Banca de DEFESA: GUSTAVO NUNES DE SANTANA CASTRO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : GUSTAVO NUNES DE SANTANA CASTRO
DATE: 16/02/2022
TIME: 13:30
LOCAL: Google meet
TITLE:

Evaluation of the anti-inflammatory and antinociceptive activities of the synthetic compound ((2S,6S)-6-ethyl-tetrahydro-2H-pyran-2-yl)methanol in mice

KEY WORDS:

Tetrahydropyran derivatives, acute inflammation, mice, cytokines, acute nociception.

PAGES: 108
BIG AREA: Ciências Agrárias
AREA: Medicina Veterinária
SUBÁREA: Clínica e Cirurgia Animal
SPECIALTY: Farmacologia e Terapêutica Animal
SUMMARY:

Pain and inflammation can be generated by a multitude of stimuli, being very common entities in veterinary medicine, for this reason analgesics and anti-inflammatory drugs are the most prescribed drugs during clinical routine. It is important to note that the main classes of these drugs are associated with important side effects. Several drugs in common use were discovered during experimental tests and through observation in animals. When a new compound appears promising, it usually undergoes changes in its chemical structure in order to improve its selectivity, potency and therapeutic efficacy. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of a new synthetic compound ((2S,6S)-6-ethyl-tetrahydro-2H-pyran-2-IL) methanol (LS20) prepared from a previous prototype, acid (±)-cis-(6-ethyltetrahydropyran-2-yl) formic. Compound LS20 was evaluated in acute pain induction assays. Oral administration of the compound was able to induce antinociceptive activity in models of abdominal writhing induced by acetic acid, formalin (in both phases), tail flick and hot plate. To elucidate the mechanism of action of the compound, the tail docking model was used. In this model, prior administration of naloxone (non-selective opioid antagonist) was performed, in which inhibition of the effect produced by the compound was observed. Thus, the selective participation of opioid receptors (μ, δ and κ) was evaluated through previous administration of methylnaltrexone, naltrindol and nor-binaltorphimine, respectively, where all antagonists were able to reduce the antinociceptive effect of the compound. To evaluate the possible participation of the nitrergic, cholinergic and serotonergic pathways, the animals were pre-treated with L-NAME (non-selective nitric oxide synthase inhibitor), L-arginine (nitric oxide precursor), atropine (muscarinic cholinergic receptor antagonist). ), mecamylamine (nicotinic cholinergic receptor antagonist), ondansetron (5-HT3 serotonin receptor antagonist) and PCPA (serotonin synthesis inhibitor). The Rotarod model was used to evaluate the possibility of interference of motor performance on the antinociceptive effect, it was demonstrated the absence of this interference. As for the anti-inflammatory activity, the result in the paw edema test indicates an antiedematogenic effect of the compound. There was a decrease in the amount of total leukocytes, indicating that the compound was able to reduce leukocyte migration in the inflammation existing in the subcutaneous air pocket. The compound also showed inhibitory activity on the production of TNF-α, IL-1beta and IL-6, but did not show any change in IL-10 levels. Regarding the in vitro assays, there was no cytotoxicity, and a reduction in the concentrations of TNF-α and IL-6, but there was no change in the production of nitric oxide. The anti-inflammatory activity was also evaluated in vitro, it was observed the selective inhibition of the COX-2 enzyme. These results indicate significant antinociceptive activity of the compound, without evidence of motor impairment. The LS20 compound demonstrated a central antinociceptive effect, the latter having a non-selective contribution from the opioid systems. And yet, anti-inflammatory activity, with inhibition of leukocyte migration, of TNF-α and IL-1beta and IL-6, in addition to selective inhibitory activity on COX-2.

BANKING MEMBERS:
Interno - 1674073 - BRUNO GUIMARAES MARINHO
Interna - 2193086 - MAGDA ALVES DE MEDEIROS
Externo ao Programa - 3000663 - DAVID DO CARMO MALVAR
Externo à Instituição - CARLOS GIOVANI DE OLIVEIRA NASCIMENTO - UNIFAL-MG
Externo à Instituição - LUIS FELIPE SOUZA DA SILVA - UFS