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

Abstract

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.

• Authors: Iziara F Florentino, Daiany P B Silva, Dayane M Silva, Carina Sofia Cardoso, André L E Moreira, Clayton L Borges, Célia M de A Soares, Pablinny M Galdino, Luciano M Lião, Paulo C Ghedini, Ricardo Menegatti, Elson A Costa
• Journal: Nitric oxide : biology and chemistry (Nitric Oxide) Vol. 69 Pg. 35-44 (Sep 30 2017) ISSN: 1089-8611 [Electronic] United States
• PMID: 28412475 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Cytokines
• Nitrates
• Nitrites
• Pyrazoles
• Tetrazoles
• Nitric Oxide
• Carrageenan
• Peroxidase
• Nitric Oxide Synthase Type II
• Cyclooxygenase 1
• Dinoprostone
• NG-Nitroarginine Methyl Ester
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Carrageenan
• Cyclooxygenase 1 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Indomethacin (pharmacology)
• Inflammation (chemically induced, drug therapy, metabolism)
• Leukocyte Count
• Male
• Mice
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitrates (analysis)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics)
• Nitrites (analysis)
• Peroxidase (metabolism)
• Pleurisy (chemically induced, drug therapy, metabolism)
• Pyrazoles (pharmacology)
• Tetrazoles (pharmacology)
• Up-Regulation