102 results on '"Fonseca, Luiz Marcos"'
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2. The reactivity of ortho-methoxy-substituted catechol radicals with sulfhydryl groups: Contribution for the comprehension of the mechanism of inhibition of NADPH oxidase by apocynin
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Kanegae, Marília P.P., da Fonseca, Luiz Marcos, Brunetti, Iguatemy L., de Oliveira Silva, Sueli, and Ximenes, Valdecir F.
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- 2007
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3. Chemiluminescent Determination of Leukocyte Alkaline Phosphatase: An Advantageous Alternative to the Cytochemical Assay
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Kanegae, Marília P.P., Ximenes, Valdecir F., Falcão, Roberto P., Colturato, Virgílio A.R., de Mattos, Éderson R., Brunetti, Iguatemy L., and da Fonseca, Luiz Marcos
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- 2007
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4. Octyl gallate, a food additive with potential beneficial properties to treat Helicobacter pylori infection
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Wolf, Vanessa Gonçalves, primary, Bonacorsi, Cibele, additional, Raddi, Maria Stella Gonçalves, additional, da Fonseca, Luiz Marcos, additional, and Ximenes, Valdecir Farias, additional
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- 2017
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5. Redox-active biflavonoids from Garcinia brasiliensis as inhibitors of neutrophil oxidative burst and human erythrocyte membrane damage
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Saroni Arwa, Phanuel, primary, Zeraik, Maria Luiza, additional, Farias Ximenes, Valdecir, additional, da Fonseca, Luiz Marcos, additional, da Silva Bolzani, Vanderlan, additional, and Siqueira Silva, Dulce Helena, additional
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- 2015
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6. Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors
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Urbaczek, Ana Carolina, primary, Ximenes, Valdecir Farias, additional, Afonso, Ana, additional, Generoso, Wesley Cardoso, additional, Nogueira, Camila Tita, additional, Tansini, Aline, additional, Cappelini, Luciana Teresa Dias, additional, Malagó Júnior, Wilson, additional, Silva, Flávio Henrique da, additional, Fonseca, Luiz Marcos da, additional, and Costa, Paulo Inácio da, additional
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- 2015
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7. Hydrophobicity and antioxidant activity acting together for the beneficial health properties of nordihydroguaiaretic acid
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Paracatu, Luana Chiquetto, primary, Quinello Gomes de Faria, Carolina Maria, additional, Zeraik, Maria Luiza, additional, Quinello, Camila, additional, Rennó, Camila, additional, Palmeira, Patrícia, additional, da Fonseca, Luiz Marcos, additional, and Ximenes, Valdecir Farias, additional
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- 2015
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8. Improvement of Pro-Oxidant Capacity of Protocatechuic Acid by Esterification
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Zeraik, Maria Luiza, primary, Petrônio, Maicon S., additional, Coelho, Dyovani, additional, Regasini, Luis Octavio, additional, Silva, Dulce H. S., additional, da Fonseca, Luiz Marcos, additional, Machado, Sergio A. S., additional, Bolzani, Vanderlan S., additional, and Ximenes, Valdecir F., additional
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- 2014
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9. Lipoperoxidation, loss of cell viability and inhibition of release of IL-8 by human neutrophils in the presence of ketone bodies
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Gileno, M. C. [UNESP], Ximenes, Valdecir Farias [UNESP], Da Fonseca, Luiz Marcos [UNESP], and Universidade Estadual Paulista (Unesp)
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cell culture ,Acetoacetate ,Interleukine-8 ,Lipoperoxidation ,Neutrophils ,incubation temperature ,thiobarbituric acid reactive substance ,neutrophil ,lactate dehydrogenase ,lipid peroxidation ,interleukin 8 ,insulin dependent diabetes mellitus ,ketone body ,zymosan ,enzyme linked immunosorbent assay ,Diabetes mellitus ,3 hydroxybutyric acid ,cytokine release ,fatty acid metabolism ,cytotoxicity ,acidosis ,human ,cell loss ,acetoacetic acid ,cell viability - Abstract
Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:23:58Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:30:24Z : No. of bitstreams: 1 2-s2.0-78649856280.pdf: 363776 bytes, checksum: df7806db29c9aa14a0c6574f6a921c9a (MD5) Made available in DSpace on 2014-05-27T11:23:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-09-01 Portadores de diabetes tipo-1 são acometidos por episódios freqüentes de acidose causada pelo aumento no metabolismo de ácido graxos com conseqüente acúmulo de acetoacetato (AcAc) e β-hidroxibutirato (β -OB). Neste trabalho estudou-se o efeito de concentrações patológicas destes metabólitos na lipoperoxidação, viabilidade e liberação da quimiocina CXCL8 (IL-8) por neutrófilos em cultura. Neutrófilos de indivíduos saudáveis foram isolados por gradiente de densidade (Histopaque 1077/1119) e incubados com os corpos cetônicos. A lipoperoxidação foi determinada pela presença de substâncias reagentes ao ácido tiobarbitúrico (TBARS). A viabilidade celular foi avaliada pela liberação da enzima lactato desidrogenase. A liberação de CXCL8 para o meio extracelular foi medida após cultura de 24 horas de neutrófilos estimulados por zymosan opsonizado por ensaio imunoenzimático (ELISA). O AcAc causou um aumento na lipoperoxidação dos neutrófilos e este efeito foi dependente da sua concentração (p < 0.05; r = 0.99146); não se observou efeito do β-HOB. No estudo do efeito citotóxico, houve aumento dose-dependente da liberação da LDH até 40 mM de AcAc (p < 0.05); não se observou efeito do β-HOB. A liberação de CXCL8 foi suprimida de modo dose dependente por AcAc e β-HOB. Estes resultados sugerem que o acúmulo de corpos cetônicos pode contribuir para aumentar o tempo de remissão de doenças e mesmo estar relacionado com a gravidade destas em indivíduos diabéticos. Type-1 diabetes patients suffer from frequent episodes of acidosis caused by an increased fatty acid metabolism and consequently increased plasma level of acetoacetate (AcAc) and β-hydroxybutyrate (β-HOB). This article describes a study of the effects of pathological concentrations of AcAc and β-HOB on lipoperoxidation, cell viability and the release of the CXCL8 (IL-8) cytokine by activated neutrophils. Neutrophils from healthy donors were isolated by density gradient (Histopaque® 1077/1119) and incubated with the ketone bodies. Lipoperoxidation was determined as thiobarbituric acid reactive substances (TBARS). The cell viability was evaluated by the release of intracellular lactate dehydrogenase. The release of CXCL8 was measured by ELISA in a 24-h culture of opsonized zymosan-stimulated neutrophils. AcAc, but not β-HOB, provoked a dose-dependent increase in the neutrophil membrane lipoperoxidation (p
- Published
- 2009
10. Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure
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Urbaczek, Ana Carolina, primary, Ribeiro, Lívia Carolina de Abreu, additional, Ximenes, Valdecir Farias, additional, Afonso, Ana, additional, Nogueira, Camila Tita, additional, Generoso, Wesley Cardoso, additional, Alberice, Juliana Vieira, additional, Rudnicki, Martina, additional, Ferrer, Renila, additional, Fonseca, Luiz Marcos da, additional, and Costa, Paulo Inácio da, additional
- Published
- 2014
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11. Evaluation of Antimalarial Activity and Toxicity of a New Primaquine Prodrug
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Davanço, Marcelo Gomes, primary, Aguiar, Anna Caroline Campos, additional, dos Santos, Leandro Alves, additional, Padilha, Elias Carvalho, additional, Campos, Michel Leandro, additional, de Andrade, Cleverton Roberto, additional, da Fonseca, Luiz Marcos, additional, dos Santos, Jean Leandro, additional, Chin, Chung Man, additional, Krettli, Antoniana Ursine, additional, and Peccinini, Rosangela Gonçalves, additional
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- 2014
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12. Influence of FcγRIIIb polymorphism on its ability to cooperate with FcγRIIa and CR3 in mediating the oxidative burst of human neutrophils
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Urbaczek, Ana Carolina, primary, Toller-Kawahisa, Juliana Escher, additional, Fonseca, Luiz Marcos, additional, Costa, Paulo Inácio, additional, Faria, Carolina Maria Quinello Gomes, additional, Azzolini, Ana Elisa Caleiro Seixas, additional, Lucisano-Valim, Yara Maria, additional, and Marzocchi-Machado, Cleni Mara, additional
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- 2014
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13. Caffeic Acid Phenethyl Ester: Consequences of Its Hydrophobicity in the Oxidative Functions and Cytokine Release by Leukocytes
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Paracatu, Luana Chiquetto, primary, Faria, Carolina Maria Quinello Gomes, additional, Quinello, Camila, additional, Rennó, Camila, additional, Palmeira, Patricia, additional, Zeraik, Maria Luiza, additional, da Fonseca, Luiz Marcos, additional, and Ximenes, Valdecir Farias, additional
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- 2014
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14. Serum myeloperoxidase level is increased in heavy smokers
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Martins, André B., primary, Ximenes, Valdecir F., additional, and Fonseca, Luiz Marcos da, additional
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- 2013
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15. Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst ofHelicobacter pylori-Stimulated Neutrophil
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Bonacorsi, Cibele, primary, da Fonseca, Luiz Marcos, additional, Raddi, Maria Stella Gonçalves, additional, Kitagawa, Rodrigo Rezende, additional, and Vilegas, Wagner, additional
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- 2013
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16. Anti-Helicobacter pylori activity and oxidative burst inhibition by the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes
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Kitagawa, Rodrigo Rezende, primary, Bonacorsi, Cibele, additional, Fonseca, Luiz Marcos da, additional, Vilegas, Wagner, additional, and Raddi, Maria Stella Gonçalves, additional
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- 2012
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- View/download PDF
17. Effect of Byrsonima crassa and Phenolic Constituents on Helicobacter pylori-Induced Neutrophils Oxidative Burst
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Bonacorsi, Cibele, primary, Raddi, Maria Stella G., additional, da Fonseca, Luiz Marcos, additional, Sannomiya, Miriam, additional, and Vilegas, Wagner, additional
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- 2011
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18. Taurine bromamine: A potent oxidant of tryptophan residues in albumin
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Ximenes, Valdecir F., primary, da Fonseca, Luiz Marcos, additional, and de Almeida, Ana Carolina, additional
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- 2011
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19. Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: Influence of polymer type on phagocytic uptake by polymorphonuclear cells
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Mainardes, Rubiana Mara, primary, Gremião, Maria Palmira Daflon, additional, Brunetti, Iguatemy Lourenço, additional, da Fonseca, Luiz Marcos, additional, and Khalil, Najeh Maissar, additional
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- 2009
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20. A chimeric bispecific antibody improves the cooperation CR/FcgR in mediating the oxidative burst of neutrophils from an individual with FcgRIIa-R131 genotype
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Marzocchi-Machado, Cleni Mara, primary, Urbaczek, Ana Carolina, additional, Fonseca, Luiz Marcos da, additional, Costa, Paulo Inácio da, additional, Azzolini, Ana Elisa Caleiro Seixas, additional, and Lucisano-Valim, Yara Maria, additional
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- 2008
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- View/download PDF
21. Does cotinine act upon reactive oxygen species and peroxidases?
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Vellosa, José Carlos Rebuglio, primary, Maissar Khalil, Najeh, additional, Da Fonseca, Luiz Marcos, additional, Brunetti, Iguatemy Lourenço, additional, and Oliveira, Olga Maria Mascarenhas de Faria, additional
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- 2007
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22. Oxidation of acetylacetone catalyzed by horseradish peroxidase in the absence of hydrogen peroxide
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Rodrigues, Ana Paula, primary, da Fonseca, Luiz Marcos, additional, de Faria Oliveira, Olga M., additional, Brunetti, Iguatemy Lourenço, additional, and Ximenes, Valdecir Farias, additional
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- 2006
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23. Horseradish Peroxidase-Catalyzed Oxidation of Rifampicin: Reaction Rate Enhancement by Co-oxidation with Anti-inflammatory Drugs
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Santos, Fernanda de Jesus Notário dos, primary, Ximenes, Valdecir Farias, additional, Fonseca, Luiz Marcos da, additional, Faria Oliveira, Olga Maria Mascarenhas de, additional, and Brunetti, Iguatemy Lourenço, additional
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- 2005
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24. p-Iodophenol-enhanced luminol chemiluminescent assay applied to discrimination between acute lymphoblastic and minimally differentiated acute myeloid (FAB-M0) or acute megakaryoblastic (FAB-M7) leukemias
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da Costa, Miriane, primary, Ximenes, Valdecir Farias, additional, Brunetti, Iguatemy Lourenço, additional, Falcão, Roberto Passetto, additional, and da Fonseca, Luiz Marcos, additional
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- 2004
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25. Hypochlorous Acid Inhibition by Acetoacetate: Implications on Neutrophil Functions
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Costa, Miriani da, primary, Ximenes, Valdecir Farias, additional, and Fonseca, Luiz Marcos da, additional
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- 2004
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26. Effect of the Isocoumarin Paepalantine on the Luminol and Lucigenin Amplified Chemiluminescence of Rat Neutrophils
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Kitagawa, Rodrigo Rezende, primary, Raddi, Maria Stella Gonçalves, additional, Khalil, Najeh Maissar, additional, Vilegas, Wagner, additional, and Fonseca, Luiz Marcos da, additional
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- 2003
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27. Bioactive Secondary Metabolites from Phomopsis sp., an Endophytic Fungus from Senna spectabilis.
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Chapla, Vanessa Mara, Zeraik, Maria Luiza, Ximenes, Valdecir F., Zanardi, Lisinéia Maria, Lopes, Márcia N., Cavalheiro, Alberto José, Silva, Dulce Helena S., Young, Maria Cláudia M., da Fonseca, Luiz Marcos, Bolzani, Vanderlan S., and Araújo, Angela Regina
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CHEMICAL synthesis ,METABOLITE analysis ,BIOMOLECULES ,CHEMICAL ecology ,BIOLOGICAL products ,ENDOPHYTIC fungi ,PHOMOPSIS diseases - Abstract
Chemical investigation of an acetonitrile fraction from the endophytic fungus Phomopsis sp. led to the isolation of the new natural product 2-hydroxy-alternariol (7) together with the known compounds cytochalasins J (1) and H (2), 5′-epialtenuene (3) and the mycotoxins alternariol monomethyl ether (AME, 4), alternariol (AOH, 5) and cytosporone C (6). The structure of the new compound was elucidated by using 1-D and 2-D NMR (nuclear magnetic resonance) and high resolution mass spectrometry. The cytochalasins J (1) and H (2) and AOH (5) exhibited potent inhibition of the total ROS (reactive oxygen species) produced by stimulated human neutrophils and acted as potent potential anti-inflammatory agents. Moreover, cytochalasin H (2) demonstrated antifungal and acetylcholinesterase enzyme (AChE) inhibition in vitro. [ABSTRACT FROM AUTHOR]
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- 2014
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28. Chemiluminescent determination of esterases in monocytes
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Fonseca, Luiz Marcos da, primary, Yavo, Boni, additional, Catalani, Luiz Henrique, additional, Falcão, Roberto P., additional, Brunetti, Iguatemy Lourenço, additional, and Campa, Ana, additional
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- 1998
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29. Apocynin: Chemical and Biophysical Properties of a NADPH Oxidase Inhibitor.
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Petrônio, Maicon S., Zeraik, Maria Luiza, Da Fonseca, Luiz Marcos, and Ximenes, Valdecir F.
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NADPH oxidase ,NEURODEGENERATION ,CYCLIC voltammetry ,FREE radical scavengers ,FLUORESCENCE quenching ,SERUM albumin ,CIRCULAR dichroism - Abstract
Apocynin is the most employed inhibitor of NADPH oxidase (NOX), a multienzymatic complex capable of catalyzing the one-electron reduction of molecular oxygen to the superoxide anion. Despite controversies about its selectivity, apocynin has been used as one of the most promising drugs in experimental models of inflammatory and neurodegenerative diseases. Here, we aimed to study the chemical and biophysical properties of apocynin. The oxidation potential was determined by cyclic voltammetry (Epa = 0.76V), the hydrophobicity index was calculated (logP = 0.83) and the molar absorption coefficient was determined (ε275nm = 1.1 × 10
4 M-1 cm-1 ). Apocynin was a weak free radical scavenger (as measured using the DPPH, peroxyl radical and nitric oxide assays) when compared to protocatechuic acid, used here as a reference antioxidant. On the other hand, apocynin was more effective than protocatechuic acid as scavenger of the non-radical species hypochlorous acid. Apocynin reacted promptly with the non-radical reactive species H2 O2 only in the presence of peroxidase. This finding is relevant, since it represents a new pathway for depleting H2 O2 in cellular experimental models, besides the direct inhibition of NADPH oxidase. This could be relevant for its application as an inhibitor of NOX4, since this isoform produces H2 O2 and not superoxide anion. The binding parameters calculated by fluorescence quenching showed that apocynin binds to human serum albumin (HSA) with a binding affinity of 2.19 × 104 M-1 . The association did not alter the secondary and tertiary structure of HSA, as verified by synchronous fluorescence and circular dichroism. The displacement of fluorescent probes suggested that apocynin binds to site I and site II of HSA. Considering the current biomedical applications of this phytochemical, the dissemination of these chemical and biophysical properties can be very helpful for scientists and physicians interested in the use of apocynin. [ABSTRACT FROM AUTHOR]- Published
- 2013
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30. Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst of Helicobacter pylori-Stimulated Neutrophil.
- Author
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Bonacorsi, Cibele, da Fonseca, Luiz Marcos, Goncalves Raddi, Maria Stella, Kitagawa, Rodrigo Rezende, and Vilegas, Wagner
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- *
MEDICINAL plants , *ANALYSIS of variance , *ANIMAL experimentation , *BIOLOGICAL models , *GASTRITIS , *HELICOBACTER diseases , *RATS , *RESEARCH funding , *DESCRIPTIVE statistics - Abstract
Ten Brazilian medicinal plants used to treat gastritis and ulcers were carefully selected on the basis of ethnopharmacological importance and antiulcerogenic activity previously described. The antioxidant activity of the methanolic extracts was determined in analysis conditions that simulate a real biological activity on inhibition of the oxidative burst induced in neutrophils using Helicobacter pylori as activator, by a luminol-amplified chemiluminescence assay. The extracts, at low concentration (5μg/mL), exhibited a large variation in inhibitory effects of H. pylori-induced oxidative burst ranging from 48% inhibition to inactive, but all extracts, excluding Byrsonima intermedia, had inhibitory activity over 80% at the concentration of 100 μg/mL. The total suppressive antioxidant capacity measured as the effective concentration, which represents the extract concentration producing 50% inhibition of the chemiluminescence induced by H. pylori, varies from 27.2 to 56.8 μg/mL and was in the following order: Qualea parviflora > Qualea multiflora > Alchornea triplinervia > Qualea grandiflora > Anacardium humile > Davilla elliptica > Mouriri pusa > Byrsonima basiloba > Alchornea glandulosa > Byrsonima intermedia. The main groups of compounds in tested extracts are presented. Differences in the phytochemical profile, quantitatively and qualitatively, of these plants can explain and justify their protective effect on the gastric mucosa caused by the neutrophil-generated ROS that occurs when H. pylori displays its evasion mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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31. Characterization of Myeloid or Lymphoid Acute Leukemia by a Chemiluminescence Assay. Comparison with Immunocytochemistry Using an Antimyeloperoxidase Antibody
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da Fonseca, Luiz Marcos, primary, Brunetti, Iguatemy Lourenço, additional, Rego, Eduardo Magalhães, additional, Garcia, Aglair Bergamo, additional, Cilento, Giuseppe, additional, and Falcão, Roberto Passetto, additional
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- 1993
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32. Effect of Byrsonima crassa and Phenolic Constituents on Helicobacter pylori-Induced Neutrophils Oxidative Burst.
- Author
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Bonacorsi, Cibele, G. Raddi, Maria Stella, da Fonseca, Luiz Marcos, Sannomiya, Miriam, and Vilegas, Wagner
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HELICOBACTER ,PHENOLS ,MALPIGHIACEAE ,NEUTROPHILS ,OXIDATIVE stress ,TRADITIONAL medicine ,ULCER treatment - Abstract
Byrsonima crassa Niedenzu (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+)-catechin > methanol extract > quercetin 3-O-α-Larabinopyranoside > quercetin 3-O-β-D-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC50 value of 3.4 &mgr;g/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms. [ABSTRACT FROM AUTHOR]
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- 2012
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33. Chemiluminescent determination of esterases in monocytes.
- Author
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da Fonseca, Luiz Marcos, Yavo, Boni, Catalani, Luiz Henrique, Falcão, Roberto P., Brunetti, Iguatemy Lourenço, and Campa, Ana
- Published
- 1998
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34. Chemiluminescent determination of esterases in monocytes
- Author
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Fonseca, Luiz Marcos da, Yavo, Boni, Catalani, Luiz Henrique, Falcão, Roberto P., Brunetti, Iguatemy Lourenço, and Campa, Ana
- Abstract
Esterase from monocytes promotes the hydrolysis of 2-methyl-1-propenylbenzoate (MPB) yielding 2-methyl-1-propenol, which is oxidized by horseradish peroxidase/H
2 O2 producing triplet acetone. The chemiluminescence of this reaction can be enhanced by the addition of 9,10-dibromoanthracene-2-sulphonate. The non-specific esterase present in monocytes is responsible for MPB hydrolysis, since (a) the chemiluminescence of the reaction was inhibited by fluoride, and (b) cells that do not contain a significant amount of non-specific esterases, e.g. lymphocytes and neutrophils, did not trigger light emission. The analytical application of this reaction is considered. © 1998 John Wiley & Sons, Ltd.- Published
- 1998
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35. Diapocynin versus apocynin as pretranscriptional inhibitors of NADPH oxidase and cytokine production by peripheral blood mononuclear cells
- Author
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Kanegae, Marília P.P., Condino-Neto, Antonio, Pedroza, Luis Alberto, de Almeida, Ana Carolina, Rehder, Jussara, da Fonseca, Luiz Marcos, and Ximenes, Valdecir F.
- Subjects
- *
GENETIC transcription , *ENZYME inhibitors , *CYTOKINES , *NAD (Coenzyme) , *BLOOD cells , *CELL nuclei , *PHAGOCYTOSIS , *GENE expression , *MESSENGER RNA - Abstract
Abstract: Apocynin has been extensively used as an inhibitor of NADPH oxidase (NOX) in many experimental models using phagocytic and non-phagocytic cells. Currently, there is some controversy about the efficacy of apocynin in non-phagocytic cells, but in phagocytes the reported results are consistent, which could be due to the presence of myeloperoxidase in these cells. This enzyme has been proposed as responsible for activating apocynin by generating its dimer, diapocynin, which is supposed to be the active compound that prevents NADPH oxidase complex assembly and activation. Here, we synthesized diapocynin and studied its effect on inhibition of gp91 phox RNA expression. We found that diapocynin strongly inhibited the expression of gp91 phox mRNA in peripheral blood mononuclear cells (PBMC). Only at a higher concentration, apocynin was able to exert the same effect. We also compared the apocynin and diapocynin efficacy as inhibitors of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) production in response to lipopolysaccharide (LPS)-activated PBMC. Although apocynin did inhibit TNF-α production, diapocynin had a much more pronounced effect, on both TNF-α and IL-10 production. In conclusion, these findings suggest that the bioconversion of apocynin to diapocynin is an important issue not limited to enzymatic activity inhibition, but also for other biological effects as gp91 phox mRNA expression and cytokine production. Hence, as diapocynin can be easily prepared from apocynin, a one-step synthesis, we recommend its use in studies where the biological effects of apocynin are searched. [Copyright &y& Elsevier]
- Published
- 2010
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36. Effect of subinhibitory concentration of chlorhexidine on Streptococcus agalactiae virulence factor expression
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Galice, Denize Maria, Bonacorsi, Cibele, Soares, Verônica Cristina Gomes, Raddi, Maria Stella Gonçalves, and Fonseca, Luiz Marcos da
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STREPTOCOCCUS , *DISINFECTION & disinfectants , *CHLORHEXIDINE , *IMMUNOLOGY - Abstract
Abstract: The aim of the present study was to investigate the effect of chlorhexidine at subinhibitory concentration (50% minimal inhibitory concentration (MIC)) on the growth, cytolysin expression and phagocytosis of Streptococcus agalactiae ATCC 13813. Bacterial growth with and without chlorhexidine treatment was monitored by turbidity measurements, and exocytolysins were estimated by neutral red uptake assay by the McCoy cell line. The phagocytic process was evaluated using luminol-enhanced chemiluminescence to follow the respiratory burst of polymorphonuclear neutrophils exposed to bacteria. Chlorhexidine-treated culture did not exhibit a detectable decrease in cell growth, and no statistically significant reduction in the respiratory burst of polymorphonuclear neutrophils was observed. However, growth in the presence of chlorhexidine resulted in a significant reduction of S. agalactiae exocytolysins. Although 50% MIC of chlorhexidine did not interfere with S. agalactiae growth and phagocytosis, the knowledge that this concentration was still able to alter some bacterial virulence parameters may be useful in its therapeutic applications. [Copyright &y& Elsevier]
- Published
- 2006
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37. Gallic acid and its esters as anti - Helicobacter pylori agents and scavenger of oxidants produced by neutrophils
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Wolf, Vanessa Gonçalves [UNESP], Universidade Estadual Paulista (Unesp), Ximenes, Valdecir Farias [UNESP], and Fonseca, Luiz Marcos da [UNESP]
- Subjects
Alquil galatos ,Helicobacter pylori ,NADPH oxidase ,Ácido gálico ,Gallic acid ,Neutrófilo ,Neutrophil ,Alkyl gallates ,Oxidative burst ,Burst oxidativo - Abstract
Submitted by VANESSA GONÇALVES WOLF null (nessa.wolf@hotmail.com) on 2017-07-13T23:39:50Z No. of bitstreams: 1 20170708145234dissertacao_final_vanessa_goncalves_wolf_corrigida_jul_8.pdf: 3123091 bytes, checksum: 0e5f498e0767893a065858a9ae558c1c (MD5) Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-07-14T18:44:45Z (GMT) No. of bitstreams: 1 wolf_vg_me_arafcf.pdf: 3123091 bytes, checksum: 0e5f498e0767893a065858a9ae558c1c (MD5) Made available in DSpace on 2017-07-14T18:44:45Z (GMT). No. of bitstreams: 1 wolf_vg_me_arafcf.pdf: 3123091 bytes, checksum: 0e5f498e0767893a065858a9ae558c1c (MD5) Previous issue date: 2017-06-22 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Helicobacter pylori é um dos principais causadores de gastrite crônica e úlcera péptica, e embora o mecanismo envolvido na inflamação gástrica por esta bactéria não esteja completamente elucidado, sabe-se do importante papel das espécies reativas de oxigênio (EROs) produzidas por polimorfonucleares neutrófilos, que são atraídos e ativados pelo agente da infecção, sem que, entretanto, consigam debelar a mesma, mas que contribuem fortemente para a lesão tecidual e o processo inflamatório crônico. Diante disso, tem aumentado a busca de novas estratégias de tratamento que possam levar à redução do estresse oxidativo gerado no sítio da infecção, com consequente redução do processo inflamatório. Neste sentido, ácido gálico, juntamente com seus ésteres (galato de metila, propila, hexila e octila), foram utilizados neste estudo, com o objetivo de avaliar suas ações como inibidores da liberação de EROs por neutrófilos ativados, bem como seus efeitos antimicrobianos sobre H. pylori. Para a avaliação da atividade antioxidante dessas substâncias foram realizados ensaios livres de células (efeito supressor sobre o radical DPPH e sobre radicais peroxila), e o efeito anti-EROs foi avaliado utilizando neutrófilos isolados de sangue humano estimulados por H. pylori, Zymosan ou PMA, através de ensaio quimiluminescente dependente de luminol ou lucigenina, ensaio com WST-1, ensaio de inibição da produção de HOCl, e o teste do NBT. Ensaio antimicrobiano foi realizado através da técnica de microdiluição em caldo. A presença da cadeia lateral carbônica levou a um significativo aumento na capacidade dos ésteres em inibir a produção de EROs por neutrófilos ativados, quando comparados ao ácido precursor, com destaque para os galatos de hexila e octila, que inibiram em quase 100% a produção de radical ânion superóxido, bem como de todas as EROs do burst oxidativo de forma geral. Galatos de octila e hexila também mostraram-se ser as moléculas com maior atividade antimicrobiana sobre H. pylori, com um valor de CIM de 125 e 250g/mL, respectivamente, ao passo que as demais substâncias apresentaram valor de CIM acima de 1000 g/mL. Os resultados obtidos mostram o grande potencial dos ésteres do ácido gálico quanto à suas atividades anti-H. pylori e anti-EROs, e além disso demonstram a importância da presença de uma cadeia carbônica lateral, conferindo maior hidrofobicidade à molécula, para obter-se a máxima atividade antimicrobiana in vitro e a máxima atividade antioxidante em modelo ex vivo. Assim, os ésteres do ácido gálico apresentam-se como moléculas promissoras no tratamento da infecção por Helicobacter pylori, apresentando ação antimicrobiana sobre o mesmo, bem como na redução do estresse oxidativo gerado no sítio da infecção. Helicobacter pylori is one of major cause of chronic gastritis and peptic ulcer disease, and although the mechanism involved in gastric inflammation by this bacterium is not fully understood, it is know the important role of reactive oxygen species (ROS) produced by polymorphonuclear neutrophils (PMNs), which are attracted and activated by infection agent, without, however, to be able to overcome the same, but which contribute strongly to the tissue damage and chronic inflammation. Therefore, it has increased the search for new strategies of treatment that can lead to the reduction of the oxidative stress generated at the infection site, with consequent reduction of the inflammatory process. In this sense, gallic acid, together with its esters (methyl, propyl, hexyl and octyl gallate), were used in this study, with the aim of evaluating their actions as inhibitors of ROS release by activated neutrophils, as well as their antimicrobial effects on H. pylori. Cell-free assays (suppressor effect on the DPPH radical and peroxyl radicals) were performed to evaluate the antioxidant activity of these substances, and the anti-EROs effect was evaluated using neutrophils isolated from human blood, stimulated by H. pylori, Zymosan or PMA, through luminol-dependent or lucigenin-dependent chemiluminescent assay, WST-1 assay, inhibition of HOCl production assay, and the NBT assay. Antimicrobial assay was performed by broth microdilution technique. The presence of the carbonic side chain led to a significant increase in the ability of the esters to inhibit the ROS production by activated neutrophils when compared to the precursor acid, especially hexyl and octyl gallates, which inhibited practically 100% of the superoxide anion radical production, as well as all ROS of the oxidative burst in general. Octyl and hexyl gallates were also shown to be the molecules with the highest antimicrobial activity on H. pylori, with a MIC value of 125 and 250 μg/mL, respectively, while the other substances had a MIC value higher than 1000 g/ml. The results show the great potential of the esters of gallic acid for their anti-H. pylori and anti-EROs activities, and furthermore demonstrate the importance of the presence of a lateral carbonic chain, giving greater hydrophobicity to the molecule, to obtain the maximum antimicrobial activity in vitro and the maximum antioxidant activity in an ex vivo model. Thus, esters of gallic acid are promising molecules in the treatment of Helicobacter pylori infection, presenting antimicrobial action on the same, as well as reducing the oxidative stress generated at the site of infection. CNPq: 130667/2015-3 FAPESP: 2015/21693-0
- Published
- 2017
38. Study of Relationship Between Chemical Structure and Biological Activity of NADPH Oxidase Inhibitors in Leukocyte: relevance of Oxidisability and hydrophobicity
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Paracatu, Luana Chiquetto [UNESP], Universidade Estadual Paulista (Unesp), Ximenes, Valdecir Farias [UNESP], and Fonseca, Luiz Marcos da [UNESP]
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Éster Fenetílico do ácido cafeico ,Leucócitos ,Ânion superóxido ,Caffeic acid phenethyl ester ,NADPH Oxidase ,Leucocytes ,Superoxide anion - Abstract
Submitted by LUANA CHIQUETTO PARACATÚ null (luanachiquetto@hotmail.com) on 2016-07-14T18:15:23Z No. of bitstreams: 1 TESE - Luana Chiquetto.pdf: 2823701 bytes, checksum: 584996ba0cd6c6754d03400de9c6de73 (MD5) Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-07-18T20:01:01Z (GMT) No. of bitstreams: 1 paracatu_lc_dr_arafcf.pdf: 2823701 bytes, checksum: 584996ba0cd6c6754d03400de9c6de73 (MD5) Made available in DSpace on 2016-07-18T20:01:01Z (GMT). No. of bitstreams: 1 paracatu_lc_dr_arafcf.pdf: 2823701 bytes, checksum: 584996ba0cd6c6754d03400de9c6de73 (MD5) Previous issue date: 2016-06-17 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Inúmeras patologias têm a sua gênese e/ou progressão relacionadas à produção desregulada de intermediários oxidantes. O complexo multienzimático NADPH oxidase é um dos componentes de maior relevância neste contexto, pois é uma das principais fontes de ânion superóxido no organismo animal. Sendo expresso em inúmeros tecidos, incluindo leucócitos e células do tecido endotelial, o desenvolvimento de inibidores eficientes deste complexo enzimático poderá significar uma nova terapêutica para o tratamento de doenças inflamatórias crônicas. Com objetivo de explorar a relação entre a estrutura molecular, as propriedades químicas e atividades biológicas, utilizamos o éster fenetílico do ácido cafeico (CAPE) como inibidor do complexo enzimático NADPH oxidase e comparamos sua eficácia com o seu precursor ácido cafeico e os derivados, éster fenetílico do ácido cinâmico e o ácido clorogênico, correlacionando-os a respeito a sua hidrofobicidade, propriedades redox e inibição do complexo NADPH oxidase em leucócitos ativados. A hipótese seria de que um aumento da hidrofobicidade provocado pela esterificação do ácido cafeico poderia facilitar o seu acesso à membrana celular e assim alterar seu efeito como possível inibidor de NADPH Oxidase. Os resultados, em ensaios in vitro, mostraram que as alterações na hidrofobicidade não provocaram alterações significativas no potencial de oxidação e potencial antioxidantes dos compostos testados. Quando testados em leucócitos ativados (modelos ex vivo), a esterificação provocou uma melhora significativa na capacidade de inibição do complexo NADPH oxidase. Este potente efeito se propagou às EROs decorrentes de ânion superóxido e produzidas por leucócitos, como peróxido de hidrogênio e ácido hipocloroso, entretanto, sem alterar a capacidade fagocítica dos leucócitos. Os resultados deste estudo mostram que nos ensaios celulares o CAPE foi o composto mais potente em relação ao seu precursor ácido e ácido clorogênico, sendo significativamente mais efetivo na inibição da produção das EROs. Da mesma forma, CAPE foi o inibidor mais eficaz da expressão de TNF-α e IL-10 por Staphylococcus aureus células estimuladas. Em conclusão, a presença do grupo catecol e a maior hidrofobicidade, do CAPE, foram essenciais para os efeitos biológicos, confirmando nossa hipótese. Considerando-se o envolvimento da NADPH-oxidases na génese e progressão de doenças inflamatórias, CAPE deve ser considerada como uma droga anti-inflamatória promissora. Several diseases have their genesis and / or progression related to unregulated production of oxidants intermediates. The multienzymatic complex NADPH oxidase is one of the most important components in this context because it is a major source of superoxide anion in animal organisms. It is expressed in numerous tissues, including leukocytes and endothelial tissue cells. Developing effective inhibitors of this enzyme complex may indicate a new therapy for the treatment of chronic inflammatory diseases. Several studies have described numerous anti-inflammatory properties attributed to caffeic acid phenethyl ester (CAPE), an active component found in propolis. In order to explore the relationship between the molecular structure, chemical properties and biological activities, we used CAPE to inhibit the enzyme complex NADPH oxidase and compare its efficacy with the its precursor caffeic acid and derivatives, phenethyl ester of cinnamic acid and chlorogenic acid, correlating them with regard to hydrophobicity, redox properties and inhibition of NADPH oxidase complex on activated leukocytes. The hypothesis was that an increase of hydrophobicity caused by the esterification of caffeic acid could facilitate access to cell membranes and thereby alter its effect as a possible inhibitor of NADPH oxidase. The results (in vitro), showed that the changes in hydrophobicity did not provoke significant changes in the oxidation potential and antiradical potency of the tested compounds. But when tested in activated leukocytes (ex vivo), the esterification caused a significant improvement in the ability to inhibit the NADPH oxidase complex. This potent inhibition effect resulted also in the blockage of production of hypochlorous acid, however, without altering the phagocytic ability of leukocytes. The results of this study show that in cellular assays, CAPE was the most potent compound in comparison to caffeic acid and chlorogenic acid, significantly more effective in inhibiting the production of ROS. Likewise, CAPE was the most effective inhibitor of expression of TNF-α and IL-10 in Staphylococcus aureus stimulated cells. In conclusion, the presence of the catechol moiety and the higher hydrophobicity of CAPE were essential for the biological effects. Considering the involvement of NADPH oxidases in the genesis and progression of inflammatory diseases, CAPE should be considered as a promising anti-inflammatory drug.
- Published
- 2016
39. Ácido protocatecúico e seus ésteres alquílicos: propriedades antioxidantes e seus efeitos no metabolismo oxidativo de leucócitos
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Faria, Carolina Maria Quinello Gomes de [UNESP], Universidade Estadual Paulista (Unesp), Ximenes, Valdecir Farias [UNESP], and Fonseca, Luiz Marcos da [UNESP]
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Bioquímica ,Ácido fenólico ,Leucócitos ,Membranas celulares ,NADPH Oxidase ,Membranas (Biologia) - Abstract
Made available in DSpace on 2015-01-26T13:21:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-07Bitstream added on 2015-01-26T13:30:22Z : No. of bitstreams: 1 000797249_20150903.pdf: 551884 bytes, checksum: 6f249a087df5eb16de47f2472dd301e1 (MD5) Bitstreams deleted on 2015-09-03T13:12:49Z: 000797249_20150903.pdf,. Added 1 bitstream(s) on 2015-09-03T13:13:21Z : No. of bitstreams: 1 000797249.pdf: 3130829 bytes, checksum: b6ad1f9fa1251f1ff059a82f758f9992 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Nicotinamida adenina dinucleotídeo fosfato (NADPH) oxidases são complexos multienzimáticos associados à membrana celular cuja principal função é catalisar a redução de oxigênio molecular a ânion superóxido (O2 •-). Em leucócitos, este é o mecanismo primário pelo qual estas células produzem espécies reativas de oxigênio (EROs), as quais estão envolvidas tanto nos mecanismos de defesa imune inato, quanto em processos oxidativos deletérios característicos de muitas patologias de cunho crônico inflamatório. Neste trabalho apresentamos os resultados obtidos e proposta de mecanismo de inibição do complexo NADPH oxidase por um conjunto de ésteres alquílicos sintéticos derivados do ácido protocatecúico, sendo este último um ácido fenólico presente em diversas plantas e com destacada capacidade antiradicalar. Nossa hipótese foi de que o aumento da hidrofobicidade provocado pela esterificação do ácido protocatecúico poderia facilitar o seu acesso à membrana celular e assim alterar seus efeitos biológicos. Esta hipótese se confirmou, pois muito mais do que melhorar a sua capacidade anti-radicalar (modelos in vitro), a esterificação provocou uma melhora significativa na capacidade de inibição do complexo NADPH oxidase em leucócitos (modelos ex vivo). Este efeito se propagou às EROs decorrentes de ânion superóxido e produzidas por leucócitos como peróxido de hidrogênio e ácido hipocloroso, sem entretanto alterar a sua capacidade fagocítica. Cabe frisar que não se trata de ação supressora sobre estas EROs, mas sim efetiva inibição de sua formação, o que foi demonstrado pelos diversos controles empregados. A esterificação do ácido protocatecúico também causou efetiva melhora na capacidade deste como inibidor das citocinas TNF-a e IL-10 produzidas por leucócitos mononucleares de sangue periférico. Considerando a baixa toxicidade e baixo custo de síntese desses ésteres, propomos que os mesmos ... Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multienzymatic complexes associated to the cell membranes whose main function is to catalyze the reduction of molecular oxygen to superoxide (O2 •-). In leukocytes, this is the primary mechanism through which these cells produce reactive oxygen species (ROS), which are involved in both the innate immune defense mechanisms and deleterious oxidative processes, which characterizes many chronic inflammatory diseases. In this thesis we present the results and proposed mechanism of inhibition of the NADPH oxidase complex by a group of synthetic alkyl esters derived from protocatechuic acid, a phenolic acid present in many plants with detached antiradical capacity. Our hypothesis was that the increase in hydrophobicity caused by esterification of protocatechuic acid could facilitate their access to the cell membrane and thereby alter their biological effects. This hypothesis was confirmed, since not only its anti-radical activity was increased (in vitro models), but also caused a significant improvement in their ability to inhibit NADPH oxidase complex in leukocytes (ex vivo models). This effect has spread to ROS derived from superoxide anion and produced by leukocytes such as hydrogen peroxide and hypochlorous acid, without altering their phagocytic capacity. It must be emphasize that the observed cellular effects were not due to simple suppressive action on ROS, but effective inhibition of its formation, which was demonstrated by the various control experiments. The esterification of protocatechuic acid also caused improvement in their capacity as inhibitor of TNF-a and IL-10 production by peripheral blood mononuclear leukocytes. Considering the low toxicity and low cost of synthesis of these esters, we suggest that they could be used in in vivo models as promising anti-inflammatory ...
- Published
- 2014
40. Avaliação in vitro e ex vivo da atividade anti-espécies reativas de oxigênio (EROs) do ácido ferúlico e seus ésteres e seu perfil de liberação em preparações dermatológicas
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Nazaré, Ana Carolina [UNESP], Universidade Estadual Paulista (Unesp), Fonseca, Luiz Marcos da [UNESP], and Ximenes, Valdecir Farias [UNESP]
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Agentes dermatológicos ,Ácido fenólico ,Antioxidantes ,Reações quimicas ,Antioxidants - Abstract
Made available in DSpace on 2014-06-11T19:29:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-10-25Bitstream added on 2014-06-13T19:38:13Z : No. of bitstreams: 1 nazare_ac_me_arafcf_parcial.pdf: 190582 bytes, checksum: b284a45994fcad0ef3487af946b3201f (MD5) Bitstreams deleted on 2014-12-01T14:49:45Z: nazare_ac_me_arafcf_parcial.pdf,Bitstream added on 2014-12-01T14:50:23Z : No. of bitstreams: 1 000726315.pdf: 1055101 bytes, checksum: 8b303973d6209265b52eb563aa23e222 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Os processos oxidativos podem ser evitados pela utilização de substâncias antioxidantes que possuem propriedades de impedir ou diminuir o desencadeamento das reações oxidativas. Antioxidantes fenólicos podem funcionar como sequestradores de radicais e algumas vezes como quelantes de metais. Alguns produtos intermediários, formados pela ação destes antioxidantes, são relativamente estáveis devido à estabilização por ressonância do anel aromático presente nestas substâncias. Devido à relação entre a geração endógena de espécies reativas de oxigênio (EROs) e a gênese ou a progressão de inúmeras patologias de cunho inflamatório e degenerativo, as aplicações experimentais e clínicas de substâncias com propriedades antioxidantes aumentam a cada dia. O mesmo pode ser dito para as aplicações de uso tópico, onde antioxidantes podem conferir proteção contra EROs e ainda promover a estabilização química das emulsões. No presente trabalho foram estudadas as características químicas e biológicas do ácido ferúlico e ferulatos de alquila, os quais foram sintetizados no Instituto de Química – UNESP – Araraquara/SP. Especificamente foi avaliado a lipofilicidade dos mesmos a fim de visualizar possíveis alterações no potencial antioxidante destas substâncias. Estas alterações puderam ser observadas quando comparamos os resultados dos ensaios químicos com os ensaios biológicos, onde o potencial antioxidante se inverteu. Nos ensaios químicos em meio aquoso, como por exemplo, o DPPH, o ácido ferúlico (CI50 23,54) apresentou maior potencial antioxidante frente aos ferulatos de alquila (CI50 > 23,54), já nos ensaios celulares, usando como exemplo o ensaio de lucigenina, os ferulatos (com exceção o F7) apresentaram maior potencial antioxidante frente ao ácido ferúlico F2 > F1 > F4 > F7 > F0, isso pode estar relacionado à cadeia alquílica... Oxidative processes can be avoided by the use of antioxidants to prevent or lessen property triggering of oxidative reactions. Phenolic antioxidants may act as radical scavengers and sometimes as metal chelators. Some intermediate products formed by the action of these antioxidants are relatively stable due to resonance stabilization of the aromatic ring present in these substances. Because of the relationship between the endogenous generation of reactive oxygen species (ROS) and the genesis or progression of numerous diseases imprint inflammatory and degenerative experimental and clinical applications of substances with antioxidant properties increase every day. The same can be said for topical applications, where antioxidants may confer protection against ROS and further promote the chemical stabilization of emulsions. In the present study, the chemical and biological characteristics of ferulic acid and alkyl ferulates, which were synthesized at the Institute of Chemistry - UNESP - Araraquara / SP. Specifically was evaluated lipophilicity to visualize possible changes in antioxidant potential of these substances. These changes could be observed when comparing the chemical assays with biological assays, where the antioxidant potential was reversed. In the test chemical in aqueous medium, for example DPPH ferulic acid (IC50 23,54) has a higher antioxidant activity against alkyl ferulates (IC50 > 23.54) already in cellular assays using the assay as an example of lucigenin the ferulates (except F7) showed higher antioxidant ferulic acid against F2 > F1 > F4 > F7 > F0, this may be related to the alkyl ferulates chain of representing low solubility in aqueous media. And in cellular assays, ferulates have the ability to interact with the alkyl chain with the plasma membrane of cells. In our last step different formulations were... (Complete abstract click electronic access below)
- Published
- 2013
41. Interação da proteina e2 do vírus da hepatite c com o receptor de ldl e cd81 presentes em células endoteliais e ativação da resposta inflamatória
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Urbaczek, Ana Carolina [UNESP], Universidade Estadual Paulista (Unesp), and Fonseca, Luiz Marcos da [UNESP]
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Fígado - Cirrose ,Hepatite C ,Fígado - Câncer ,Proteina de ligação ,Hepatitis C - Abstract
Made available in DSpace on 2014-12-02T11:16:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-11-30Bitstream added on 2014-12-02T11:21:11Z : No. of bitstreams: 1 000792799_20141231.pdf: 121704 bytes, checksum: 8ea6280bc854bb7701833438b6a4bcf7 (MD5) Bitstreams deleted on 2015-01-05T11:00:54Z: 000792799_20141231.pdf,Bitstream added on 2015-01-05T11:01:50Z : No. of bitstreams: 1 000792799.pdf: 4115128 bytes, checksum: bf08d34c13536fc5692eaddb40e4fe2c (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Aproximadamente 170 milhões de pessoas no mundo estão cronicamente infectadas pelo vírus da Hepatite C (HCV). No Brasil, os números já chegam a 3 milhões. A persistência da infecção pelo HCV no fígado leva à cronificação da doença, cirrose e hepatocarcinoma. A proteína de envelope 2 (E2) do HCV é a responsável pelo seu acoplamento à célula hospedeira através da interação com receptores de superfície celular, como o R-LDL e o CD81, entre outros. Como as alterações na micro e macrovasculatura hepática, têm sido apontadas como elementos fundamentais na histogênese e prognóstico da doença, o objetivo deste estudo foi avaliar a interação da proteína E2 recombinante com os R-LDL presentes na superfície de células endoteliais (ECV304 e HUVEC) sob influência de LDL e da glicosilação protéica. Também avaliar a resposta inflamatória das células endoteliais à interação com estas proteínas. A proteína E2 foi expressa em dois sistemas heterólogos, E. coli e P. pastoris, para avaliação da glicosilação e da interação com LDL na ligação aos R-LDL das células através de citometria de fluxo. As proteínas também foram avaliadas em testes biológicos quanto à indução celular de produção de espécies reativas de oxigênio (EROs totais – QL e H2O2 - citometria de fluxo), NO (QL em fase gasosa e por método de Griess), arginase (espectrofotometria), IL-8 (ELISA), VEGF (ELISA) e morte celular (MTT - espectrofotometria e por anexina V e PI - citometria de fluxo). Os resultados obtidos revelaram que as proteínas E2 recombinantes podem interagir com os R-LDL das células endoteliais após a ligação ao LDL e que esta ligação pode ser melhorada pela glicosilação (E2L) (p
- Published
- 2012
42. Ácido cafeico e seus ésteres: inibição do burst oxidativo de neutrófilos e efeito anti-Helicobacter pylori
- Author
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Paracatu, Luana Chiquetto [UNESP], Universidade Estadual Paulista (Unesp), and Fonseca, Luiz Marcos da [UNESP]
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Ácido fenólico ,Phenolic acids ,Esteres ,Antioxidantes ,Esters ,Antioxidants - Abstract
Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-29Bitstream added on 2014-06-13T19:25:33Z : No. of bitstreams: 1 paracatu_lc_me_arafcf.pdf: 657634 bytes, checksum: 11ed69514067f35e0f7dba9e2f7ec13c (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Estadual Paulista (UNESP) A ação patogênica do Helicobacter pylori envolve a colonização do trato gastrointestinal e a produção de EROs por neutrófilos atraídos e ativados pelo agente da infecção. A reação mediada pelos PMN é, todavia, ineficaz para eliminar o H. pylori e as EROs contribuem para a lesão tecidual e desenvolvimento de gastrites e úlcera péptica. O ácido cafeico é um dos mais importantes compostos fenólicos, e apresenta diferentes propriedades biológicas, entre elas antioxidante e antimicrobiana. O objetivo deste estudo foi avaliar a atividade antioxidante e anti-H.pylori do ácido cafeico e seus ésteres. Foram avaliados os ésteres: cafelato de metila, cafelato de butila e cafelato de heptila e realizada uma comparação entre as propriedades antioxidantes do ácido cafeico e tais ésteres, por meio de ensaio de quimiluminescência dependente de luminol e lucigenina, ensaio de inibição da produção do ácido hipocloroso e também ensaios morfológicos com e sem a presença de NBT. Os resultados deste estudo mostraram que os ésteres do ácido cafeico apresentaram melhores resultados em comparação com o ácido cafeico para a capacidade antioxidante. O cafelato de heptila apresentou os melhores resultados para a quimiluminescência dependente de luminol e lucigenina induzida por H. pylori e/ou zymozan opsonizado na concentração de 10 µM e 1 µM . O efeito do ácido cafeico e seus ésteres, também foi estudado na inibição da produção de ácido hipocloroso por neutrófilos ativados com PMA. O cafelato de heptila novamente provou ser melhor em capacidade antioxidante, levando a crer que a lipofilicidade deste composto... The pathogenic action of Helicobacter pylori involves the colonization of the gastrointestinal tract and ROS production by neutrophils attracted and activated by the agent of infection. However, the reaction mediated PMN is ineffective to remove the H. pylori and ROS contribute to tissue damage and development of gastritis and peptic ulcer. Caffeic acid is one of most important phenolic compounds, and has different biological properties including antioxidant and antimicrobial activities. The aim of this study was to evaluate the antioxidant and anti-Helicobacter pylori activity of caffeic acid and esters. Esters evaluated: methyl caffeic acid ester, butyl caffeic acid ester and heptyl caffeic acid ester and a comparison between the antioxidant properties of caffeic acid and these esters through luminol and lucigenin chemiluminescence assay dependent, inhibition of production of hypochlorous acid assay, morphological tests with and without the presence of NBT. The results of this study showed that the esters of caffeic acid had better results in comparison with caffeic acid to their antioxidant capacity. The heptyl caffeic acid ester showed the best results for the luminol and lucigenin dependent chemiluminescence induced by H. pylori and / or opsonized zymozan in the concentrations of 10 µM and 1 µM. The effect of caffeic acid and esters, was also studied in inhibiting of production of hypochlorous acid by neutrophils activated with PMA. The heptyl caffeic acid ester again proved to be better at antioxidant activity, implying that... (Complete abstract click electronic access below)
- Published
- 2012
43. Concentração e atividade sérica da mieloperoxidase em indivíduos tabagistas
- Author
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Martins, André Bittencourt [UNESP], Universidade Estadual Paulista (Unesp), Fonseca, Luiz Marcos da [UNESP], and Farias, Valdecir Ximenes [UNESP]
- Subjects
CXIL8 ,Myeloperoxidase ,Neutrophils ,Neitrófilos ,Fumantes de cigarro ,Mieloperoxidase - Abstract
Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-29Bitstream added on 2014-06-13T18:29:59Z : No. of bitstreams: 1 martins_ab_me_arafcf.pdf: 992180 bytes, checksum: 3281d39ebadb109f527844b299d91644 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Níveis séricos elevados de mieloperoxidase (MPO) estão associados com disfunção endotelial e risco aumentado de acidente cárdio-vascular. Há muito tempo se sabe que o hábito do tabagismo é um fator de risco para doenças cardiovasculares.Uma vez que o infarto do miocárdio está associado também com leucocitose neutrofílica, e fumantes apresentam neutrofilia, nós hipotetizamos que o nível sérico de MPO em fumantes também poderia estar elevado. O estudo incluiu quarenta adultos voluntários e saudáveis. O grupo controle foi composto por vinte indivíduos não tabagistas e o grupo de estudo por vinte indivíduos tabagistas. Hemograma, Interleucina 8 (CXIL8) sérica e MPO sérica foram determinados. Encontramos contagens de neutrófilos e monócitos aumentados (p
- Published
- 2010
44. Apocinina e metóxi-catecóis correlatos: relação entre estrutura molecular e inibição da ativação do complexo NADPH oxidase
- Author
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Kanegae, Marília Pyles Patto [UNESP], Universidade Estadual Paulista (Unesp), Ximenes, Valdecir Farias [UNESP], and Fonseca, Luiz Marcos da [UNESP]
- Subjects
Estrutura molecular ,Citocinas ,Apocynin ,Apocinina - Abstract
Made available in DSpace on 2014-06-11T19:30:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-19Bitstream added on 2014-06-13T19:40:39Z : No. of bitstreams: 1 kanegae_mpp_dr_arafcf.pdf: 355186 bytes, checksum: d30a57da9f59ce845b56a723cbd4b539 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) A apocinina, um métoxi-catecol (MC) extraído das raízes da planta Picrorhiza kurroa, é um eficiente inibidor do complexo NADPH oxidase (NOX) e seu mecanismo de ação está relacionado à inibição da agregação dos componentes enzimáticos e à oxidação catalisada por peroxidases. Estudamos a relação estrutura-atividade da apocinina e de metóxi-catecóis correlatos, na inibição da NOX. Com a função de alterar o potencial de redução das moléculas estudadas, escolhemos MC com grupos adicionais aceptores (MC-A) ou doadores de elétrons (MC-D) na posição para, em relação à hidroxila da molécula de apocinina. Os MC-D inibiram mais fracamente a ativação da NOX em neutrófilos ativados quando comparados aos MC-A. Acreditamos que isso se deva à fraca reatividade destes compostos com grupamentos sulfidrila de proteínas, assim, os MC-D são incapazes de oxidar grupos essenciais aos componentes citosólicos da enzima e desta forma, inibir sua ativação. A diapocinina, metabólito gerado após a oxidação da apocinina por peroxidases, foi sintetizada e avaliamos seus efeitos em neutrófilos e leucócitos mononucleares ativados quanto à inibição da ativação da NOX e em leucócitos mononucleares, em relação à liberação de citocinas e expressão do RNAm do componente de membrana gp91phox. Encontramos que a apocinina e a diapocinina inibiram os três fenômenos estudados, embora a diapocinina o tenha feito de modo mais eficiente. Acreditamos que isto possa estar relacionado ao efeito supressor da apocinina e diapocinina sobre a ativação da NADPH oxidase Apocynin, a methoxy catechol (MC) extracted from the roots of Picrorhiza kurroa has been used as an efficient inhibitor of the NADPH oxidase (NOX) complex and its mechanism of action involves the impairment of the assemble process of the enzyme. Here, we studied the structure-activity relationship for apocynin and analogous ortho-methoxy-substituted catechols as inhibitors of the NADPH oxidase. Aiming to alter the reduction potential, the ortho-methoxy-catechol moiety was kept constant and the substituents at para position related to the hydroxyl group were varied. Two series of compounds were employed: methoxy-catechols bearing electron-withdrawing groups (MC-W) and methoxy-catechol bearing electron-donating groups (MC-D). We found that MC-D were weaker inhibitors of the NOX complex in stimulated neutrophils compared to MD-W. We suggest that there is a close relationship between the weak reactivity of MC-D compounds with sulfhydryl residues of proteins and there incapacity in inhibiting NOX activation. Diapocynin is a product generated by peroxidase oxidation of apocynin. Here we synthesized diapocynin and compared its efficacy as NOX inhibitor in peripheral blood mononuclear cells (PBMC) and neutrophils in relation to apocynin. Both drugs were also studied in cytokine release and its influence on gp91phox mRNA expression. We found that diapocynin was a more efficient inhibitor of NOX activation, gp91phox mRNA expression and cytokine release than apocynin. We suggest that these findings could be related to NOX inhibition process
- Published
- 2009
45. Atividade anti-Helicobacter pylori e potencial antioxidante de espécies vegetais do Cerrado brasileiro
- Author
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Bonacorsi, Cibele [UNESP], Universidade Estadual Paulista (Unesp), Raddi, Maria Stella Gonçalves [UNESP], and Fonseca, Luiz Marcos da [UNESP]
- Subjects
Plantas medicinais - Atividade antimicrobiana ,Helicobacter pylori ,Plantas medicinais - Atividade antioxidante ,Plantas medicinais - Citotoxicidade - Abstract
Made available in DSpace on 2014-06-11T19:32:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-26Bitstream added on 2014-06-13T20:24:17Z : No. of bitstreams: 1 bonacorsi_c_dr_arafcf.pdf: 1612486 bytes, checksum: e3e1240594ace242b7b8aee94d64c29a (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Helicobacter pylori é, atualmente, reconhecido como o principal fator de risco para desenvolvimento da gastrite crônica e úlcera péptica. A resposta inflamatória decorrente da infecção por essa bactéria induz alterações patológicas no microambiente gástrico, com a liberação de citocinas e de grande quantidade de espécies reativas de oxigênio (EROs) por células inflamatórias, especialmente neutrófilos, que contribuem para a injúria da mucosa e desenvolvimento de câncer gástrico. Neste trabalho, a citotoxicidade basal, atividade anti-H. pylori e antioxidante de extratos (apolares e polares), frações, mistura de triterpenos (- amirina e -amirina) e compostos fenólicos (amentoflavona, (+)-catequina, galato de metila, quercetina-3-O--L-arabinopiranosídeo e quercetina-3-O--D-galactopiranosídeo) obtidos de plantas do Cerrado brasileiro, empregadas popularmente no tratamento de distúrbios gastrintestinais, foram determinadas pela técnica do vermelho neutro, microdiluição em caldo, redução do radical 1,1-difenil-2-picril-hidrazila (DPPH) e quimiluminescência dependente de luminol, respectivamente. As preparações vegetais (extratos, frações e mistura de triterpenos) apresentaram baixo potencial citotóxico para a linhagem celular empregada (McCoy). Dentre os compostos fenólicos, quercetina (padrão comercial) e (+)-catequina apresentaram maior citotoxicidade quando comparadas aos extratos, frações e mistura de triterpenos. As espécies Byrsonima crassa (Malpighiaceae) e Davilla elliptica (Dilleniaceae) demonstraram maior potencial para o tratamento de doenças induzidas pelo H. pylori por proporcionarem maior atividade antibacteriana (concentração mínima inibitória = 1024 g/mL), entretanto frações enriquecidas e substâncias isoladas não foram conclusivas para o reconhecimento de grupos ou compostos que pudessem inferir a mesma capacidade... Helicobacter pylori is a bacterium recognized as the major cause of chronic gastritis and peptic ulcer. The H. pylori infection induces an inflammatory response and pathological changes in the gastric microenvironment. The host immune cells (especially neutrophils) release inflammatory mediators and large amounts of reactive oxygen species (ROS), which are related to an increased risk of developing gastric cancer. In this study, we evaluated the basal cytotoxicity, anti-H. pylori and antioxidant activities of extracts (apolar and polar), fractions, mixture of triterpenes (-amirin and -amirin) and phenolic compounds (amentoflavone, (+)-catechin, methyl gallate, quercetin 3-O--L-arabinopyranoside and quercetin-3-O--D-galactopyranoside) obtained from Brazilian Cerrado plants used to treat gastrointestinal disorders, by neutral red uptake assay, broth microdilution method, 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical and luminol-dependent chemiluminescence assays, respectively. A low basal cytotoxicity was showed by the vegetal preparations (extracts, fractions and mixture of triterpenes). Among the phenolic compounds tested, quercetin (commercial standard) and (+)-catechin demonstrated higher cytotoxicity as compared to extracts, fractions and mixture of triterpenes. The Byrsonima crassa (Malpighiaceae) and Davilla elliptica (Dilleniaceae) specie presented greater potential for the treatment of H. pylori-induced gastric pathologies, since they have better antibacterial activity (minimum inhibitory concentration = 1024 g/mL). However, fractions and isolated compounds were not conclusive to identify substances that could be accountable for the antimicrobial activity of the extracts. The antioxidant activity in vitro (DPPH assay) was not necessarily the same as those observed in the ex vivo assay (luminol-dependent chemiluminescence). Although the poor anti-H. pylori activity... (Complete abstract click electronic access below)
- Published
- 2009
46. Efeito citotóxico do sistema HRP/Indóis em células McCoy in vitro
- Author
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Pereira, Débora Helena [UNESP], Universidade Estadual Paulista (Unesp), Fonseca, Luiz Marcos da [UNESP], and Ximenes, Valdecir Farias [UNESP]
- Subjects
McCoy cells - Cytotoxic effect ,Esterase-6 ,Células McCoy - Efeito citotóxico ,Etil ester - Abstract
Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-07Bitstream added on 2014-06-13T18:29:59Z : No. of bitstreams: 1 pereira_dh_me_arafcf.pdf: 425995 bytes, checksum: 068eeb34dc2b20bf30e7a59473c11414 (MD5) Universidade Estadual Paulista (UNESP) A terapia pró-droga/enzima direcionada por anticorpo (ADEPT) consiste em uma primeira etapa , no direcionamento de uma enzima veiculada por anticorpo à uma célula tumoral. Numa segunda etapa uma pró-droga inócua é administrada, e, na presença da enzima, produz compostos citotóxicos restritos à localização do tumor. O par enzima/pró-droga horseradish peroxidase (HRP)/ ácido 3- indol acético (IAA) tem sido aplicada nas estratégias ADEPT. Nesta combinação, o hormônio de planta não tóxico IAA é ativado para espécies citotóxicas pela ação catalítica da HRP. A elucidação das etapas e produtos da reação IAA/HRP levou uma série de moléculas produto a serem apontadas como responsáveis pelos efeitos citotóxicos sem que, até o presente momento, o mecanismo de citotoxicidade tenha sido elucidado. Nesse trabalho, utilizando-se células McCoy como alvo, foi constatado um efeito citotóxico dose dependente do sistema IAA/HRP, por necrose. Esse efeito é quase completamente abolido com a utilização de substâncias antioxidantes ou em anaerobiose. Também foi estudado o uso de um Ester derivado do IAA, o Etil Ester do IAA, como uma nova combinação citotóxica pró-droga/ enzima. Foi constatado que a HRP isolada não consegue catalizar a oxidação do Etil Ester do IAA na ausência de uma enzima adicional (esterase). Dessa forma, pode-se controlar a citotoxicidade do IAA pelo uso de duas enzimas, HRP e esterase. Finalmente, foram apresentadas evidências da aplicação potencial da tríade: Etil Ester IAA/ esterase/ HRP como uma estratégia potencial para a metodologia ADEPT e correlata. The antibody-directed enzyme pro-drug therapy (ADEPT) in a first stage, it’s directed to an enzyme carried to an antibody to a tumor cell. In a second stage a pro-drug harmless is administered, and in the presence of the enzyme, produces cytotoxic compounds restricted the location of the tumor. The pair enzyme / pro-drug horseradish peroxidase (HRP)/ 3 - indole acetic acid (IAA) has been applied in ADEPT strategies. In this combination, the nontoxic plant hormone nontoxic IAA is activated for cytotoxic species by the action of catalytic HRP. The elucidation of the steps and products of the reaction IAA/ HRP led to a series of product molecules identified as being responsible for cytotoxic effects, without, so far, the mechanism of cytotoxicity has been elucidated. In this work, using cells McCoy as a target, we have seen a cytotoxic effect dosedependent system IAA/ HRP, for necrosis. This effect is almost completely abolished with the use of antioxidant substances or oxygen depletion. We also studied the use of an Ester derived from the IAA, the Ethyl Ester of the IAA, as a new combination cytotoxic pro-drug/ enzyme. We have seen that the HRP alone can not catalyze the oxidation of Ethyl Ester of the IAA in the absence of an additional enzyme (esterase). Thus, we can control the cytotoxicity of the IAA for the use of two enzymes, HRP and esterase. Finally, we showed evidence of the potential application of the triad: Ethyl Ester IAA/esterase/ HRP as a potential strategy for the methodology ADEPT and correlates.
- Published
- 2008
47. Burst oxidativo dos neutrófilos humanos: estudo da influência do polimorfismo do receptor para IgG FeyRIIIb na cooperação com os receptores para complemento
- Author
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Urbaczek, Ana Carolina [UNESP], Universidade Estadual Paulista (Unesp), and Fonseca, Luiz Marcos da [UNESP]
- Subjects
Neutrofilos ,Hematologia ,Oxidative burst ,Burst oxidativo - Abstract
Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-05-09Bitstream added on 2014-06-13T19:13:28Z : No. of bitstreams: 1 urbaczek_ac_me_arafcf.pdf: 941529 bytes, checksum: 018e3c8e75f3ede5618f06630714815e (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Universidade Estadual Paulista (UNESP) Os receptores para a porção Fc das IgG (FcgR) estão amplamente expressos nas células do sistema imune e podem estimular uma variedade de respostas efetoras. Três classes de FcgR são descritas nos humanos: FcgRI, FcgRII e FcgRIII. O neutrófilo expressa constitutivamente as isoformas FcgRIIa (CD32) e FcgRIIIb (CD16), as quais apresentam um polimorfismo funcional decorrente do polimorfismo alélico. No FcgRIIa, a substituição da histidina (H) pela arginina (R) na posição 131 resulta nas variantes polimórficas FcgRIIa- R131 e FcgRIIa-H131, que diferem quanto à capacidade de ligação à IgG2 humana. Quanto ao FcgRIIIb (CD16), o polimorfismo genético é responsável pela expressão dos antígenos de neutrófilo (NA)1, NA2 e SH e resulta em um maior número de sítios de glicosilação em NA2. O FcgRIIIb é responsável pela aproximação dos ligantes na membrana para o FcgRIIa e também interage com o receptor para complemento tipo 3 (CR3) na superfície celular. A cooperação entre os FcgRIIa/IIIb com o CR3 promove a estimulação máxima das respostas do neutrófilo, dentre elas o burst oxidativo. Uma vez que a interação FcgRIIIb/CR3 ocorre via sítio de ligação lectina-sacarídeo, o objetivo deste estudo foi avaliar se o polimorfismo alélico do FcgRIIIb poderia afetar a cooperação entre os FcgR e os CR em mediar o burst oxidativo dos neutrófilos. As freqüências dos alelos H/R-131 e NA1/NA2/SH foram analisadas por genotipagem com oligonucleotídeos alelo-específicos e reação em cadeia da polimerase e a densidade de expressão dos receptores (FcgRIIa, FcgRIIIb, CR1 e CR3) foi determinada por citometria de fluxo. A distribuição dos genótipos para o FcgRIIIb (n=169) foi NA1/NA2 (52,1%), NA2 (27,8%) e NA1 (20,1%). Dentre 174 indivíduos, apenas 6,3% apresentaram o gene SH. Quanto aos genótipos para o FcgRIIa (n=143), a distribuição... Receptors for immunoglobulin G (FcgR) are known to be expressed on many cells of the immune system and they can trigger a variety of biological responses. Human FcgR belong to the Ig superfamily and three classes of these receptors have been recognized: FcgRI, FcgRII and FcgRIIl, with different affinities and specificities for IgG subclasses. Neutrophils express the FcgRIIa (CD32) and FcgRIIlb (CD16) isoforms, which display a functional polymorphism due to biallelic polymorphisms. In the case of FcgRIIa, an arginine (FcgRIIa-R131) or histidine (FcgRIIa-H131) at amino acid position 131 determines receptor affinity for IgG2, FcgRIIa-H131 being the isoform with highest affinity. On neutrophils, the FcgRIIIb bears the neutrophil antigen (NA) polymorphism, NA1, NA2 and SH, NA2 being the more glycosylated isoform. Cooperation of FcgRIIIb with FcgRIIa and CR3 (complement receptor type 3) is necessary for efficient neutrophil responses, including the oxidative burst. Since the FcgRIIIb/CR3 cooperation occurs via lectin-sacharide-like interaction, the aim of this study was to evaluate whether the allelic polymorphism, NA1 and NA2, could influence the cooperation of FcgRIIIb with CR3 in mediating the oxidative burst of neutrophils. FcgRIIa and FcgRIIIb genotyping analysis were performed by polymerase chain reaction with allelespecific primers and surface expressions of FcgRIIa, FcgRIIIb, CR1 and CR3 on neutrophils were determined by flow cytometry. The FcgRIIIb genotype distribution (n=169) was NA1/NA2 (52.1%), NA2 (27.8%) and NA1 (20.1%). SH gene was found in 11 (6.3%) volunteers from 174 subjects. With respect to the FcgRIIa genotype (n=143), the distribution observed was R131 (41.2%), H/R131 (38.5%) and H (20.3%). Neutrophils were stimulated with immune complexes (IC)-IgG opsonized or not with complement and the oxidative burst... (Complete abstract click electronic access below)
- Published
- 2008
48. Desenvolvimento de ensaio quimiluminescente baseado na determinação de fosfatase alcalina para diagnóstico diferencial entre leucemia mielóide crônica e reações leucemóides
- Author
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Kanegae, Marília Pyles Patto [UNESP], Universidade Estadual Paulista (Unesp), and Fonseca, Luiz Marcos da [UNESP]
- Subjects
Leukaemoid reactions ,Chemiluminescence ,Leukocyte alkaline phosphatase ,Immulite® ,Quimiluminescencia ,Fosfatase alcalina neutrofílica ,Reações leucemóides ,Leucemia mielóide crônica ,Chronic myeloid leukaemia - Abstract
Made available in DSpace on 2014-06-11T19:26:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2006Bitstream added on 2014-06-13T18:54:35Z : No. of bitstreams: 1 kanegae_mpp_me_arafcf.pdf: 328350 bytes, checksum: ee1587bd6ab853b184cea70a4d71dac0 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Em hematologia, a principal aplicação da determinação da atividade da fosfatase alcalina (FA) neutrofílica é no auxílio ao diagnóstico diferencial entre leucemia mielóide crônica (LMC) e reações leucemóides neutrofílicas (RL) decorrentes de doenças mieloproliferativas, como a mielofibrose, policitemia vera ou de inflamações/ infecções. Tradicionalmente esta determinação é realizada por um ensaio citoquímico subjetivo, no qual se atribui uma pontuação (SCORE) para o nível de FA. Neste trabalho apresentamos um método quimiluminescente, objetivo, quantitativo, sensível e barato para a determinação de FA neutrofílica baseado no reagente comercial Immulite®. Leucócitos íntegros obtidos de amostras de sangue periférico de trinta e dois indivíduos saudáveis, nove portadores de LMC e nove portadores de RL foram submetidos ao protocolo otimizado. Através da determinação da emissão de luz por quatro concentrações de neutrófilos, foi possível detectar a atividade de FA por célula (inclinação - SLOPE - da curva obtida por regressão linear). Uma alta correlação foi obtida quando o método quimiluminescente (SLOPE), aqui desenvolvido, foi comparado ao citoquímico (SCORE). Obtivemos uma variação do SLOPE entre 0,61-8,49 (10-5 mV.s/célula) para amostras do grupo controle (indivíduos saudáveis), sendo que o valor da mediana foi 2,04 (10-5 mV.s/célula). Estes resultados foram estatisticamente diferentes das amostras do grupo LMC (variação: 0,07 - 1,75; mediana: 0,79) e do grupo RL (variação: 3,84 - 47,24; mediana: 9,58) (p
- Published
- 2006
49. Alkyl caffeates as anti-Helicobacter pylori and scavenger of oxidants produced by neutrophils.
- Author
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Paracatu LC, Bonacorsi C, de Farias CM, Nazare AC, Petronio MS, Regasini LO, Silva DH, Raddi MS, da Fonseca LM, and Ximenes VF
- Subjects
- Alkylation, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Humans, Microbial Sensitivity Tests, Reactive Oxygen Species metabolism, Anti-Bacterial Agents pharmacology, Caffeic Acids pharmacology, Helicobacter pylori drug effects, Neutrophils metabolism, Reactive Oxygen Species antagonists & inhibitors
- Abstract
Helicobacter pylori pathogenic action involves the colonization of the gastrointestinal tract and a large production of reactive oxygen species (ROS) by the neutrophils attracted to the site of infection. The aim of this study was to evaluate caffeic acid and its alkyl esters as inhibitors of the release of ROS by Helicobacter pylori activated neutrophils and their bactericidal effect. The increased hydrophobicity caused by esterification had direct consequence in their efficiency as bactericidal agents against H. pylori and inhibitors of the production of ROS by neutrophils. The minimum inhibitory concentration (MIC) decreased from higher than 1000 μg/mL (caffeic acid) to 250 μg/mL to butyl and heptyl caffeate. The release of total ROS, superoxide anion and hypochlorous acid by activated neutrophils was also significantly decreased and the esters were more efficient than the acid precursor. In conclusion, the alkyl esters of caffeic acid have two properties that are complementary for the treatment of H. pylori infections: bactericidal activity and inhibitory effect upon generation of ROS by neutrophils. Hence, we propose that these easily synthesized and non-expensive substances should be applied to in vivo experimental models of H. pylori induced gastric infections.
- Published
- 2014
- Full Text
- View/download PDF
50. Horseradish peroxidase-catalyzed oxidation of rifampicin: reaction rate enhancement by co-oxidation with anti-inflammatory drugs.
- Author
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dos Santos Fde J, Ximenes VF, da Fonseca LM, de Faria Oliveira OM, and Brunetti IL
- Subjects
- Animals, Antitubercular Agents pharmacokinetics, Antitubercular Agents pharmacology, Catalysis, Oxidation-Reduction, Rifampin pharmacokinetics, Rifampin pharmacology, Anti-Inflammatory Agents pharmacology, Antitubercular Agents metabolism, Horseradish Peroxidase metabolism, Rifampin metabolism
- Abstract
The tuberculostatic drug rifampicin has been described as a scavenger of reactive species. Additionally, the recent demonstration that oral therapy with a complex of rifampicin and horseradish peroxidase (HRP) was more effective than rifampicin alone, in an animal model of experimental leprosy, suggested the importance of redox reactions involving rifampicin and their relevance to the mechanism of action. Hence, we studied the oxidation of rifampicin catalyzed by HRP, since this enzyme may represent the prototype of peroxidation-mediated reactions. We found that the antibiotic is efficiently oxidized and that rifampicin-quinone is the product, in a reaction dependent on both HRP and hydrogen peroxide. The steady-state kinetic constants Km(app) (101+/-23 micromol/l), Vmax(app) (0.78+/-0.09 micromol/l.s(-1)) and kcat (5.1+/-0.6 s(-1)) were measured (n=4). The reaction rate was increased by the addition of co-substrates such as tetramethylbenzidine, salicylic acid, 5-aminosalicylic acid and paracetamol. This effect was explained by invoking an electron-transfer mechanism by which these drugs acted as mediators of rifampicin oxidation. We suggested that this drug interaction might be important at the inflammatory site.
- Published
- 2005
- Full Text
- View/download PDF
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