Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis

Amâncio, Olga Maria Silvério; Chaud, Daniela Maria Alves; Yanaguibashi, Gianni; Hilário, Maria Odete Esteves

doi:10.1038/sj.ejcn.1601601

Cited by 40 publications

(18 citation statements)

References 32 publications

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“…Recently, Ala et al [4] reported that plasma copper levels of patients with RA did not change in comparison with healthy controls although zinc levels were decreased. Amancio et al [5] reported that serum copper, but not zinc, was decreased in juvenile RA. Tuncer et al [8] reported a rise in erythrocyte zinc and plasma copper levels and a decrease in erythrocyte copper and plasma zinc levels in patients with RA relative to controls.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, a few studies investigated the possible role of zinc, copper, and selenium in the etiology and pathogenesis of RA [2][3][4][5], but the results are conflicting so further studies are needed on the subject.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, a few studies have investigated the possible role of trace elements in the etiology and pathogenesis of RA [2][3][4][5]. The mechanism(s) by which cells play a role in RA pathogenesis has been the subject of intense research in recent years.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Önal

Nazıroğlu

Çolak

et al. 2010

Biol Trace Elem Res

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The aim of the present study was to measure the changes in serum selenium, zinc, and copper in patients being treated for rheumatoid arthritis. Thirty-two patients and 52 healthy controls were included in the study. The copper level was higher and those of selenium and zinc were lower in the patients relative to controls. Treatment with methotrexate elevated the zinc levels, but not zinc and selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non-steroidal anti-inflammatory drugs did not change the levels of any of the elements studied. The decrease in zinc and selenium levels and elevation in copper levels observed in the patients probably resulted from the defense response of organism and are mediated by inflammatory-like substances.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Önal

Nazıroğlu

Çolak

et al. 2010

Biol Trace Elem Res

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“…12, 2010 An adequate intake of copper during chronic inflammatory diseases, such as rheumatoid arthritis, may influence the efficiency of the organic serum response. 5 Sorenson [6][7][8] attributed the anti-inflammatory activity to the action of the complexes in vivo due to their inherent physico-chemical properties, but Rainsford et al 9 have suggested that the activity may be due to a counter-irritant mechanism triggered by free copper ions. A number of researchers have found that some complexes show similar but not significantly greater anti-inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

Significant anti-inflammatory properties of a copper(II) fenoprofenate complex compared with its parent drug: Physical and chemical characterization of the complex

Agotegaray¹,

Boeris²,

Quinzani³

2010

J. Braz. Chem. Soc.

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A síntese, a caracterização físico-química, as propriedades anti-inflamatórias e a atividade mimética de catecolase do complexo de cobre(II) com a droga anti-inflamatória non-esteroidal Fenoprofeno [ácido 2-(3-fenóxifenil)propiônico] com fórmula [Cu 2 (fen) 2 (dmf) 2 ] (fen = ânion do fenoprofenato, dmf = N,N-dimetilformamida) foram investigadas. Os resultados da análise espectroscópica (espectros de FTIR e EPR) e dados de análise termogravimétrica e térmica diferencial obtidos para o complexo sólido estão de acordo com a sua estrutura dinuclear. Os espectros eletrônicos do produto são igualmente apresentados e discutidos neste trabalho. O complexo foi testado para as suas propriedades anti-inflamatórias em comparação com a droga de referência, o sal de cálcio do Fenoprofeno. A administração oral do composto binuclear inibiu o desenvolvimento do edema induzido por carragenana em ratos; esta inibição foi mais significativa do que a obtida com a droga de referência. O estudo cinético da atividade mimética da catecolase foi realizado espectrofotometricamente, monitorando-se a transformação oxidativa do 3,5-di-terc-butilcatecol na o-quinona correspondente. Os parâmetros cinéticos foram determinados pelo emprego do modelo de Michaelis-Menten, que demonstrou que o novo complexo mimetiza a atividade da catecol oxidase.The synthesis, physicochemical characterization, anti-inflammatory properties and catecholase mimetic activity of the dinuclear complex of copper(II) with the non-steroidal anti-inflammatory drug Fenoprofen [2-(3-phenoxyphenyl)propionic acid] with formula [Cu 2 (fen) 4 (dmf) 2 ] (fen = fenoprofenate anion, dmf = N,N-dimethylformamide) have been investigated. Results of spectroscopic analysis (FTIR and EPR) as well as thermogravimetric and differential thermal analysis data obtained for the solid complex are in good agreement with its dinuclear structure. Electronic spectra of the product are also reported and discussed. The complex was tested for anti-inflammatory properties in comparison to the parent drug, Fenoprofen calcium salt. Oral administration of the dinuclear compound inhibited development of carrageenan-induced oedema in mice; this inhibition was higher than that observed for the parent drug. The kinetic study of the catecholase mimetic activity was carried out spectrophotometrically by monitoring the oxidative transformation of 3,5-di-tert-butylcatechol into the corresponding light-absorbing o-quinone. Kinetic parameters were determined employing the Michaelis-Menten model, showing that the new complex presents catechol oxidase mimetic activity.Keywords: copper(II), Fenoprofen, anti-inflammatory properties, catecholase activity IntroductionThe proposed curative properties of copper(II) carboxylate-based non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous mononuclear and dinuclear copper(II) complexes of NSAIDs with enhanced anti-inflammatory activity.1,2 The elevation of total blood copper levels during acute as well as chronic inflammatory states has been re...

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“…1). Blood levels of copper are increased in several pathological conditions, such as Wilson disease, Indian childhood cirrhosis, juvenile rheumatoid arthritis, thalassemia, and sickle cell anemia (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Copper Inhibits the Water and Glycerol Permeability of Aquaporin-3

Zelenina

Tritto

Bondar

et al. 2004

Journal of Biological Chemistry

123

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Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several other tissues. Erythrocytes are, together with kidney and liver, the main targets for copper toxicity. Here we report that both water and glycerol permeability of human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the natural buffer system in our body, doses in the range of those observed in Wilson disease and in copper poisoning caused significant inhibition. AQP7, another aquaglyceroporin, was insensitive to copper. Copper is an essential trace element in the human body. It is present in the blood and is incorporated in several vital proteins, such as Cu,Zn-SOD, dopamine ␤-hydroxylase, ceruloplasmin, cytochrome c oxidase, etc. (recently reviewed in Ref. 1). Blood levels of copper are increased in several pathological conditions, such as Wilson disease, Indian childhood cirrhosis, juvenile rheumatoid arthritis, thalassemia, and sickle cell anemia (1-5).Aquaporin-3 (AQP3) 1 is an aquaglyceroporin expressed in several mammalian tissues including erythrocytes (6 -12). It is well established that erythrocytes are permeable for glycerol, but the molecular mechanism for this effect is still obscure. It is also well established that glycerol permeability of erythrocytes is extremely sensitive to copper. We have recently shown that AQP3 water permeability is sensitive to nickel (13). Here we report that copper is a potent inhibitor of AQP3 permeability for glycerol and water. We expressed AQP3 in a human cell line and tested the effect of copper on glycerol and water permeability of the transfected cells. Three extracellular amino acid residues were found to be responsible for the copper sensitivity. We modeled the situation when AQP3 is co-expressed with another AQP, not permeable for glycerol, and found that only glycerol but not water permeability will be inhibited by copper in such cells. The results of this study provide a better understanding of processes that occur in severe copper metabolism defects and copper poisoning. MATERIALS AND METHODScDNA Constructs-The constructs for expression of human AQP3 (wild type and mutants) and the long form of AQP4 have been described previously (13). cDNA fragments encoding full-length AQP3 and AQP4 were obtained by amplification from the human lung QUICK-Clone cDNA library (Clontech). cDNA encoding mouse AQP7 was a kind gift from J. M. Carbrey and P. Agre (Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD). The cDNA fragments were subcloned in-frame into the pEGFP-N2 vector for AQP3 tagged with green fluorescent protein (GFP) at the COOH terminus into pIRES2-EGFP vector (Clontech) for AQP3 and GFP expressed in the same cell as separate proteins and into the pEGFP-C2 vector for AQP4 and AQP7 tagged with GFP at NH 2 termini. The point mutations in extracellular loops of human AQP3 were generated by PCR-based mutagenesis using wild-type cDNA as a template and c...

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Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis

Cited by 40 publications

References 32 publications

Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Significant anti-inflammatory properties of a copper(II) fenoprofenate complex compared with its parent drug: Physical and chemical characterization of the complex

Copper Inhibits the Water and Glycerol Permeability of Aquaporin-3

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