Potential anti-inflammatory effect of LQFM-021 in carrageenan-induced inflammation: The role of nitric oxide

• Published in: Nitric oxide 2017-09, Vol.69, p.35-44
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Carrageenan; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cytokines; Cytokines - metabolism; Dinoprostone - metabolism; Indomethacin - pharmacology; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Leukocyte Count; LQFM-021; Male; Mice; NG-Nitroarginine Methyl Ester - pharmacology; Nitrates - analysis; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitrites - analysis; Peroxidase - metabolism; Pleurisy - chemically induced; Pleurisy - drug therapy; Pleurisy - metabolism; Pyrazole compound; Pyrazoles - pharmacology; Tetrazoles - pharmacology; Up-Regulation
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2017.04.006

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.