Comparison of the effect of dipyrone and carprophen on inflammatory infiltrate through immunophenotyping synovial cells in an Arthritis model in rats

• Grant number: 21/08253-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2021
• End date: September 30, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Cristina de Oliveira Massoco Salles Gomes
• Grantee: Fernanda de Brito Utuari
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In the treatment of chronic pain in domestic animals, such as osteoarthrosis, nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of pharmacological treatment usually associated with analgesics. The mechanism of action of these drugs is still being explored, while the best known is through the inhibition of cyclooxygenase(COX), an essential enzyme for the production of eicosanoids in cell membranes, a fundamental component of the inflammatory cascade. Within this pharmacological group, we have carprofen, an NSAID with limited COX inhibitory action, but which has potent analgesic and anti-inflammatory properties, with minimal adverse effects, due to its high selectivity for COX-2. Another drug classified as NSAID is dipyrone, an antiinflammatory that, unlike the others, has a good analgesic effect associated with a less potent anti-inflammatory action, which is due to its differentiated mechanism of action, based on the inhibition of a cyclooxygenase central, COX-3. In order to study new drugs and understand the mechanism of known drugs in inflammatory diseases, an excellent experimental model is the classic model of monoarthritis induction in rats, which is performed by intra-articular inoculation of complete Freund's adjuvant, mineral oil containing an inactive mycobacterium (Mycobacterium tuberculosis or inactive Mycobacterium butyricum). Due to the cellular characteristics of the inflammatory process, CD62L positive cells, nitric oxide, PGE2, and CD4+ and CD8+ lymphocytes are indicative markers of the inflammatory process in this model of monoarthritis in rats. To carry out this study, 40 Wistar rats will be used, divided into 4 treatment groups, two groups with dipyrone at different concentrations associated with tramadol, one with carprofen also associated with tramadol, and the other with tramadol only. From the synovial fluid, the frequency of inflammatory cells will be evaluated, as well as the quantification of PGE2 and nitric oxide. To assess the evolution of the inflammatory process after induction and treatment, computed tomography [18F] FDG PET/CT will be performed. This project aims to investigate whether dipyrone has an antiinflammatory effect of the same magnitude as carprofen. (AU)