccase showed better resistance to pH and temperature changes as well as improved storage stability. Among the four individual metal ion chelated membranes, the stability of the immobilized enzymes generally followed the order as Fe–AOPAN–Lac > Cu–AOPAN–Lac > Ni–AOPAN–Lac > Cd–AOPAN–Lac. In addition, the immobilized enzyme on the carrier of AOPAN chelated with four mixed metal ions showed the best properties.

f-Element Ion Chelation in Highly Basic Media

International Nuclear Information System (INIS)

Paine, R.T.

2000-01-01

A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelators for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

Transgenic expression of phytase in wheat endosperm increases bioavailability of iron and zinc in grains.

Science.gov (United States)

Abid, Nabeela; Khatoon, Asia; Maqbool, Asma; Irfan, Muhammad; Bashir, Aftab; Asif, Irsa; Shahid, Muhammad; Saeed, Asma; Brinch-Pedersen, Henrik; Malik, Kauser A

2017-02-01

Phytate is a major constituent of wheat seeds and chelates metal ions, thus reducing their bioavailability and so the nutritional value of grains. Transgenic plants expressing heterologous phytase are expected to enhance degradation of phytic acid stored in seeds and are proposed to increase the in vitro bioavailability of mineral nutrients. Wheat transgenic plants expressing Aspergillus japonicus phytase gene (phyA) in wheat endosperm were developed till T 3 generation. The transgenic lines exhibited 18-99 % increase in phytase activity and 12-76 % reduction of phytic acid content in seeds. The minimum phytic acid content was observed in chapatti (Asian bread) as compared to flour and dough. The transcript profiling of phyA mRNA indicated twofold to ninefold higher expression as compared to non transgenic controls. There was no significant difference in grain nutrient composition of transgenic and non-transgenic seeds. In vitro bioavailability assay for iron and zinc in dough and chapatti of transgenic lines revealed a significant increase in iron and zinc contents. The development of nutritionally enhanced cereals is a step forward to combat nutrition deficiency for iron and zinc in malnourished human population, especially women and children.

Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

Science.gov (United States)

Cho, Minsu; Hu, Guanggan; Caza, Mélissa; Horianopoulos, Linda C; Kronstad, James W; Jung, Won Hee

2018-01-01

Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

Chelating agents as stationary phase in extraction chromatography, ch. 11

International Nuclear Information System (INIS)

Sebesta, F.

1975-01-01

Chelating agents have been used largely in extraction chromatography for separations related to activation analysis, for concentration of metals from dilute solutions, and for preparation of radiochemically pure or carrier-free radionuclides. This review deals with the theory of extraction by chelating agents, the experimental technique, and the chelating agents and systems used (β-diketones, oximes, hydroxamic acid, dithizone and diethyldithiocarbamic acid)

The impact of steeping, germination and hydrothermal processing of wheat (Triticum aestivum L.) grains on phytate hydrolysis and the distribution, speciation and bio-accessibility of iron and zinc elements.

Science.gov (United States)

Lemmens, Elien; De Brier, Niels; Spiers, Kathryn M; Ryan, Chris; Garrevoet, Jan; Falkenberg, Gerald; Goos, Peter; Smolders, Erik; Delcour, Jan A

2018-10-30

Chelation of iron and zinc in wheat as phytates lowers their bio-accessibility. Steeping and germination (15 °C, 120 h) lowered phytate content from 0.96% to only 0.81% of initial dry matter. A multifactorial experiment in which (steeped/germinated) wheat was subjected to different time (2-24 h), temperature (20-80 °C) and pH (2.0-8.0) conditions showed that hydrothermal processing of germinated (15 °C, 120 h) wheat at 50 °C and pH 3.8 for 24 h reduced phytate content by 95%. X-ray absorption near-edge structure imaging showed that it indeed abolished chelation of iron to phytate. It also proved that iron was oxidized during steeping, germination and hydrothermal processing. It was further shown that zinc and iron bio-accessibility were respectively 3 and 5% in wheat and 27 and 37% in hydrothermally processed wheat. Thus, hydrothermal processing of (germinated) wheat paves the way for increasing elemental bio-accessibility in whole grain-based products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Observation of Fermi Arc Surface States Induced by Organic Memristive/Memcapacitive Devices with a Double-Helical Polarized Single-Wall Nanotube Membrane for Direct Chelating with Matrix Matelloproteinase-2

Directory of Open Access Journals (Sweden)

E. T. CHEN

2017-07-01

Full Text Available Matrix Matelloproteinase-2 (MMP-2 plays a key role in many diseases. A new type of dual-functioning device was developed for fast, direct ultrasensitive detection of MMP-2. We report a memristive/memcapacitive device with vertex double-helical polarized biomimetic protein nanotubules forming double membranes with potential gradient mimicking mitochondria’s inner double membrane has developed. We also report Fermi arcs with nodes on the surface of the nanostructured membrane was observed at the first time by using a 3D real-time - energy-current dynamic mapping method based on data obtained from the Cyclic Voltammetry (CV method. The memristive/memcapacitive device comprises a cross- linked organic polymer having single-wall cross-bar polarized nanotube self-assembling membrane (SAM on a gold chip, under an applied potential, a pair of vertex double- helical circular current flow induced the Fermi arcs states occurrence and these Fermi arcs promoted a direct chelating with zinc ions of the MMP-2 to become possible without any antibody, tracer, or reagent used at room temperature was accomplished. We observed the pair of Dirac Cones became alignment and strengthened with each other in the presence of MMP-2 compared without MMP-2. The MMP-2 can be detected with ag/mL level sensitivity and the value of Detection of Limits (DOL reached orders of magnitude lower than published reports with simplified procedures by a Chronoamperometry (CA method and a Double Step Chronopotentiometry (DSCPO method using NIST SRM 965A standard human serum, respectively. The results show a feasible application for developing the commercial fast and real-time MMP monitoring devices for various diseases.

Synthesis of ZnO nanocoatings by decomposition of zinc acetate induced by electrons emitted by indium

Energy Technology Data Exchange (ETDEWEB)

Svoboda, Ladislav [Department of Chemistry, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Institute of Environmental Technologies, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Dvorský, Richard [Department of Physics, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Regional Materials Science and Technology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Nanotechnology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Praus, Petr, E-mail: petr.praus@vsb.cz [Department of Chemistry, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Institute of Environmental Technologies, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Matýsek, Dalibor [Institute of Geological Engineering, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic); Bednář, Jiří [Nanotechnology Centre, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Ostrava 708 33 (Czech Republic)

2016-12-01

Graphical abstract: - Highlights: • Hexagonal ZnO was synthetized by the decomposition of zinc acetate under UV light. • Source of photogenerated electron was an indium plate. • ZnO nanocoatings were deposited on surface of silica nanoparticles. • Mean thickness of the ZnO nanocoatings was estimated by DLS at 13 nm. - Abstract: In this work, a new method for the synthesis of ZnO nanocoatings is presented. It was tested for the nanocoating of silica nanoparticles forming core/shell SiO{sub 2}/ZnO nanoparticles by the decomposition of zinc acetate in silica aqueous nanodispersions induced by electrons generated by a plate indium photocathode, which was irradiated with a UV Hg lamp with maximum intensity at the wavelength of 245 nm. The ZnO nanocoatings were examined by X-ray diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (DRS), photoluminescence spectroscopy (PLS), dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that ZnO of hexagonal structure formed nanocoatings with the mean thickness of 13 nm. The photocatalytic activity of ZnO nanocoatings was verified by the photocatalytic decomposition of methylene blue (MB). Such nanocoating procedure based on the electron-induced decomposition of suitable metal salts could be a promising method for various applications in nanotechnology.h.

Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.

Directory of Open Access Journals (Sweden)

José A G Pertusa

Full Text Available β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ chelators were present in the assay buffer solution. Albumin and Zn2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn2+ chelators promotes the conversion of "slow" Zn2+-insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn2+ chelators. These observations support the notion that the Zn2+-binding properties of albumin improve the dissociation of Zn2+-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.

Zinc

Science.gov (United States)

... Consumer Datos en español Health Professional Other Resources Zinc Fact Sheet for Consumers Have a question? Ask ... find out more about zinc? Disclaimer What is zinc and what does it do? Zinc is a ...

Ameliorative effects of selenium and zinc

African Journals Online (AJOL)

Methidathion-induced hematological, biochemical and hepatohistological alterations in rat: Ameliorative effects of selenium and zinc. L Barkat, A Boumendjel, C Abdennour, MS Boulakoud, A El Feki, M Messarah ...

The adsorption of chelating reagents on oxide minerals

International Nuclear Information System (INIS)

Bryson, M.A.W.

1984-06-01

This work constitutes a fundamental study of the interaction between chelating reagents and oxide minerals. The adsorption mechanisms have been elucidated for most of the systems generated by the oxides of copper(II) or iron(III) and chelating reagents octyl hydroxamate, N-phenylbenzohydroxamate, salicylaldoxime, 5-nitro-salicylaldoxime or 8-hydroxyquinoline. In order to better understand the adsorption process associated with copper(II) oxide, the oxide was recrystallized to produce a coarser material with a more uniform surface. This allowed the oxide surface to be viewed under the scanning electron microscope. A detailed investigation of the effect of the system variables; pH, conditioning period, concentration, temperature, surface area and dispersing reagent on the rate of precipitation of the copper chelate species of general form, Cu(chel) 2 , was made. In addition the chemical nature of the adsorbed species and the structural form of the precipitates were determined with the aid of infra-red spectroscopy and the scanning electron microscope. On the basis of these results a model has been formulated for the adsorption processes. The precipitation process was examined in more detail by the study of the adsorption of chelate on copper metal. Contact angle measurements of air bubbles on copper metal conditioned with chelate were related to the adsorption results in an attempt to isolate the optimum conditions for flotation of oxide minerals

Soft solution synthesis and intense visible photoluminescence of lamellar zinc oxide hybrids

International Nuclear Information System (INIS)

Sağlam, Özge

2013-01-01

Graphical abstract: -- In this study, we demonstrate the synthesis of layered zinc oxide films intercalated with dodecyl sulphate ions by a simple soft solution process. The presence of potassium (K + ) and lithium (Li + ) ions in the precursor solution of layered zinc hydroxide resulted in lamellar hybrid zinc oxide films instead of layered zinc hydroxides. On the other hand, the addition of nickel phthalocyanine induces zinc hydroxide host layers which exhibit an intense blue emission. This is also promoted by K + and Li + ions

Labelling of bacteria with indium chelates

International Nuclear Information System (INIS)

Kleinert, P.; Pfister, W.; Endert, G.; Sproessig, M.

1985-01-01

The indium chelates were prepared by reaction of radioactive indiumchloride with 10 μg oxine, 15 μg tropolone and 3 mg acetylacetone, resp. The formed chelates have been incubated with 10 9 germs/ml for 5 minutes, with labelling outputs from 90 to 95%. Both gram-positive (Streptococcus, Staphylococcus) and gram-negative bacteria (Escherichia coli) can be labelled. The reproductive capacity of the bacteria was not impaired. The application of indium labelled bacteria allows to show the distribution of microorganisms within the living organism and to investigate problems of bacterial adherence. (author)

Obtention of zinc polymethacrylate via free radicals induced by gamma radiation

International Nuclear Information System (INIS)

Urena N, F.; Flores E, J.

2000-01-01

The objective of this work was to synthesise the monomer of zinc methacrylate and subsequently to carry out the polymerization reaction with the purpose to obtain the compound desired, the zinc polymethacrylate. For this it was used a gamma radiation source, 60 Co, as initiator of the polymerization reaction. (Author)

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

Science.gov (United States)

Kim, Min-Hyun; Aydemir, Tolunay B; Kim, Jinhee; Cousins, Robert J

2017-07-18

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14 -/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.

Review of actinide decorporation with chelating agents

Energy Technology Data Exchange (ETDEWEB)

Ansoborlo, E. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/CETAMA), 30 - Marcoule (France); Amekraz, B.; Moulin, Ch. [CEA Saclay, Dept. de Physico-Chimie (DEN/DPC/SECR), 91 - Gif sur Yvette (France); Moulin, V. [CEA Saclay, Dir. du Developpement et de l' Innovation Nucleares (DEN/DDIN/MR), 91 - Gif Sur Yvette (France); Taran, F. [CEA Saclay (DSV/DBJC/SMMCB), 91 - Gif-sur-Yvette (France); Bailly, Th.; Burgada, R. [Centre National de la Recherche Scientifique (CNRS/LCSB/UMR 7033), 93 - Bobigny (France); Henge-Napoli, M.H. [CEA Valrho, Site de Marcoule (INSTN), 30 (France); Jeanson, A.; Den Auwer, Ch.; Bonin, L.; Moisy, Ph. [CEA Valrho, Dir. de l' Energie Nucleaire (DEN/DRCP/SCPS), 30 - Marcoule (France)

2007-10-15

In case of accidental release of radionuclides in a nuclear facility or in the environment, internal contamination (inhalation, ingestion or wound) with actinides represents a severe health risk to human beings. It is therefore important to provide effective chelation therapy or decorporation to reduce acute radiation damage, chemical toxicity, and late radiation effects. Speciation governs bioavailability and toxicity of elements and it is a prerequisite tool for the design and success of new ligands or chelating agents. The purpose of this review is to present the state-of-the-art of actinide decorporation within biological media, to recall briefly actinide metabolism, to list the basic constraints of actinide-ligand for development, to describe main tools developed and used for decorporation studies, to review mainly the chelating agents tested for actinides, and finally to conclude on the future trends in this field. (authors)

Chromium, Nickel and Zinc Induced Histopathological Alterations in ...

African Journals Online (AJOL)

Michael Horsfall

fish, Labeo rohita to chlorides of chromium, nickel and zinc for 30 days. However ... toxicants such as salts of heavy metals, acids, organic matter ... nutritional supply becomes excessive. ... action), petrochemicals, and fertilizers and in steam.

Radiopharmaceutical chelates and method of external imaging

International Nuclear Information System (INIS)

1976-01-01

The preparation of the following chemicals is described: chelates of technetium-99m, cobalt-57, gallium-67, gallium-68, indium-111 or indium-113m and a substituted iminodiacetic acid or an 8-hydroxyquinoline useful as a radiopharmaceutical external imaging agent. The compounds described are suitable for intravenous injection, have an excellent in vivo stability and are good organ seekers. Tin(II) choride or other tin(II) compounds are used as chelating agents

Mechanisms of inhibition of zinc-finger transcription factors by selenium compounds ebselen and selenite.

Science.gov (United States)

Larabee, Jason L; Hocker, James R; Hanas, Jay S

2009-03-01

The anti-inflammatory selenium compounds, ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) and selenite, were found to alter the DNA binding mechanisms and structures of cysteine-rich zinc-finger transcription factors. As assayed by DNase I protection, DNA binding by TFIIIA (transcription factor IIIA, prototypical Cys(2)His(2) zinc finger protein), was inhibited by micromolar amounts of ebselen. In a gel shift assay, ebselen inhibited the Cys(2)His(2) zinc finger-containing DNA binding domain (DBD) of the NF-kappaB mediated transcription factor Sp1. Ebselen also inhibited DNA binding by the p50 subunit of the pro-inflammatory Cys-containing NF-kappaB transcription factor. Electrospray ionization mass spectrometry (ESI-MS) was utilized to elucidate mechanisms of chemical interaction between ebselen and a zinc-bound Cys(2)His(2) zinc finger polypeptide modeled after the third finger of Sp1 (Sp1-3). Exposing Sp1-3 to micromolar amounts of ebselen resulted in Zn(2+) release from this peptide and the formation of a disulfide bond by oxidation of zinc finger SH groups, the likely mechanism for DNA binding inhibition. Selenite was shown by ESI-MS to also eject zinc from Sp1-3 as well as induce disulfide bond formation through SH oxidation. The selenite-dependent inhibition/oxidation mechanism differed from that of ebselen by inducing the formation of a stable selenotrisulfide bond. Selenite-induced selenotrisulfide formation was dependent upon the structure of the Cys(2)His(2) zinc finger as alteration in the finger structure enhanced this reaction as well as selenite-dependent zinc release. Ebselen and selenite-dependent inhibition/oxidation of Cys-rich zinc finger proteins, with concomitant release of zinc and finger structural changes, points to mechanisms at the atomic and protein level for selenium-induced alterations in Cys-rich proteins, and possible amelioration of certain inflammatory, neurodegenerative, and oncogenic responses.

Efficacy of the chelating agent CaEDTA in reversing lead-induced changes in behavior.

Science.gov (United States)

Cory-Slechta, D A; Weiss, B

1989-01-01

The chelating agent CaEDTA has been reported to reverse the deficits in intellectual function and performance associated with Pb (lead) exposure in children. However, such studies have not included rigorous controls for the intervention procedures per se. The experiments reported here examined reversibility of performance changes in a rat model based on behavior sensitive to low-level Pb exposure. Rats were exposed to 50 ppm sodium or Pb acetate in drinking water from weaning. Performance maintained under a Fixed-Interval schedule of food reinforcement began at 55 days of age. Following the onset of the characteristic increase in short interresponse times (IRTs) associated with low-level Pb exposure after 35 experimental sessions, Pb treatment was terminated. Animals within both the control and Pb groups were then matched on the basis of performance indices and injected daily for 5 days with either saline, 75 mg/kg or 150 mg/kg CaEDTA. Subsequent changes in F1 performance were monitored for 35-60 sessions. No consistent effects of CaEDTA were detected in control animals. CaEDTA treatment failed to reverse the behavioral effects in Pb-exposed animals. If anything, it tended to further increase the proportion of short IRTs. These data suggest that better controlled clinical studies are warranted to evaluate the efficacy of CaEDTA in reversing Pb-induced behavioral effects before its application for these purposes becomes widespread.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

Kocot, Karina; Zawisza, Beata; Sitko, Rafal

2012-01-01

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. - Highlights: ► Multielement trace analysis using dried-spot technique and dispersive liquid–liquid microextraction. ► Possibility of combination of LPME with EDXRF, LIBS or LA-ICP-MS. ► Comparison of APDC and DDTC as chelating agents.

New fluorescent azo-Schiff base Cu(II) and Zn(II) metal chelates; spectral, structural, electrochemical, photoluminescence and computational studies

Science.gov (United States)

Purtas, Fatih; Sayin, Koray; Ceyhan, Gokhan; Kose, Muhammet; Kurtoglu, Mukerrem

2017-06-01

A new Schiff base containing azo chromophore group obtained by condensation of 2-hydroxy-4-[(E)-phenyldiazenyl]benzaldehyde with 3,4-dimethylaniline (HL) are used for the syntheses of new copper(II) and zinc(II) chelates, [Cu(L)2], and [Zn(L)2], and characterized by physico-chemical and spectroscopic methods such as 1H and 13C NMR, IR, UV.-Vis. and elemental analyses. The solid state structure of the ligand was characterized by single crystal X-ray diffraction study. X-ray diffraction data was then used to calculate the harmonic oscillator model of aromaticity (HOMA) indexes for the rings so as to investigate of enol-imine and keto-amine tautomeric forms in the solid state. The phenol ring C10-C15 shows a considerable deviation from the aromaticity with HOMA value of 0.837 suggesting the shift towards the keto-amine tautomeric form in the solid state. The analytical data show that the metal to ligand ratio in the chelates was found to be 1:2. Theoretical calculations of the possible isomers of the ligand and two metal complexes are performed by using B3LYP method. Electrochemical and photoluminescence properties of the synthesized azo-Schiff bases were also investigated.

Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

Energy Technology Data Exchange (ETDEWEB)

Hunt, F.C.; Maddalena, D.J. (Australian Atomic Energy Commission Research Establishment, Lucas Heights)

The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo.

Rates of cuticular penetration of chelated Fe(III): role of humidity, concentration, adjuvants, temperature, and type of chelate.

Science.gov (United States)

Schönherr, Jörg; Fernández, Victoria; Schreiber, Lukas

2005-06-01

Time courses of cuticular penetration of FeCl3 and Fe(III) complexes of citric acid, EDTA, EDDHA (Sequestrene 138Fe), imidodisuccinic acid (IDHA), and ligninsulfonic acid (Natrel) were studied using astomatous cuticular membranes (CMs) isolated from Populus x canescens leaves. At 100% relative humidity, the Fe(III) chelates disappeared exponentially with time from the surface of the CMs; that is, penetration was a first-order process that can be described using rate constants or half-times of penetration (t(1/2)). Half-times ranged from 20 to 30 h. At 90% humidity, penetration rates were insignificant with the exception of Natrel, for which t(1/2) amounted to 58 h. Rate constants were independent of temperature (15, 25, and 35 degrees C). Permeability decreased with increasing Fe chelate concentration (IDHA and EDTA). At 100% humidity, half-times measured with FeIDHA were 11 h (2 mmol L(-1)), 17 h (10 mmol L(-1)) and 36 h (20 mmol L(-1)), respectively. In the presence of FeEDTA, penetration of CaCl2 was slowed greatly. Half-times for penetration of CaCl2, which were 1.9 h in the absence of FeEDTA, rose to 3.12 h in the presence of an equimolar concentration of EDTA and 13.3 h when the FeEDTA concentration was doubled. Hence, Fe chelates reduced permeability of CMs to CaCl2 and to the Fe chelates themselves. It is suggested that Fe chelates reduced the size of aqueous pores. This view is supported by the fact that rate constants for calcium salts were about 5 times higher than for Fe chelates with the same molecular weights. Adding Tween 20 (5 g L(-1)) as a humectant did not increase permeability to FeIDHA at 90% humidity and below, while addition of glycine betaine did. Penetration of FeCl3 applied at 5 g L(-1) (pH 1.5) was not a first order process as rate constants decreased rapidly with time. Only 2% of the dose penetrated during the first 2 h and less than that in the subsequent 8 h. Recovery was only 70%. This was attributed to the formation of insoluble Fe

Potentials and drawbacks of chelate-enhanced phytoremediation of soils

NARCIS (Netherlands)

Römkens, P.F.A.M.; Bouwman, L.A.; Japenga, J.; Draaisma, C.

2002-01-01

Chelate-enhanced phytoremediation has been proposed as an effective tool for the extraction of heavy metals from soils by plants. However, side-effects related to the addition of chelates, e.g. metal leaching and effects on soil micro-organisms, were usually neglected. Therefore, greenhouse and

Nutrition intervention strategies to combat zinc deficiency in developing countries.

Science.gov (United States)

Gibson, R S; Ferguson, E L

1998-06-01

Widespread zinc deficiency is likely to exist in developing countries where staple diets are predominantly plant based and intakes of animal tissues are low. The severe negative consequences of zinc deficiency on human health in developing countries, however, have only recently been recognized. An integrated approach employing targeted supplementation, fortification and dietary strategies must be used to maximize the likelihood of eliminating zinc deficiency at a national level in developing countries. Supplementation is appropriate only for populations whose zinc status must be improved over a relatively short time period, and when requirements cannot be met from habitual dietary sources. As well, the health system must be capable of providing consistent supply, distribution, delivery and consumption of the zinc supplement to the targeted groups. Uncertainties still exist about the type, frequency, and level of supplemental zinc required for prevention and treatment of zinc deficiency. Salts that are readily absorbed and at levels that will not induce antagonistic nutrient interactions must be used. At a national level, fortification with multiple micronutrients could be a cost effective method for improving micronutrient status, including zinc, provided that a suitable food vehicle which is centrally processed is available. Alternatively, fortification could be targeted for certain high risk groups (e.g. complementary foods for infants). Efforts should be made to develop protected fortificants for zinc, so that potent inhibitors of zinc absorption (e.g. phytate) present either in the food vehicle and/or indigenous meals do not compromise zinc absorption. Fortification does not require any changes in the existing food beliefs and practices for the consumer and, unlike supplementation, does not impose a burden on the health sector. A quality assurance programme is required, however, to ensure the quality of the fortified food product from production to consumption

Mixed and chelated waste test programs with bitumen solidification

International Nuclear Information System (INIS)

Simpson, S.I.; Morris, M.; Vidal, H.

1988-01-01

This paper presents the results of bitumen solidification tests on mixed wastes and chelated wastes. The French Atomic Energy Commission (CEA) performed demonstration tests on radioactive wastes contaminated with chelating agents for Associated Technologies, Inc. (ATI). The chelated wastes were produced and concentrated by Commonwealth Edison Co. as a result of reactor decontamination at Dresden Nuclear Station, Unit 1. Law Engineering in Charlotte, N. C. produced samples and performed tests on simulated heavy metal laden radioactive waste (mixed) to demonstrate the quality of the bituminous product. The simulation is intended to represent waste produced at Oak Ridge National Labs operated by Martin-Marietta

Different photoluminescent properties of binary and ternary europium chelates doped in PMMA

International Nuclear Information System (INIS)

Liu Hongguo; Park, Seongtae; Jang, Kiwan; Zhang Wansong; Seo, Hyo-Jin; Lee, Yong-Ill

2003-01-01

Two kinds of europium-β-diketone chelates, binary Eu(DBM) 3 and ternary Eu(DBM) 3 phen were doped in poly(methyl methacrylate) (PMMA). These chelates show very different photoluminescent (PL) behaviors: the hypersensitive 5 D 0 → 7 F 2 emission bands of Eu(DBM) 3 phen change slightly with the molar ratios, while those of Eu(DBM) 3 change obviously and regularly with the molar ratios. The results of the luminescent lifetimes of 5 D 0 levels show that the binary chelate exists as two kinds of species in the doped systems, and the lifetimes and contents of each species change with the molar ratios, while the ternary chelate exists as one kind of species in the doped systems. X-ray diffraction (XRD) patterns of the binary chelate doped systems give some diffraction peaks that are different from those of pure chelate and change with the molar ratios, indicating new kinds of crystal structures formed, and consequently, the first coordination sphere of Eu 3+ ion changes; while those of the ternary chelate doped systems just show amorphous diffraction halos of the host, indicating that the ternary chelate exist in an amorphous state and disperse well in the host. The FTIR spectra of PMMA also change gradually with increasing the molar ratios of the doped two kinds of chelates, and the XRD patterns show that the amorphous halos of PMMA in the doped systems are different from those of pure PMMA and change with the molar ratios, too, suggesting the interaction between the guest and the host

Localized frustration and binding-induced conformational change in recognition of 5S RNA by TFIIIA zinc finger.

Science.gov (United States)

Tan, Cheng; Li, Wenfei; Wang, Wei

2013-12-19

Protein TFIIIA is composed of nine tandemly arranged Cys2His2 zinc fingers. It can bind either to the 5S RNA gene as a transcription factor or to the 5S RNA transcript as a chaperone. Although structural and biochemical data provided valuable information on the recognition between the TFIIIIA and the 5S DNA/RNA, the involved conformational motions and energetic factors contributing to the binding affinity and specificity remain unclear. In this work, we conducted MD simulations and MM/GBSA calculations to investigate the binding-induced conformational changes in the recognition of the 5S RNA by the central three zinc fingers of TFIIIA and the energetic factors that influence the binding affinity and specificity at an atomistic level. Our results revealed drastic interdomain conformational changes between these three zinc fingers, involving the exposure/burial of several crucial DNA/RNA binding residues, which can be related to the competition between DNA and RNA for the binding of TFIIIA. We also showed that the specific recognition between finger 4/finger 6 and the 5S RNA introduces frustrations to the nonspecific interactions between finger 5 and the 5S RNA, which may be important to achieve optimal binding affinity and specificity.

Serum zinc levels in gestational diabetes

Directory of Open Access Journals (Sweden)

Rahimi Sharbaf F

2008-12-01

Full Text Available "nBackground: Maternal zinc deficiency during pregnancy has been related to adverse pregnancy outcomes. Most studies in which pregnant women have been supplemented with zinc to examine its effects on the outcome of the pregnancy have been carried out in industrialized countries and the results have been inconclusive. It has been shown that women with gestational diabetes (GDM have lower serum zinc levels than healthy pregnant women, and higher rates of macrosomia. Zinc is required for normal glucose metabolism, and strengthens the insulin-induced transportation of glucose into cells by its effect on the insulin signaling pathway. The purpose of this study was to assess the serum zinc levels of GDM patients and evaluate the effect of zinc supplementation. "nMethods: In the first stage of this prospective controlled study, we enrolled 70 women who were 24-28 weeks pregnant at the Prenatal Care Center of Mirza Kochak Khan Hospital, Tehran, Iran. The serum zinc level of each subject was determined. In the second stage, among these 70 subjects, the diabetics receiving insulin were divided into two groups, only one of which received a zinc supplement and the other group was the control group. Birth weight of neonates and insulin dosages were recorded. "nResults: The mean serum zinc level in the GDM group was lower than that of the control group (94.83 vs. 103.49mg/dl, respectively and the mean birth weight of neonates from the GDM women who received the zinc supplement was lower than that of the control group (3849g vs. 4136g. The rate of macrosomia was lower in the zinc supplemented group (20% vs. 53%. The mean of increase of insulin after receiving the zinc supplement was lower (8.4u vs. 13.53. "nConclusion: Maternal insulin resistance is associated with the accumulation of maternal fat tissue during early stages of pregnancy and greater fetoplacental nutrient availability in later stages, when 70% of fetal growth occurs, resulting in macrosomia. In

Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

International Nuclear Information System (INIS)

Hunt, F.C.; Maddalena, D.J.

1982-01-01

The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo. (U.K.)

Antioxidant, Iron-chelating and Anti-glucosidase Activities of Typha ...

African Journals Online (AJOL)

Iron chelating activity was assessed using a ferrozine-based assay. Anti- glucosidase activity was determined using 4-nitrophenyl ... flavonoid (TF) content was determined based an aluminum chloride colorimetric assay [6]. TF content was ..... Dietary iron restriction or iron chelation protects from diabetes and loss of β-cell.

Dietary phytate, zinc and hidden zinc deficiency.

Science.gov (United States)

Sandstead, Harold H; Freeland-Graves, Jeanne H

2014-10-01

Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

Science.gov (United States)

Foster, Meika; Samman, Samir

2012-01-01

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

Effects of peroral supplementation of different forms of zinc on the ruminal mucosa of goat kids – a morphometric study

Directory of Open Access Journals (Sweden)

Julius Černík

2013-01-01

Full Text Available The aim of the study was to identify the effect of supplementation of various forms of zinc on the ruminal mucosa and dimensions of ruminal papillae in 6-month-old goat kids. The experimental period lasted from weaning to slaughter (4 months. All 20 kids divided into four groups of five animals, were fed with the same feeding dose, which was different only in the quantity and form of zinc. Control group was without additional zinc supplementation (group A, the other groups were supplemented with zinc in the form of ZnO (group B, zinc in the form of chelate (group C and zinc in the form of lactate (group D. Samples for histopathological and morphometric examination were collected after the slaughter of all animals from the bottom of saccus ruminis ventralis everytime from the same place. Significant differences were reported within the comparison of the length of ruminal papillae between groups B and C (P = 0.026 and B and D (P = 0.040, within the comparison of the width of ruminal papillae between groups A and D (P = 0.020 and within the comparison of the intensity of keratinisation of the mucosa of ruminal papillae between groups A and B (P = 0.034, A and C (P = 0.038 and A and D (P = 0.001. Histopathological and morphometric examination of ruminal mucosa indicated that the ruminal papillae of kids supplemented with zinc in the form of ZnO (group B were better developed compared to the other groups. This result indicates better utilisation of the supplemented zinc in the form of ZnO.

Olivine-type cathode for rechargeable batteries: Role of chelating agents

International Nuclear Information System (INIS)

Kandhasamy, Sathiyaraj; Singh, Pritam; Thurgate, Stephen; Ionescu, Mihail; Appadoo, Dominique; Minakshi, Manickam

2012-01-01

Highlights: ► Olivine powder was synthesized by sol–gel method using a range of chelating agents. ► Role of chelating agents in olivine cathode was investigated for battery application. ► Battery was fabricated with olivine cathode, Zn anode and aqueous electrolyte. ► Synergetic effect of additives (CA + TEA + PVP) led to improved storage capacity. - Abstract: Olivine (LiCo 1/3 Mn 1/3 Ni 1/3 PO 4 ) powders were synthesized at 550–600 °C for 6 h in air by a sol–gel method using multiple chelating agents and used as a cathode material for rechargeable batteries. Range of chelating agents like a weak organic acid (citric acid – CA), emulsifier (triethanolamine – TEA) and non-ionic surfactant (polyvinylpyrrolidone – PVP) in sol–gel wet chemical synthesis were used. The dependence of the physicochemical properties of the olivine powders such as particle size, morphology, structural bonding and crystallinity on the chelating agent was extensively investigated. Among the chelating agents used, unique cycling behavior (75 mAh/g after 25 cycles) is observed for the PVP assisted olivine. This is due to volumetric change in trapped organic layer for first few cycles. The trapped organic species in the electrode–electrolyte interface enhances the rate of lithium ion diffusion with better capacity retention. In contrast, CA and TEA showed a gradual capacity fade of 30 and 38 mAh/g respectively after multiple cycles. The combination of all the three mixed chelating agents showed an excellent electrochemical behavior of 100 mAh/g after multiple cycles and the synergistic effect of these agents are discussed.

Zinc-induced hemolytic anemia caused by ingestion of pennies by a pup

International Nuclear Information System (INIS)

Latimer, K.S.; Jain, A.V.; Inglesby, H.B.; Clarkson, W.D.; Johnson, G.B.

1989-01-01

A 4-month-old Pomeranian pup was examined because of anorexia, salivation, and persistent vomiting. Initial laboratory testing revealed marked hemolytic anemia with spherocytosis. Survey abdominal radiography revealed 4 metal objects which, when removed by gastrotomy, were identified as pennies. Of 4 pennies, 3 were minted since 1983 and were heavily pitted over the surface and rim. Partially digested pennies were composed of a copper-plated high zinc concentration alloy. Further laboratory testing indicated a marked increase in serum zinc concentration in the pup (28.8 mg/L), confirming metal toxicosis. Serum zinc concentrations decreased during recovery

Symptomatic acquired zinc deficiency in at-risk premature infants: high dose preventive supplementation is necessary.

Science.gov (United States)

Barbarot, Sébastien; Chantier, Emilie; Kuster, Alice; Hello, Muriel; Roze, Jean-Christophe; Blouin, Eric; Stalder, Jean-François

2010-01-01

Zinc is a cofactor for several enzymes involved in many metabolisms. Zinc deficiency induces various disorders such as acrodermatitis enteropathica, either inherited or acquired. We report three cases of premature infants (24-31 wks gestational age) with low birthweight (650 to 940 g) and enteropathy, two of whom presented with necrotizing enterocolitis. All infants were fed by total parenteral nutrition. At a chronological age ranging from 73 to 80 days, all infants developed a periorificial dermatitis. Before the onset of the first signs, they had received zinc supplementation ranging from 146% to 195% of the recommended dose (400 microg/kg/day). Increased zinc supplementation over a course of 6-18 days induced a complete resolution of symptoms in all cases. No abnormality in the neurologic examination and no recurrence were observed at the end of the zinc treatment. Low birthweight premature infants with enteropathy on total parenteral nutrition are at risk of developing zinc deficiency. The usual recommended zinc supplementation is probably insufficient for those infants. A delay in the diagnosis of zinc deficiency may lead to severe complications.

Effects of Chronic and Acute Zinc Supplementation on Myocardial Ischemia-Reperfusion Injury in Rats.

Science.gov (United States)

Ozyıldırım, Serhan; Baltaci, Abdulkerim Kasim; Sahna, Engin; Mogulkoc, Rasim

2017-07-01

The present study aims to explore the effects of chronic and acute zinc sulfate supplementation on myocardial ischemia-reperfusion injury in rats. The study registered 50 adult male rats which were divided into five groups in equal numbers as follows: group 1, normal control; group 2, sham; group 3, myocardial ischemia reperfusion (My/IR): the group which was fed on a normal diet and in which myocardial I/R was induced; group 4, myocardial ischemia reperfusion + chronic zinc: (5 mg/kg i.p. zinc sulfate for 15 days); and group 5, myocardial ischemia reperfusion + acute zinc: the group which was administered 15 mg/kg i.p. zinc sulfate an hour before the operation and in which myocardial I/R was induced. The collected blood and cardiac tissue samples were analyzed using spectrophotometric method to determine levels of MDA, as an indicator of tissue injury, and GSH, as an indicator of antioxidant activity. The highest plasma and heart tissue MDA levels were measured in group 3 (p zinc administration and markedly by chronic zinc supplementation.

Metal-chelating active packaging film enhances lysozyme inhibition of Listeria monocytogenes.

Science.gov (United States)

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

2014-07-01

Several studies have demonstrated that metal chelators enhance the antimicrobial activity of lysozyme. This study examined the effect of metal-chelating active packaging film on the antimicrobial activity of lysozyme against Listeria monocytogenes. Polypropylene films were surface modified by photoinitiated graft polymerization of acrylic acid (PP-g-PAA) from the food contact surface of the films to impart chelating activity based on electrostatic interactions. PP-g-PAA exhibited a carboxylic acid density of 113 ± 5.4 nmol cm(-2) and an iron chelating activity of 53.7 ± 9.8 nmol cm(-2). The antimicrobial interaction of lysozyme and PP-g-PAA depended on growth media composition. PP-g-PAA hindered lysozyme activity at low ionic strength (2.48-log increase at 64.4 mM total ionic strength) and enhanced lysozyme activity at moderate ionic strength (5.22-log reduction at 120 mM total ionic strength). These data support the hypothesis that at neutral pH, synergy between carboxylate metal-chelating films (pKa(bulk) 6.45) and lysozyme (pI 11.35) is optimal in solutions of moderate to high ionic strength to minimize undesirable charge interactions, such as lysozyme absorption onto film. These findings suggest that active packaging, which chelates metal ions based on ligand-specific interactions, in contrast to electrostatic interactions, may improve antimicrobial synergy. This work demonstrates the potential application of metal-chelating active packaging films to enhance the antimicrobial activity of membrane-disrupting antimicrobials, such as lysozyme.

[Approach to the relationship between the changes of the content of free zinc in hippocampus and ischemic neuronal damage].

Science.gov (United States)

Zhou, Zhu-Juan; Zheng, Jian; He, Ying

2002-08-01

To make approach to the relationship between the changes of free zinc and ischemic neuronal damage in hippocampus after forebrain ischemia/reperfusion. The models of forebrain ischemia/reperfusion were established in rats. The contents of free Zn2+ were measured by TSQ fluorescence method. The Zn2+ chelator (CaEDTA) was injected into lateral ventricles in order to evaluate the effect of free Zn2+ on ischemic neuronal damage. (1) Zn2+ fluorescence in the hilus of dentate gyrus, CA3 region and the stratum radiatum and stratum oriens of CA1 decreased slightly at forty-eight hours after reperfusion. From seventy-two hours to ninety-six hour after reperfusion, the decreased fluorescence gradually returned to the normal level, but some fluorescence dots were found in pyramidal neurons of CA1 and the hilus of dentate gyrus. Seven days after reperfusion, all the changes of the fluorescence almost recovered. (2) The cell membrane-impermeable Zn2+ chelator CaEDTA could reduce the intracellular concentration of free Zn2+ and reduced neuronal damage after forebrain ischemia/reperfusion. (1) The synaptic vesicle Zn2+ released and then translocated into postsynaptic neurons after forebrain ischemia/reperfusion and played a role in ischemic neuronal damage. (2) The cell membrane-impermeable chelator CaEDTA could provide neuroprotection.

Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

Science.gov (United States)

Oluwole, F S; Onwuchekwa, C

2016-09-01

Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

Science.gov (United States)

Moniz, T; Leite, A; Silva, T; Gameiro, P; Gomes, M S; de Castro, B; Rangel, M

2017-10-01

We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore. Copyright © 2017 Elsevier Inc. All rights reserved.

Zinc deprivation of methanol fed anaerobic granular sludge bioreactors

Science.gov (United States)

Fermoso, Fernando G.; Collins, Gavin; Bartacek, Jan

2008-01-01

The effect of omitting zinc from the influent of mesophilic (30 °C) methanol fed upflow anaerobic sludge bed (UASB) reactors, and latter zinc supplementation to the influent to counteract the deprivation, was investigated by coupling the UASB reactor performance to the microbial ecology of the bioreactor sludge. Limitation of the specific methanogenic activity (SMA) on methanol due to the absence of zinc from the influent developed after 137 days of operation. At that day, the SMA in medium with a complete trace metal solution except Zn was 3.4 g CH4-COD g VSS−1 day−1, compared to 4.2 g CH4-COD g VSS−1 day−1 in a medium with a complete (including zinc) trace metal solution. The methanol removal capacity during these 137 days was 99% and no volatile fatty acids accumulated. Two UASB reactors, inoculated with the zinc-deprived sludge, were operated to study restoration of the zinc limitation by zinc supplementation to the bioreactor influent. In a first reactor, no changes to the operational conditions were made. This resulted in methanol accumulation in the reactor effluent after 12 days of operation, which subsequently induced acetogenic activity 5 days after the methanol accumulation started. Methanogenesis could not be recovered by the continuous addition of 0.5 μM ZnCl2 to the reactor for 13 days. In the second reactor, 0.5 μM ZnCl2 was added from its start-up. Although the reactor stayed 10 days longer methanogenically than the reactor operated without zinc, methanol accumulation was observed in this reactor (up to 1.1 g COD-MeOH L−1) as well. This study shows that zinc limitation can induce failure of methanol fed UASB reactors due to acidification, which cannot be restored by resuming the continuous supply of the deprived metal. PMID:18283507

Theoretical analysis of the influence of chelate-ring size and vicinal effects on electronic circular dichroism spectra of cobalt(III) EDDA-type complexes.

Science.gov (United States)

Wang, Ai; Wang, Yuekui; Jia, Jie; Feng, Lixia; Zhang, Chunxia; Liu, Linlin

2013-06-20

To assess the contributions of configurational and vicinal effects as well as chelate-ring size to rotational strengths, the geometries of a series of cobalt(III) complexes [Co(EDDA-type)(L)](±) with the tetradentate EDDA-type ligands, EDDA (ethylenediamine-N,N'-diacetate), DMEDDA (N,N'-dimethylethylenediamine-N,N'-diacetate), DEEDDA (N,N'-diethylethylenediamine-N,N'-diacetate), and a bidentate ancillary ligand L (L = ethylenediamine, oxalate, carbonate, (S)-alanine, and malonate) in aqueous solution have been optimized at the DFT/B3LYP/6-311++G(2d,p) level of theory. Based on the optimized geometries, the excitation energies and oscillator and rotational strengths have been calculated using the time-dependent density functional theory (TDDFT) method with the same functional and basis set. The calculated circular dichroism (CD) curves are in excellent agreement with the observed ones except for some small red or blue shifts in peak wavelengths. For the influence of chelate-ring size of the bidentate ligands on the CD intensities, a qualitative analysis together with the quantitative TDDFT calculation reveal that it depends on the symmetry of the cobalt-EDDA backbone. For the s-cis-isomers, the influence is negligible due to the perturbation is symmetric. For the uns-cis-isomers, the perturbation is unsymmetric. Since a small ring size means a large perturbation, this leads to the integral CD intensities decreasing with increasing the chelate ring size. The vicinal effects of asymmetric nitrogens incorporate both the substitutent effects and conformational relaxation effects, with the former being dominant. By analyzing the contributions of chiral arrays to rotational strengths, we found that the part of contributions dominated by the S-type chiral nitrogens could be considered as a good measure for the vicinal effects of chiral nitrogens. In addition, we found that the twist form (δ/λ) of the backbone ethylenediamine ring (E-ring) of the coordinated EDDA

Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.

Science.gov (United States)

Maywald, Martina; Rink, Lothar

2017-08-01

The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [ 3 H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4 + CD25 + Foxp3 + and CD4 + CD25 + CTLA-4 + T cells (p zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

Interaction of chelating agents with cadmium in mice and rats

International Nuclear Information System (INIS)

Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, 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 CdCl 2 and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl 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 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

Bone marrow and chelatable iron in patients with protein energy ...

African Journals Online (AJOL)

chelatable iron is present and is excreted in the urine of children with kwashiorkor ... venous blood sample was drawn for routine biochemical and haematological .... storage.l.1:m In response to chelation, the kwashiorkor children excrete large ...

In vitro and in vivo evaluation of potential aluminum chelators.

Science.gov (United States)

Graff, L; Muller, G; Burnel, D

1995-10-01

The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.

Modulations of anisotropic optical transmission on alumina-doped zinc oxide surface by femtosecond laser induced ripples

Science.gov (United States)

Lu, Yanhui; Jiang, Lan; Sun, Jingya; Cao, Qiang; Wang, Qingsong; Han, Weina; Lu, Yongfeng

2018-04-01

This study demonstrated that femtosecond-laser-induced ripples on an alumina-doped zinc oxide (AZO) film with space intervals of approximately 340 and 660 nm exhibit modulations of anisotropic optical transmission. At low laser fluence, ripples can not affect the original absorption peak of AZO film, but at higher laser fluence, the absorption peak of AZO film is disappeared due to the modulation by femtosecond laser induced ripples. Moreover, the relationship between the anisotropic optical transmission and the features of nanostructures is discussed. Ripples with a space interval of approximately 660 nm have a higher ability to block light than nanostructures with a space interval of approximately 340 nm. These observations indicate that anisotropic optical transmission has potential applications in the field of optoelectronics.

Selectivity in extraction of copper and indium with chelate extractants

International Nuclear Information System (INIS)

Zivkovic, D.

2003-01-01

Simultaneous extraction of copper and indium with chelate extractants (LIX84 and D2E11PA) was described. Stechiometry of metal-organic complexes examined using the method of equimolar ratios resulted in CuR 2 and InR 3 forms of hydrophobic extracting species. A linear correlation was obtained between logarithm of distribution coefficients and chelate agents and pH, respectively. Selectivity is generally higher with higher concentrations of chelate agents in the organic phase, and is decreased with increase of concentration of hydrogen ions in feeding phase. (Original)

Elimination of zinc-65 from the brain under kainate-induced seizures.

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Takeda, Atsushi; Hirate, Maki; Oku, Naoto

2004-04-01

On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

Zinc piracy as a mechanism of Neisseria meningitidis for evasion of nutritional immunity.

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Michiel Stork

2013-10-01

Full Text Available The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment. Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins. However, diffusion can only satisfy the growth requirements if the extracellular concentration of the nutrients is high. In the vertebrate host, the sequestration of essential nutrient metals is an important defense mechanism that limits the growth of invading pathogens, a process known as "nutritional immunity." The acquisition of scarce nutrients from the environment is mediated by receptors in the outer membrane in an energy-requiring process. Most characterized receptors are involved in the acquisition of iron. In this study, we characterized a hitherto unknown receptor from Neisseria meningitidis, a causative agent of sepsis and meningitis. Expression of this receptor, designated CbpA, is induced when the bacteria are grown under zinc limitation. We demonstrate that CbpA functions as a receptor for calprotectin, a protein that is massively produced by neutrophils and other cells and that has been shown to limit bacterial growth by chelating Zn²⁺ and Mn²⁺ ions. Expression of CbpA enables N. meningitidis to survive and propagate in the presence of calprotectin and to use calprotectin as a zinc source. Besides CbpA, also the TonB protein, which couples energy of the proton gradient across the inner membrane to receptor-mediated transport across the outer membrane, is required for the process. CbpA was found to be expressed in all N. meningitidis strains examined, consistent with a vital role for the protein when the bacteria reside in the host. Together, our results demonstrate that N. meningitidis is able to subvert an important defense mechanism of the human host and to utilize calprotectin to promote its growth.

ELECTED PROBLEMS RELATED TO ENVIRONMENTAL HEAVY METALS EXPOSURE AND CHELATION THERAPY

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Anna Skoczyńska

2010-09-01

Full Text Available Background: Exposure to heavy metals leads to functional and metabolic disturbances and many of them are included in pathogenesis of common diseases (arterial hypertension, atherosclerosis, neurodegenerative processes. In this context new therapeutic and prophylactic strategies are necessary. Patients diagnosed with chronic heavy metals intoxication usually require chelation to increase mobilisation of metals from tissues and elimination of them via urine. Acute poisoning with toxic metal may be difficult to diagnosis, especially in case of accidental intoxication or suicidal intention. Patients also require chelation after causative factor is identified. Objectives: To describe some problems connected with toxicity of metals poisoning and to review pharmacologic therapies that could have a role in poisoning with metals. Methods: A review of the literature was carried out and expert opinion expressed. Results/conclusion: Chelation is a common therapy in case of poisoning with toxic metals but it is satisfied only partially. A combined therapy with structurally different chelators or long-term acting chelators could become viable alternatives in the future. A combined therapy with an antioxidant plus chelator may be a good choice in patients chronically poisoned with metals. Exposure to lead should be taken into account during estimation of global cardiovascular risk.

EDTA chelation therapy for cardiovascular disease: a systematic review

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Wu Ping

2005-11-01

Full Text Available Abstract Background Numerous practitioners of both conventional and complementary and alternative medicine throughout North America and Europe claim that chelation therapy with EDTA is an effective means to both control and treat cardiovascular disease. These claims are controversial, and several randomized controlled trials have been completed dealing with this topic. To address this issue we conducted a systematic review to evaluate the best available evidence for the use of EDTA chelation therapy in the treatment of cardiovascular disease. Methods We conducted a systematic review of 7 databases from inception to May 2005. Hand searches were conducted in review articles and in any of the trials found. Experts in the field were contacted and registries of clinical trials were searched for unpublished data. To be included in the final systematic review, the studies had to be randomized controlled clinical trials. Results A total of seven articles were found assessing EDTA chelation for the treatment of cardiovascular disease. Two of these articles were subgroup analyses of one RCT that looked at different clinical outcomes. Of the remaining five studies, two smaller studies found a beneficial effect whereas the other three exhibited no benefit for cardiovascular disease from the use of EDTA chelation therapy. Adverse effects were rare but those of note included a few cases of hypocalcemia and a single case of increased creatinine in a patient on the EDTA intervention. Conclusion The best available evidence does not support the therapeutic use of EDTA chelation therapy in the treatment of cardiovascular disease. Although not considered to be a highly invasive or harmful therapy, it is possible that the use of EDTA chelation therapy in lieu of proven therapy may result in causing indirect harm to the patient.

Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model.

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Kitamura, Youji; Iida, Yasuhiko; Abe, Jun; Ueda, Masashi; Mifune, Masaki; Kasuya, Fumiyo; Ohta, Masayuki; Igarashi, Kazuo; Saito, Yutaka; Saji, Hideo

2006-02-01

In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 microM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 microM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.

Chelation Treatment for Autism Spectrum Disorders: A Systematic Review

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Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin

2013-01-01

Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…

Copper chelators: chemical properties and bio-medical applications.

Science.gov (United States)

Tegoni, M; Valensin, D; Toso, L; Remelli, M

2014-01-01

Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.

The zinc dyshomeostasis hypothesis of Alzheimer's disease.

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Travis J A Craddock

Full Text Available Alzheimer's disease (AD is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ, intracellular neurofibrillary tangles (NFTs composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau, and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1 used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2 performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3 used metallomic imaging mass spectrometry (MIMS to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of

The zinc dyshomeostasis hypothesis of Alzheimer's disease.

Science.gov (United States)

Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized

Bis-phosphonate sequestering agents. Synthesis and preliminary evaluation for in vitro and in vivo uranium(VI) chelation

Energy Technology Data Exchange (ETDEWEB)

Sawicki, M.; Lecercle, D.; Taran, F. [CEA Saclay, IBiTecS, Serv Chim Bioorgan et Marquage, F-91191 Gif Sur Yvette (France); Grillon, G.; Le Gall, B.; Serandour, A.L.; Poncy, J.L. [CEA, DSV, DRR, Lab Radiotoxicol, F-91680 Bruyeres Le Chatel (France); Bailly, T.; Burgada, R.; Lecouvey, M.; Challeix, V. [CNRS, Lab Chim Struct Biomol, UMR 7033, F-93017 Bobigny (France); Leydier, A.; Pellet-Rostaing, S. [Univ Lyon 1, ICBMS, UMR 5246, Lab Catalyse et Synth Organ, F-69622 Villeurbanne (France); Ansoborlo, E. [CEA, DEN, DRCP, CETAMA, VRH Marcoule, F-30207 Bagnols Sur Ceze (France)

2008-07-01

A library of bis-phosphonate-based ligands was prepared using solution-phase parallel synthesis and tested for its uranium-binding properties. With the help of a screening method, based on a chromo-phoric complex displacement procedure, 23 dipodal and tripodal chelates bearing bis-phosphonate chelating functions were found to display very high affinity for the uranyl ion and were selected for evaluation of their in vivo uranyl-removal efficacy. Among them, 11 ligands induced a huge modification of the uranyl biodistribution by deviating the metal from kidney and bones to liver. Among the other ligands, the most potent was the dipodal bis-phosphonate 3C which reduced the retention of uranyl and increased its excretion by around 10% of the injected metal. (authors)

Shock-induced fast reactions of zinc nanoparticles and RDX

International Nuclear Information System (INIS)

Xue Mian; Wu Jinghe; Ye Song; Yang Xiangdong; Hu Dong; Wang Yanping; Zhu Wenjun; Li Chengbing

2008-01-01

Fast reactions of zinc nanoparticles and RDX were investigated in normal incident shock waves. The emergence time and emission spectra intensity of partial products such as NO 2 , H, C 2 , O, CO, CH 2 O, CO 2 , H 2 O and ZnO were observed by a TDS5054 oscilloscope. The results indicate that NO 2 appears first in each experiment, which is in agreement with the theoretical results. The addition of zinc nanoparticles to RDX can not only shorten the ignition delay time by 20% but also double the shockwave diffusion velocity to 2180 ± 50 m s -1 and triple the temperature to 2020 ± 60 K. The emergence time of products shortens by around 10-40% and the emission spectra intensity of H 2 O and CH 2 O rises by about three times and one times, respectively. CO 2 , H 2 O and O 2 in various concentrations were introduced into the zinc-RDX reaction, respectively, which indicate that O 2 made the ignition delay time shorten by over 30%, the effect of H 2 O was not prominent while CO 2 made the ignition delay time lag by around 30%. The results indicate that the Zn-O 2 reaction mainly occurs in O 2 , CO 2 and H 2 O

A review of pitfalls and progress in chelation treatment of metal poisonings.

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Andersen, Ole; Aaseth, Jan

2016-12-01

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Suplementação com zinco pode recuperar apetite para refeições de sal Zinc supplementation may recover taste for salt meals

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Dioclécio Campos Jr

2004-02-01

Full Text Available OBJETIVO: Avaliar o efeito do zinco em crianças de 8 meses a 5 anos de idade com falta de apetite para refeições de sal. POPULAÇÃO E MÉTODOS: Estudo duplo-cego com placebo. Dois grupos de crianças apresentando recusa a alimentos de sal foram acompanhados durante 6 meses. As crianças do primeiro grupo receberam 1 mg/kg/dia de zinco sob forma de quelato, durante três meses, enquanto as do segundo grupo receberam uma solução placebo durante o mesmo período. Os dois grupos eram semelhantes quanto a idade, sexo, peso, duração do aleitamento materno, idade de desmame e exames hetamatológicos e bioquímicos. A resposta das crianças ao tratamento foi informada em questionário preenchido regularmente pelas mães. RESULTADOS: 17/20 (85% das crianças que receberam zinco e 10/20 (50% das que receberam placebo recuperaram o apetite para refeições de sal. A diferença foi estatisticamente significativa para p OBJECTIVE: To evaluate the effect of zinc on the appetite for salt foods in children aged 8 months to 5 years. METHOD: Double-blind, placebo-controlled study. Two groups of 20 children refusing to eat salt foods were followed during six months. The children in the first group received zinc chelate 1 mg/kg daily for three months. The second group received a placebo solution. The two groups were similar in terms of age, sex, weight, duration of breastfeeding, age at weaning, biochemical and hematological data. The response of children to treatment was informed by their mothers. RESULTS: 17/20 (85% of the children receiving zinc chelate and 10/20 (50% of the children receiving placebo improved their appetite for salt foods. The difference was statistically significant (p < 0.05, chi-square test. CONCLUSION: Zinc supplementation may improve the acceptance of salt foods by children.

Aflatoxin B1 Induced Systemic Toxicity in Poultry and Rescue Effects of Selenium and Zinc.

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Mughal, Muhammad Jameel; Peng, Xi; Kamboh, Asghar Ali; Zhou, Yi; Fang, Jing

2017-08-01

Among many challenges, exposure to aflatoxins, particularly aflatoxin B 1 (AFB 1 ), is one of the major concerns in poultry industry. AFB 1 intoxication results in decreased meat/egg production, hepatotoxicity, nephrotoxicity, disturbance in gastrointestinal tract (GIT) and reproduction, immune suppression, and increased disease susceptibility. Selenium (Se) and zinc (Zn), in dietary supplementation, offer easy, cost-effective, and efficient ways to neutralize the toxic effect of AFB 1 . In the current review, we discussed the impact of AFB 1 on poultry industry, its biotransformation, and organ-specific noxious effects, along with the action mechanism of AFB 1 -induced toxicity. Moreover, we explained the biological and detoxifying roles of Se and Zn in avian species as well as the protection mechanism of these two trace elements. Ultimately, we discussed the use of Se and Zn supplementation against AFB 1 -induced toxicity in poultry birds.

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

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

2010-06-01

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

Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

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Yi Ting

2012-11-01

Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

[Improvement in zinc nutrition due to zinc transporter-targeting strategy].

Science.gov (United States)

Kambe, Taiho

2016-07-01

Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

Interaction of chelating agents with cadmium in mice and rats.

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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

Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

International Nuclear Information System (INIS)

Boeckner, L.S.; Kies, C.

1986-01-01

The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10 -6 was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study

Comprehensive analyses of DNA methylation profile, regulation on flowering, and seed mineral accumulation in Arabidopsis thaliana in response to zinc deficiency

OpenAIRE

Chen Xiaochao

2016-01-01

Zinc (Zn) is an essential micronutrient for plant growth and development, which plays important roles in DNA binding, metabolic, catalytic and transcriptional regulator activities. However, Zn deficiency is a worldwide problem due to its limited bioavailability in soils in many agricultural areas, often as a result of high CaCO3 content and high pH. In addition, phytic acid is able to strongly chelate cations, such as Zn2+, Fe2+, Ca2+ and Mg2+ to form the phytate salts. Phytate cannot be dige...

Proton microprobe analysis of zinc in skeletal tissues. [Proton induced x-ray emission analysis

Energy Technology Data Exchange (ETDEWEB)

Doty, S B; Jones, K W; Kraner, H W; Shroy, R E; Hanson, A L

1980-06-01

A proton microprobe with windowless exit port was used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage.

Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

Science.gov (United States)

Nazarizadeh, Ali; Asri-Rezaie, Siamak

2016-08-01

In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

OpenAIRE

Liren Fan; Jiqing Song; Wenbo Bai; Shengping Wang; Ming Zeng; Xiaoming Li; Yang Zhou; Haifeng Li; Haiwei Lu

2016-01-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shel...

Zinc absorption in experimental osmotic diarrhea: effect of long-chain fatty acids.

Science.gov (United States)

Lee, S Y; Wapnir, R A

1993-03-01

The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.

The effect of inorganic and organic form of zinc on digestibility of nutrients in dairy cows in three stages of reproductive cycle

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Marie Balabánová

2011-01-01

Full Text Available The aim of our experiment was to compare the effect of feeding inorganic and organic forms of zinc in premix on the coefficient of digestibility of nutrients in the feeding ration for cows in three stages of reproductive cycle – 14 d before calving and 30 and 60 d after calving. The experiment was carried out on 19 Holstein cows that were divided into two groups. A control group of nine cows designated as “Inorganic zinc form” (IZF was fed a diet supplemented with mineral premix containing inorganic form of zinc (ZnO. An experimental group of ten cows designated as “Organic zinc form” (OZF had zinc oxide replaced with zinc fixed to methionine (Khei-chelate Zn powder 15% by Kheiron. The experiment was divided into three periods - the first period lasted from 14th day before calving until 2nd day after calving, the second period lasted from 3rd day to 30th day after calving and the third period lasted from 31st day to 60th day after calving. Cows were fed the diet based on maize silage, lucerne haylage, sugar beet pulp silage, grass or lucerne hay and concentrate containing premix with either inorganic or organic zinc form. During the experiment samples of feeding ration and faeces were taken in 3 intervals, it si on 14th day before calving, on 30th day and on 60th day after calving to determine nutrients content. Digestibility of nutrients was calculated using indicator method (ash insoluble in 3 M HCl.After feeding organic forms of zinc a tendency to higher digestibility of crude protein, fat, crude fiber, nitrogen-free extracts, ash and zinc was observed in cows regardless of stage of reproductive cycle. The digestibility of the zinc and fiber were the most increased. Digestibility of zinc in OZF on 14th day before calving was higher than in IZF (P < 0.05. Feeding of organic zinc forms had downward effect only on the digestibility of copper.

Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

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Layasadat Khorsandi

2016-06-01

Full Text Available Background: Zinc oxide nanoparticles (NZnO are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA and superoxide dismutase (SOD and glutathione peroxidase (GPx activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL method. Results: NZnO induced a significant increase in plasma AST (2.8-fold, ALT (2.7-fold and ALP (1.97-fold activity in comparison to the control group (p<0.01. NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01. Pre-treatment of Cur significantly reduced lipid peroxidation (39%, increased SOD (156% and GPx (26% activities, and attenuated ALT (47%, AST (41% and ALP (30% activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05. Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

f-Element Ion Chelation in Highly Basic Media - Final Report

International Nuclear Information System (INIS)

Paine, R.T.

2000-01-01

A large body of data has been collected over the last fifty years on the chemical behavior of f-element ions. The ions undergo rapid hydrolysis reactions in neutral or basic aqueous solutions that produce poorly understood oxide-hydroxide species; therefore, most of the fundamental f-element solution chemistry has allowed synthetic and separations chemists to rationally design advanced organic chelating ligands useful for highly selective partitioning and separation of f-element ions from complex acidic solution matrices. These ligands and new examples under development allow for the safe use and treatment of solutions containing highly radioactive species. This DOE/EMSP project was undertaken to address the following fundamental objectives: (1) study the chemical speciation of Sr and lanthanide (Ln) ions in basic aqueous media containing classical counter anions found in waste matrices; (2) prepare pyridine N-oxide phosphonates and phosphonic acids that might act as selective chelator s for Ln ions in model basic pH waste streams; (3) study the binding of the new chelators toward Ln ions and (4) examine the utility of the chelators as decontamination and dissolution agents under basic solution conditions. The project has been successful in attacking selected aspects of the very difficult problems associated with basic pH solution f-element waste chemistry. In particular, the project has (1) shed additional light on the initial stages of Ln ion sol-gel-precipitate formulation under basic solution conditions; (2) generated new families of pyridine phosphonic acid chelators; (3) characterized the function of the chelators and (4) examined their utility as oxide-hydroxide dissolution agents. These findings have contributed significantly to an improved understanding of the behavior of Ln ions in basic media containing anions found in typical waste sludges as well as to the development of sludge dissolution agents. The new chelating reagents are easily made and could be

Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

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Thomas L. Mindt

2013-03-01

Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

Shock-induced fast reactions of zinc nanoparticles and RDX

Energy Technology Data Exchange (ETDEWEB)

Xue Mian; Wu Jinghe; Ye Song; Yang Xiangdong [Institute of Atomic and Molecular Physics, Sichuan University, Chengdu 610065 (China); Hu Dong; Wang Yanping; Zhu Wenjun; Li Chengbing [National Key Laboratory for Shock Wave and Detonation Physics Research, Institute of Fluid Physics, CAEP, Mianyang 621900 (China)], E-mail: mi-anxue@163.com

2008-02-21

Fast reactions of zinc nanoparticles and RDX were investigated in normal incident shock waves. The emergence time and emission spectra intensity of partial products such as NO{sub 2}, H, C{sub 2}, O, CO, CH{sub 2}O, CO{sub 2}, H{sub 2}O and ZnO were observed by a TDS5054 oscilloscope. The results indicate that NO{sub 2} appears first in each experiment, which is in agreement with the theoretical results. The addition of zinc nanoparticles to RDX can not only shorten the ignition delay time by 20% but also double the shockwave diffusion velocity to 2180 {+-} 50 m s{sup -1} and triple the temperature to 2020 {+-} 60 K. The emergence time of products shortens by around 10-40% and the emission spectra intensity of H{sub 2}O and CH{sub 2}O rises by about three times and one times, respectively. CO{sub 2}, H{sub 2}O and O{sub 2} in various concentrations were introduced into the zinc-RDX reaction, respectively, which indicate that O{sub 2} made the ignition delay time shorten by over 30%, the effect of H{sub 2}O was not prominent while CO{sub 2} made the ignition delay time lag by around 30%. The results indicate that the Zn-O{sub 2} reaction mainly occurs in O{sub 2}, CO{sub 2} and H{sub 2}O.

Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

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Wolf, G; Schmidt, W

1983-01-01

A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

Protracted chelate therapy after incorporation of plutonium 239 in rats

International Nuclear Information System (INIS)

Gemenetzis, E.

1976-01-01

The author has tested in how far 239 Pu can be mobilized by Ca and Zn, Desfenioxamin B(DFDA) and by combined doses of Ca-DTPA and DFDA. The pre-experiment covered the 239 Pu-metabolism in untreated male and female rats and the distribution in dependence of the way of application. If treatment is started immediately by multiple chelate doses, the first two injections play the main part in the decorporation of 239 Pu. The combination Ca-DTPA30 + DFDA30 μMol x kg -1 is proved to be the best means of decorporation for the whole body. The efficiency of another therapy depends essentially on the treatment used, a daily treatment showing the best effects. If treatment is started later with multiple chelate doses, the total decorporation efficiency is of less value, especially in the skeleton. Aequimolar doses of Ca-DTPA and Zn-DTPA have the same degree of efficiency. This indicates that during protracted chelate treatment starting later, Ca-DTPA could be substituted by the less toxic Zn-DTPA after incorporation of 239 Pu. These results show that intermittant administration of the week's dose is more efficient than a single chelate administration of the whole week's dose at once. Permanent chelate infusion does not seem necessary in any case since it has the same effect as 3 to 5 injections per week and is difficult to carry out in medical practice. Thus, it seems advisable to divide up the weekly dose into 3-5 injections. In case of a wound contamination, the efficiency of immediate intensive treatment depends on the 239 Pu compound used, on the chelate used, and on its dosage. (orig.) [de

Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil

Science.gov (United States)

Fan, Liren; Song, Jiqing; Bai, Wenbo; Wang, Shengping; Zeng, Ming; Li, Xiaoming; Zhou, Yang; Li, Haifeng; Lu, Haiwei

2016-02-01

A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed.

Heavy metal displacement in chelate-irrigated soil during phytoremediation

Science.gov (United States)

Madrid, F.; Liphadzi, M. S.; Kirkham, M. B.

2003-03-01

Heavy metals in wastewater sewage sludge (biosolids), applied to land, contaminate soils. Phytoremediation, the use of plants to clean up toxic heavy metals, might remove them. Chelating agents are added to soil to solubilize the metals for enhanced phytoextraction. Yet no studies follow the displacement and leaching of heavy metals in soil with and without roots following solubilization with chelates. The objective of this work was to determine the mobility of heavy metals in biosolids applied to the surface of soil columns (76 cm long; 17 cm diam.) with or without plants (barley; Hordeum vulgare L.). Three weeks after barley was planted, all columns were irrigated with the disodium salt of the chelating agent, EDTA (ethylenediamine tetraacetic acid) (0.5 g/kg soil). Drainage water, soil, and plants were analyzed for heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, Zn). Total concentrations of the heavy metals in all columns at the end of the experiment generally were lower in the top 30 cm of soil with EDTA than without EDTA. The chelate increased concentrations of heavy metals in shoots. With or without plants, the EDTA mobilized Cd, Fe, Mn, Ni, Pb, and Zn, which leached to drainage water. Drainage water from columns without EDTA had concentrations of these heavy metals below detection limits. Only Cu did not leach in the presence of EDTA. Even though roots retarded the movement of Cd, Fe, Mn, Ni, Pb, and Zn through the EDTA-treated soil from 1 d (Cd) to 5 d (Fe), the drainage water from columns with EDTA had concentrations of Cd, Fe, Mn, and Pb that exceeded drinking water standards by 1.3, 500, 620, and 8.6 times, respectively. Because the chelate rendered Cd, Fe, Mn, Ni, Pb, and Zn mobile, it is suggested that the theory for leaching of soluble salts, put forward by Nielsen and associates in 1965, could be applied to control movement of the heavy metals for maximum uptake during chelate-assisted phytoremediation.

Half-metallic ferromagnetism in Cu-doped zinc-blende ZnO from first principles study

International Nuclear Information System (INIS)

Li, X.F.; Zhang, J.; Xu, B.; Yao, K.L.

2012-01-01

Electronic structures and magnetism of Cu-doped zinc-blende ZnO have been investigated by the first-principle method based on density functional theory (DFT). The results show that Cu can induce stable ferromagnetic ground state. The magnetic moment of supercell including single Cu atom is 1.0 μ B . Electronic structure shows that Cu-doped zinc-blende ZnO is a p-type half-metallic ferromagnet. The half-metal property is mainly attribute to the crystal field splitting of Cu 3d orbital, and the ferromagnetism is dominated by the hole-mediated double exchange mechanism. Therefore, Cu-doped zinc-blende ZnO should be useful in semiconductor spintronics and other applications. - Highlights: → Magnetism of Cu-doped zinc-blende ZnO. → Cu-doped zinc-blende ZnO shows interesting half-metal character. → Total energies calculations reveal that Cu can induce ferromagnetic ground state. → Ferromagnetism dominated by the hole-mediated double exchange mechanism.

Characterization of commercial iron chelates and their behavior in an alkaline and calcareous soil.

Science.gov (United States)

Cantera, Rodrigo G; Zamarreño, Angel M; García-Mina, José M

2002-12-18

Iron deficiency is a common problem for many plants grown in alkaline and calcareous soils. To correct this problem, iron is supplied to plants as chelates. Several iron chelates are sold under diverse trademarks with different characteristics. This work evaluated 18 commercial products containing the most representative chelated iron sources used in agricultural practice in Spain when the study was done, namely the ferric chelates of EDDHA, EDDHMA, EDDCHA, EDDHSA, EDTA, and DTPA. The chelates were comprehensively characterized and quantitated by several techniques, including several chromatographic methods. Iron and chelate dynamics in soil were also studied in a model alkaline and calcareous soil. Results indicate that, in this model soil, among the different iron compounds studied only FeEDDHA and analogues have the capacity to maintain soluble iron in soil solution over time. These results are in agreement with general experience under field conditions. Furthermore, among the different ortho-ortho isomers of FeEDDHA's, FeEDDHSA and FeEDDCHA showed greater capacity than FeEDDHA and FeEDDHMA to maintain the chelated iron in soil solution over time.

Green Synthesized Zinc Oxide (ZnO) Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System.

Science.gov (United States)

Panda, Kamal K; Golari, Dambaru; Venugopal, A; Achary, V Mohan M; Phaomei, Ganngam; Parinandi, Narasimham L; Sahu, Hrushi K; Panda, Brahma B

2017-05-18

Zinc oxide nanoparticles (ZnONP-GS) were synthesised from the precursor zinc acetate (Zn(CH₃COO)₂) through the green route using the milky latex from milk weed ( Calotropis gigantea L. R. Br) by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich) and cationic Zn 2+ from Zn(CH₃COO)₂ were tested in a dose range of 0-100 mg·L -1 for their potency (i) to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O₂ •- , H₂O₂ and • OH), cell death, and lipid peroxidation; (ii) to modulate the activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX); and (iii) to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn 2+ alone.

Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

Science.gov (United States)

Peguero, Julio G; Arenas, Ivan; Lamas, Gervasio A

2014-08-01

Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously. Copyright © 2014 Elsevier Inc. All rights reserved.

The preparation and characterization of novel human-like collagen metal chelates

Energy Technology Data Exchange (ETDEWEB)

Zhu, Chenhui; Sun, Yan [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Wang, Yaoyu [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Xi' an 710069 (China); Luo, Yane, E-mail: luoyane@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering Northwest University, Xi' an 710069 (China); Shaanxi R and D Center of Biomaterials and Fermentation Engineering, Xi' an 710069 (China)

2013-07-01

In order to develop the nutritional trace elements which could be absorbed and utilized effectively, protein chelates were adopted. Calcium, copper and manganese were considered based on their physiological functions, and the new chelates of HLC-Ca, HLC-Cu and HLC-Mn were formed in MOPS or MES buffer and purified by gel chromatography, and then freeze-dried. And they were detected and analyzed by atomic absorption spectrophotometry, ultraviolet–visible absorption (UV–vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, fluorescence quenching method, circular dichroism (CD) and differential scanning calorimetry (DSC). The results showed that some chemical reactions happened between HLC and the three metal ions to form new chemical compounds. The thermodynamic parameters, ∆H, ∆G and ∆S, showed that the chelation process between HLC and metal ions was performed spontaneously. Fluorescence quenching spectra of HLC indicated that the quenching mechanism was static in nature. According to the data of DSC, the new chelates were more stable than the free HLC. And HLC-metal complex was non-toxic to the BHK21 cell through MTT assay. - Highlights: ► HLC-Ca, HLC-Cu and HLC-Mn were new chemical compounds and different to free HLC. ► Possible sites for Ca{sup 2+}, Cu{sup 2+} and Mn{sup 2+} to bind with HLC were presented. ► The chelation process between HLC and metal ions was performed spontaneously. ► The thermodynamic stability of the new chelates was higher than that of free HLC.

Chelate chase of radiopharmaceuticals reversibly bound to monoclonal antibodies improves dosimetry

International Nuclear Information System (INIS)

Goodwin, D.A.; Smith, S.I.; Meares, C.F.; David, G.S.; McTigue, M.; Finston, R.A.

1986-01-01

One hundred micrograms of monoclonal antibody (MoAb) CHA 255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labeled BLEDTA II, GLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-hour tumor and organ distribution in BALB/c mice bearing KHJJ tumors was studied for each compound alone, the antibody complex, and 3 hours following a chelate chase of the antibody complex. Whole-body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-hour whole-body counts dropped 20-60% within 3 hours of administering the chelate chase. Blood concentration fell over 89% within 3 hours of administering the chase and there was a decrease in concentration in all organs, except the kidneys, of 10 to 85%. Theoretical equivalent human doses were calculated from the 24-hour organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads per millicurie. The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labeled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies, greatly improves the radiation dosimetry of tumor imaging agents. 28 references, 5 figures, 5 tables

Controlling lipid oxidation via a biomimetic iron chelating active packaging material.

Science.gov (United States)

Tian, Fang; Decker, Eric A; Goddard, Julie M

2013-12-18

Previously, a siderophore-mimetic metal chelating active packaging film was developed by grafting poly(hydroxamic acid) (PHA) from the surface of polypropylene (PP) films. The objective of the current work was to demonstrate the potential applicability of this PP-g-PHA film to control iron-promoted lipid oxidation in food emulsions. The iron chelating activity of this film was investigated, and the surface chemistry and color intensity of films were also analyzed after iron chelation. In comparison to the iron chelating activity in the free Fe(3+) solution, the PP-g-PHA film retained approximately 50 and 30% of its activity in nitrilotriacetic acid (NTA)/Fe(3+) and citric acid/Fe(3+) solutions, respectively (pH 5.0), indicating a strong chelating strength for iron. The ability of PP-g-PHA films to control lipid oxidation was demonstrated in a model emulsion system (pH 3.0). PP-g-PHA films performed even better than ethylenediaminetetraacetic acid (EDTA) in preventing the formation of volatile oxidation products. The particle size and ζ potential results of emulsions indicated that PP-g-PHA films had no adverse effects on the stability of the emulsion system. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis suggested a non-migratory nature of the PP-g-PHA film surface. These results suggest that such biomimetic, non-migratory metal chelating active packaging films have commercial potential in protecting foods against iron-promoted lipid oxidation.