The Experts below are selected from a list of 3735 Experts worldwide ranked by ideXlab platform
Julia L Brumaghim - One of the best experts on this subject based on the ideXlab platform.
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preventing metal mediated oxidative dna damage with Selenium Compounds
Metallomics, 2011Co-Authors: Erin E Battin, Matthew T Zimmerman, Ria R Ramoutar, Carolyn E Quarles, Julia L BrumaghimAbstract:Copper and iron are two widely studied transition metals associated with hydroxyl radical (˙OH) generation, oxidative damage, and disease development. Because antioxidants ameliorate metal-mediated DNA damage, DNA gel electrophoresis assays were used to quantify the ability of ten Selenium-containing Compounds to inhibit metal-mediated DNA damage by hydroxyl radical. In the CuI/H2O2 system, selenocystine, selenomethionine, and methyl-selenocysteine inhibit DNA damage with IC50 values ranging from 3.34 to 25.1 μM. Four Selenium Compounds also prevent DNA damage from FeII and H2O2. Additional gel electrophoresis experiments indicate that CuI or FeII coordination is responsible for the Selenium antioxidant activity. Mass spectrometry studies show that a 1 : 1 stoichiometry is the most common for iron and copper complexes of the tested Compounds, even if no antioxidant activity is observed, suggesting that metal coordination is necessary but not sufficient for Selenium antioxidant activity. A majority of the Selenium Compounds are electroactive, regardless of antioxidant activity, and the glutathione peroxidase activities of the Selenium Compounds show no correlation to DNA damage inhibition. Thus, metal binding is a primary mechanism of Selenium antioxidant activity, and both the chemical functionality of the Selenium Compound and the metal ion generating damaging hydroxyl radical significantly affect Selenium antioxidant behavior.
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effects of inorganic Selenium Compounds on oxidative dna damage
Journal of Inorganic Biochemistry, 2007Co-Authors: Ria R Ramoutar, Julia L BrumaghimAbstract:Abstract Exposure of Escherichia coli or mammalian cells to H 2 O 2 results in cell death due to iron-mediated DNA damage. Since Selenium Compounds have been examined for their ability to act as antioxidants to neutralize radical species, and inorganic Selenium Compounds are used to supplement protein mixes, infant formula, and animal feed, determining the effect of these Compounds on DNA damage under conditions of oxidative stress is crucial. In the presence of Fe(II) and H 2 O 2 , the effects of Na 2 SeO 4 , Na 2 SeO 3 , SeO 2 (0.5–5000 μM), and Na 2 Se (0.5–200 μM) on DNA damage were quantified using gel electrophoresis. Both Na 2 SeO 4 and Na 2 Se have no effect on DNA damage, whereas SeO 2 inhibits DNA damage and Na 2 SeO 3 shows antioxidant or pro-oxidant activity depending on H 2 O 2 concentration. Similar electrophoresis experiments with [Fe(EDTA)] 2− (400 μM) and Na 2 SeO 3 or SeO 2 show that metal coordination by the Selenium Compound is required for antioxidant activity. In light of these results, Na 2 SeO 4 may be safer than Na 2 SeO 3 for nutritional supplements.
Detlef Balschun - One of the best experts on this subject based on the ideXlab platform.
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Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy
Frontiers in Molecular Neuroscience, 2020Co-Authors: Tariq Ahmed, Ann Van Der Jeugd, Raphaëlle Caillierez, Luc Buée, David Blum, Rudi D’hooge, Detlef BalschunAbstract:A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-β load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic Selenium Compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 μg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism
Ria R Ramoutar - One of the best experts on this subject based on the ideXlab platform.
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preventing metal mediated oxidative dna damage with Selenium Compounds
Metallomics, 2011Co-Authors: Erin E Battin, Matthew T Zimmerman, Ria R Ramoutar, Carolyn E Quarles, Julia L BrumaghimAbstract:Copper and iron are two widely studied transition metals associated with hydroxyl radical (˙OH) generation, oxidative damage, and disease development. Because antioxidants ameliorate metal-mediated DNA damage, DNA gel electrophoresis assays were used to quantify the ability of ten Selenium-containing Compounds to inhibit metal-mediated DNA damage by hydroxyl radical. In the CuI/H2O2 system, selenocystine, selenomethionine, and methyl-selenocysteine inhibit DNA damage with IC50 values ranging from 3.34 to 25.1 μM. Four Selenium Compounds also prevent DNA damage from FeII and H2O2. Additional gel electrophoresis experiments indicate that CuI or FeII coordination is responsible for the Selenium antioxidant activity. Mass spectrometry studies show that a 1 : 1 stoichiometry is the most common for iron and copper complexes of the tested Compounds, even if no antioxidant activity is observed, suggesting that metal coordination is necessary but not sufficient for Selenium antioxidant activity. A majority of the Selenium Compounds are electroactive, regardless of antioxidant activity, and the glutathione peroxidase activities of the Selenium Compounds show no correlation to DNA damage inhibition. Thus, metal binding is a primary mechanism of Selenium antioxidant activity, and both the chemical functionality of the Selenium Compound and the metal ion generating damaging hydroxyl radical significantly affect Selenium antioxidant behavior.
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effects of inorganic Selenium Compounds on oxidative dna damage
Journal of Inorganic Biochemistry, 2007Co-Authors: Ria R Ramoutar, Julia L BrumaghimAbstract:Abstract Exposure of Escherichia coli or mammalian cells to H 2 O 2 results in cell death due to iron-mediated DNA damage. Since Selenium Compounds have been examined for their ability to act as antioxidants to neutralize radical species, and inorganic Selenium Compounds are used to supplement protein mixes, infant formula, and animal feed, determining the effect of these Compounds on DNA damage under conditions of oxidative stress is crucial. In the presence of Fe(II) and H 2 O 2 , the effects of Na 2 SeO 4 , Na 2 SeO 3 , SeO 2 (0.5–5000 μM), and Na 2 Se (0.5–200 μM) on DNA damage were quantified using gel electrophoresis. Both Na 2 SeO 4 and Na 2 Se have no effect on DNA damage, whereas SeO 2 inhibits DNA damage and Na 2 SeO 3 shows antioxidant or pro-oxidant activity depending on H 2 O 2 concentration. Similar electrophoresis experiments with [Fe(EDTA)] 2− (400 μM) and Na 2 SeO 3 or SeO 2 show that metal coordination by the Selenium Compound is required for antioxidant activity. In light of these results, Na 2 SeO 4 may be safer than Na 2 SeO 3 for nutritional supplements.
Tariq Ahmed - One of the best experts on this subject based on the ideXlab platform.
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Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy
Frontiers in Molecular Neuroscience, 2020Co-Authors: Tariq Ahmed, Ann Van Der Jeugd, Raphaëlle Caillierez, Luc Buée, David Blum, Rudi D’hooge, Detlef BalschunAbstract:A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-β load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic Selenium Compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 μg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism
Joao Rocha - One of the best experts on this subject based on the ideXlab platform.
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impact of sin 1 derived peroxynitrite flux on endothelial cell redox homeostasis and bioenergetics protective role of diphenyl diselenide via induction of peroxiredoxins
Free Radical Research, 2015Co-Authors: Bianca Fiuza, Natalia Subelzu, Pablo Calcerrada, Marcos Raniel Straliotto, Lucia Piacenza, Adriana Cassina, Joao Rocha, Rafael Radi, A F De Bem, Gonzalo PeluffoAbstract:AbstractIncreased production of reactive nitrogen (RNS) and oxygen (ROS) species and its detrimental effect to mitochondria are associated with endothelial dysfunction. This study was designed to determine the effect of a peroxynitrite flux, promoted by 1,3-morpholinosydnonimine (SIN-1), in mitochondrial function and some redox homeostasis parameters in bovine aortic endothelial cells (BAEC). Moreover, the effect of diphenyl diselenide (PhSe)2, a simple organic Selenium Compound, in preventing peroxynitrite-mediated cytotoxicity was also investigated. Our results showed that overnight exposure to SIN-1 (250 μM) caused a profound impairment of oxygen consumption, energy generation and reserve capacity in mitochondria of BAEC. Mitochondrial dysfunction resulted in an additional intracellular production of peroxynitrite, amplifying the phenomenon and leading to changes in redox homeostasis. Moreover, we observed an extensive decline in mitochondrial membrane potential (ΔΨm) induced by peroxynitrite and this ...
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comparative studies on dicholesteroyl diselenide and diphenyl diselenide as antioxidant agents and their effect on the activities of na k atpase and δ aminolevulinic acid dehydratase in the rat brain
Neurochemical Research, 2008Co-Authors: Ige Joseph Kade, Antonio L. Braga, Cristina W Nogueira, Marcio W Paixao, Oscar E D Rodrigues, Nilda Vargas Barbosa, Daiana Silva Avila, Joao RochaAbstract:The present study sought to evaluate the effect of a newly synthesized Selenium Compound, dicholesteroyl diselenide (DCDS) and diphenyl diselenide (DPDS) on the activities of delta-aminolevulinate dehydratase and Na+/K+-ATPase in the rat brain. The glutathione peroxidase mimetic activity of the two Compounds as well as their ability to oxidize mono- and di- thiols were also evaluated. The antioxidant effects were tested by measuring the ability of the Compounds to inhibit the formation of thiobarbituric acid reactive species and also their ability to inhibit the formation of protein carbonyls. The results show that DPDS exhibited a higher glutathione peroxidase mimetic activity as well as increased ability to oxidize di-thiols than DCDS. In addition, while DPDS inhibited the formation of thiobarbituric acid reactive species and protein carbonyls, DCDS exhibited a prooxidant effect in all the concentration range (20–167 μM) tested. Also the activities of cerebral delta-aminolevulinate dehydratase and Na+/K+ ATPase were significantly inhibited by DPDS but not by DCDS. In addition, the present results suggested that the inhibition of Na+/K+ ATPase by organodiselenides, possibly involves the modification of the thiol group at the ATP binding site of the enzyme. In conclusion, the results of the present investigation indicated that the non-Selenium moiety of the organochalcogens can have a profound effect on their antioxidant activity and also in their reactivity towards SH groups from low-molecular weight molecules and from brain proteins.
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diphenyl diselenide protects rat hippocampal slices submitted to oxygen glucose deprivation and diminishes inducible nitric oxide synthase immunocontent
Brain Research, 2003Co-Authors: Gabriele Ghisleni, Joao Rocha, Lisiane O Porciuncula, Helena Iturvides Cimarosti, Christianne Gazzana Salbego, Diogo O SouzaAbstract:Abstract Diphenyl diselenide (PhSe)2 is an organic Selenium Compound that has been little studied. In this study we investigated the effects of (PhSe)2 (0.1–3 μM) in a classical model of in vitro brain ischemia, which consists of exposing rat hippocampal slices to oxygen–glucose deprivation (OGD). Hippocampal slices were exposed for 60 min to OGD and the cellular viability (performed by MTT assay) as well as the immunocontent of nitric oxide synthase inducible (iNOS) were evaluated after 180 min of a recovery period. OGD decreased cellular viability by 50% and increased more than twice the immunocontent of iNOS of hippocampal slices. (PhSe)2 (1 and 3 μM) added during OGD and the recovery period abolished both effects. These results demonstrate for the first time the neuroprotective effects of (PhSe)2. Although the Selenium analog—ebselen—has been widely used in ischemia models, our results suggest that other selenoorganic Compounds could be investigated as pharmacological tools against brain disorders.
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effect of organic forms of Selenium on delta aminolevulinate dehydratase from liver kidney and brain of adult rats
Toxicology and Applied Pharmacology, 1998Co-Authors: Nilda Vargas Barbosa, Joao Rocha, G Zeni, Tatiana Emanuelli, Mc M Beque, Antonio L. BragaAbstract:Abstract The inhibitory effect of various forms of organic Selenium Compounds and of diphenyl ditelluride (PhTe) 2 on δ-aminolevulinate dehydratase (δ-ALA-D) from liver, kidney, and brain of rats was investigated because it has been reported that organocalcogens catalyze the oxidation of thiols. Diphenyl diselenide (PhSe) 2 , ρ-chloro-diphenyl diselenide (ρClPhSe) 2 , propyl-2-2-diphenyl diselenide, and propyl-2-methoxy-2-phenyl selenide inhibited δ-ALA-D and the IC50 ranged from 2 to 32 μM depending on the Selenium Compound and whether it was preincubated with the enzyme. (ρClPhSe) 2 was the most potent inhibitor of δ-ALA-D, and preincubation increased the inhibitory potency of all the tested Compounds. Inorganic Selenium Compounds (sodium selenite, Na 2 SeO 3 and Selenium dioxide, SeO 2 ) inhibited δ-ALA-D, and the potency of SeO 2 was greater than that of (ρClPhSe) 2 . Diphenyl ditelluride (PhTe) 2 also inhibited δ-ALA-D but with relatively lower potency than that of organic and inorganic Selenium Compounds. The inhibitory effect of propyl-2-2-diphenyl diselenide and propyl-2-methoxy-2-phenyl selenide seems to be mediated by (PhSe) 2 since the Compounds decomposed rapidly to (PhSe) 2 in aqueous medium. The inhibitory action of Selenium forms on δ-ALA-D from liver, kidney, and brain was antagonized by sulfhydryl protecting agents (dithiotreitol and reduced glutathione). The effects of organic Selenium Compounds on δ-ALA-D were related to the stability of the Se–Se (or Se–C) bond because the Compound methyl-diphenyl diselenide (which possesses the most stable Se–C–Se bond) did not inhibit the enzyme. The inhibitory action of (PhSe) 2 was not related to the formation of oxyradicals in the medium since superoxide dismutase and catalase did not affect the inhibition of δ-ALA-D by (PhSe) 2 . δ-ALA-D from cucumber leaves was not inhibited by Selenium or tellurium Compounds, which suggests that these Compounds act directly on the B or β-site of the animal enzyme. These results suggest that δ-ALA-D from liver, kidney, and brain is a potential molecular target for the toxic effect of organic forms of Selenium and tellurium.