| Grant number: | 07/02487-3 |
| Support Opportunities: | Regular Research Grants |
| Start date: | March 01, 2008 |
| End date: | February 28, 2010 |
| Field of knowledge: | Health Sciences - Pharmacy - Medicines Analysis and Control |
| Principal Investigator: | Yara Maria Lucisano Valim |
| Grantee: | Yara Maria Lucisano Valim |
| Host Institution: | Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
Abstract
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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