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Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions

Grant number: 07/00840-8
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2008
Effective date (End): June 30, 2011
Field of knowledge:Health Sciences - Pharmacy - Medicines Analysis and Control
Principal Investigator:Yara Maria Lucisano Valim
Grantee:Luciana Mariko Kabeya
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Neutrophils are essential cells for the body defense against invading microrganisms, by acting through phagocytosis, lysosomal enzyme release and reactive oxygen species (ROS) generation. The last function is mediated by the NADPH oxidase complex, which produces superoxide anion, and by myeloperoxidase (MPO), which generates halogenated reactive species such as HOCl. In some inflammatory diseases, as rheumatoid arthritis and Chron disease, characterized by increased neutrophil infiltration and MPO concentrations, an increased ROS production and tissue oxidative damage were also detected at the inflammatory site. In this context, modulation of MPO activity by phenolic compounds has been widely investigated with the purpose of supressing the tissue damage. In addition to the microbicidal function, MPO has been recently described to participate in the metabolization of hydroxylated drugs and contribute to modulate their therapeutic efficacy. However, MPO-catalyzed reactions can also generate free radicals and quinones with pro-oxidant properties, that contribute to increase the tissue oxidative stress. Previous results from our research group show that hydroxylated coumarin derivatives can have anti- or pro-oxidant properties in horseradish peroxidase-catalyzed reactions. However, there are no reports about the biological effects of such coumarin derivatives in MPO-mediated reactions, whether they enhance or supress the ROS generation, as well as their influence on the tissue oxidative stress and modulation of leukocyte effector functions. (AU)

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
KABEYA, LUCIANA M.; ANDRADE, MICASSIO F.; PIATESI, FABIANA; AZZOLINI, ANA ELISA C. S.; POLIZELLO, ANA CRISTINA M.; LUCISANO-VALIM, YARA MARIA. 3,3 `,5,5 `-Tetramethylbenzidine in hypochlorous acid and taurine chloramine scavenging assays: interference of dimethyl sulfoxide and other vehicles. Analytical Biochemistry, v. 437, n. 2, p. 130-132, . (07/02487-3, 07/00840-8)
SANTOS, EVERTON O. L.; KABEYA, LUCIANA M.; FIGUEIREDO-RINHEL, ANDREA S. G.; MARCHI, LARISSA F.; ANDRADE, MICASSIO F.; PIATESI, FABIANA; PAOLIELLO-PASCHOALATO, ADRIANA B.; AZZOLINI, ANA ELISA C. S.; LUCISANO-VALIM, YARA M.. Flavonols modulate the effector functions of healthy individuals' immune complex-stimulated neutrophils: A therapeutic perspective for rheumatoid arthritis. International Immunopharmacology, v. 21, n. 1, p. 102-111, . (07/00161-3, 07/00840-8, 06/04398-5, 07/06925-5, 07/02487-3)
PAOLIELLO-PASCHOALATO, ADRIANA BALBINA; MARCHI, LARISSA FAVARO; DE ANDRADE, MICASSIO FERNANDES; KABEYA, LUCIANA MARIKO; DONADI, EDUARDO ANTONIO; LUCISANO-VALIM, YARA MARIA. Fc gamma and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products. Evidence-based Complementary and Alternative Medicine, . (12/23541-4, 07/00840-8, 13/20810-7, 07/02487-3)
RODRIGUES, LILIAN CATALDI; SECATTO, ADRIANA; SORGI, CARLOS A.; DEJANI, NAIARA N.; MEDEIROS, ALEXANDRA I.; BORGES PRADO, MORGANA KELLY; RAMOS, SIMONE GUSMAO; CUMMINGS, RICHARD D.; STOWELL, SEAN R.; FACCIOLI, LOCIA HELENA; et al. Protective Effect of Galectin-1 during Histoplasma capsulatum Infection Is Associated with Prostaglandin E-2 and Nitric Oxide Modulation. Mediators of Inflammation, . (11/17611-7, 07/02487-3, 07/00840-8)
KABEYA, LUCIANA M.; FUZISSAKI, CAROLINA N.; TALEB-CONTINI, SILVIA H.; FERREIRA, ANA MARIA DA C.; NAAL, ZEKI; SANTOS, EVERTON O. L.; FIGUEIREDO-RINHEL, ANDREA S. G.; AZZOLINI, ANA ELISA C. S.; VERMELHO, ROBERTA B.; MALVEZZI, ALBERTO; et al. 7-Hydroxycoumarin modulates the oxidative metabolism, degranulation and microbial killing of human neutrophils. Chemico-Biological Interactions, v. 206, n. 1, p. 63-75, . (05/60596-8, 07/00840-8, 07/02487-3)
KABEYA, LUCIANA M.; FUZISSAKI, CAROLINA N.; ANDRADE, MICASSIO F.; AZZOLINI, ANA ELISA C. S.; TALEB-CONTINI, SILVIA H.; VERMELHO, ROBERTA B.; LOPES, JOAO LUIS C.; LUCISANO-VALIM, YARA MARIA. 4-Methylcoumarin Derivatives Inhibit Human Neutrophil Oxidative Metabolism and Elastase Activity. JOURNAL OF MEDICINAL FOOD, v. 16, n. 8, p. 692-700, . (07/02487-3, 07/00840-8)
ANDRADE, MICASSIO F.; KABEYA, LUCIANA M.; AZZOLINI, ANA ELISA C. S.; SANTOS, EVERTON O. L.; FIGUEIREDO-RINHEL, ANDREA S. G.; PARIS, MARCIO R. P.; EMERY, FLAVIO S.; PUPO, MONICA T.; LUCISANO-VALIM, YARA M.. 3-Phenylcoumarin derivatives selectively modulate different steps of reactive oxygen species production by immune complex-stimulated human neutrophils. International Immunopharmacology, v. 15, n. 2, p. 387-394, . (09/14184-0, 07/02487-3, 07/00840-8)
FIGUEIREDO-RINHEL, ANDREA S. G.; SANTOS, EVERTON O. L.; KABEYA, LUCIANA M.; AZZOLINI, ANA ELISA C. S.; SIMOES-AMBROSIO, LIVIA M. C.; LUCISANO-VALIM, YARA M.. The Flavonols Quercetin, Myricetin, Kaempferol, and Galangin Inhibit the Net Oxygen Consumption by Immune Complex-Stimulated Human and Rabbit Neutrophils. ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES, v. 69, n. 7-8, p. 346-356, . (07/00840-8)

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