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| Author(s): |
Luciana Mariko Kabeya
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2002-06-21 |
| Examining board members: |
Yara Maria Lucisano Valim;
Ivone Carvalho;
Carlos Alberto de Oliveira
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| Advisor: | Yara Maria Lucisano Valim |
| Abstract | |
Neutrophils play a crucial role in the defense of the organism against invading microorganisms, thorough phagocytosis, degranulation and generation of reactive oxygen species (EROS). The last one is a consequence of activation of neutrophils\' oxidative metabolism. The produced EROs, such as O2∙-, H2O2, HOCl, HO∙, 1O2 and NO, which are essential for killing phagocyted microorganisms, may also be released to the extracellular milieu and inflict oxidative damage to host tissues. This damage has been implicated in the pathogenesis of diseases, such as arteriosclerosis, cancer, rheumatoid arthritis, pneumonia and lung emphysema. The antioxidant activity of many compounds, especially those obtained from plants, has been investigated with the aim of avoid such oxidative damage. In this work, we studied the activity of eight simple coumarins (compounds 1 to 8) on the oxidative metabolism of rabbit neutrophils upon stimulation by opsonized zymosan, using luminol- (QLlum) and lucigenin (QLluc)-enhanced chemiluminescence (QL) assays. QLluc reflects generation of O2∙- only, whereas QLlum is a result of luminol oxidation by the various EROs produced by the stimulated neutrophils. Inhibition of QLluc and of QLlum will be a consequence of the decrease of the concentration of that EROs which are involved in the oxidation of lucigenin and luminol, respectively, in the reaction medium. We also evaluated the activity of the antioxidants a-tocopherol, butyl-hydroxytoluene (BHT) and quercetin on QLlum and QLluc, and the toxicity of coumarins 1 to 8 and the three antioxidants on rabbit neutrophils. Partition coefficient and molecular volume values of coumarins 1 to 8 were determined. We observed that, among the three antioxidants, quercetin inhibited QLlum and QLluc, and was not toxic to the neutrophils at concentration of 50 mmol/L. BHT was toxic to the rabbit neutrophils whereas a-tocopherol did not inhibit QLlum nor QLluc. For the simple coumarins we observed that: (1) coumarin 1 did not inhibit QLlum nor QLluc; (2) coumarins 3, 4, 5 and 6 had inhibitory effects, which were similar to the quercetin and higher than coumarins 2, 7 and 8; (3) the inhibitory activities of coumarins 2 to 8 on QLluc were not related to the lipophilicity and to the molecular volume of these compounds, nor to their toxicity upon the rabbit neutrophils; (4) coumarins 3 and 4 increased the QLlum, whereas the others had no effect on this system. (AU) | |