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Florentino, Iziara F.; Silva, Daiany P.B.; Silva, Dayane M.; Cardoso, Carina Sofia; Moreira, André L.E.; Borges, Clayton L.; Soares, Célia M. de A.; Galdino, Pablinny M.; Lião, Luciano M.; Ghedini, Paulo C.; Menegatti, Ricardo; Costa, Elson A.
Nitric oxide, 09/2017, Volume: 69Journal Article
The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activities. Furthermore, it has low toxicity, indicating that this compound may be considered to be a good prototype for the development of new analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to investigate the potential anti-inflammatory activity of LQFM-021 using a model of carrageenan-induced inflammation as well as the mechanism of action and role of nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.) reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as decreased protein extravasation and myeloperoxidase activity. This dose of LQFM-021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF-α and IL-1β levels in the pleural cavity. Moreover, pre-treatment with L-NAME reversed the effect of LQFM-021 on NO, leukocyte migration, and the TNF-α and IL-1β levels. Additionally, we observed that LQFM-021 showed weak inhibitory activity on cyclooxygenases, but reduced the PGE2 levels in the pleural cavity. Immunoblot analyses showed that LQFM-021 promoted a decrease in COX-2 levels and increase in iNOS levels. In conclusion, we demonstrated that LQFM-021 has marked anti-inflammatory activity by reducing polymorphonuclear recruitment, which is associated with the inhibition of the production of inflammatory cytokines and eicosanoids. In addition, we found that the synthase/release of nitric oxide promoted by LQFM-021 is essential for the anti-inflammatory effect observed. Display omitted •Anti-inflammatory activity of LQFM-021 in carrageenan-induced inflammation models.•LQFM-021 inhibition of the production of inflammatory cytokines and eicosanoids.•LQFM-021 increased the NO (nitrite/nitrate) in pleural exudate.•Role of nitric oxide in the anti-inflammatory activity of LQFM-021.
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