Banca de DEFESA: LIVIAN RABELO LOPES

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LIVIAN RABELO LOPES
DATE: 05/09/2022
TIME: 14:00
LOCAL: Google Meet - https://meet.google.com/gia-ardp-kro
TITLE:

Drug repositioning: evaluation of the anti-inflammatory and antinociceptive activity of nitazoxanide

KEY WORDS:

nitazoxanide, drug repositioning, anti-inflammatory, antinociceptive, paw edema, TNF-α

PAGES: 72
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Nitazoxanide (NTZ) is a drug widely used for the treatment of a wide variety of parasitic diseases. Some recent discoveries suggest new therapeutic functions of this drug, a process called drug repositioning. New drug development is a slow and costly process, so drug repositioning is an effective alternative approach. Inflammatory processes are part of the pathogenesis of several very prevalent diseases. Inflammation is a complex biological process and its chronicity can lead to deleterious effects in the body. The treatment of inflammation involves the use of non-steroidal anti-inflammatory drugs, glucocorticoids and opioids, but the prolonged use of these drugs can cause serious adverse effects. Therefore, the search for new safer drugs is necessary. The objectives of this work were to evaluate the anti-inflammatory and antinociceptive activities of NTZ; using experimental models of paw edema induced by carrageenan (Cg), model of abdominal writhing induced by acetic acid, formalin test and rota rod for analysis of motor impairment and balance. The oral (po) treatment of the animals with NTZ  induced a significant inhibition of paw edema of 60% and 68% at doses of 10 and 30 mg/Kg, respectively, already in the first hour after Cg injection. There was also a significant inhibition 3 and 4 hours after the inflammatory stimulus at doses of 10 mg/Kg (57.14% and 21.27%) and 30 mg/Kg (69.25% and 61.70%) and 6 hours after stimulation at a dose of 30 mg/kg (40.47%). Histological analysis of the footpads of animals treated with NTZ 30 mg/Kg (4 hours after Cg stimulation) showed a reduction in the migration of inflammatory cells by 65.77%. Likewise, treatment with NTZ 30 mg/Kg reduced tumor necrosis factor-α (TNF-α) levels in the footpad 2 hours after Cg-induced inflammation. NTZ showed antinociceptive activity, significantly inhibiting the number of abdominal contortions induced by acetic acid at doses of 30 and 90 mg/kg by 54.14% and 56.21%, respectively. In the formalin test, doses of 10 and 30 mg/Kg did not present an antinociceptive effect; and the dose of 90 mg/Kg had an effect in both phases of the test (55.88% and 57.99%). Finally, the treatment of animals with NTZ, at doses of 10, 30 and 90 mg/Kg, did not cause any motor or balance alteration in the rota rod test. This result suggests that the antinociceptive effect of NTZ may be related to the reduction of inflammatory pain by inhibiting inflammation. The results suggest an anti-inflammatory effect, possibly related to the decrease in TNF-α.

BANKING MEMBERS:
Presidente - 1741307 - ADRIANA CRISTINA SOARES DE SOUZA
Interna - 2144084 - PRISCILA TOTARELLI MONTEFORTE
Externa à Instituição - MELISSA GRAZIELLE MORAIS - UEMG