Banca de DEFESA: NORTON RUBENS DIUNIOR LUCAS PEJARA ROSSI

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : NORTON RUBENS DIUNIOR LUCAS PEJARA ROSSI
DATE: 26/04/2024
TIME: 12:30
LOCAL: Sala Virtual Remota - https://bit.ly/DefDoc_NortonRossi_PGBIOEXP
TITLE:

Susceptibility of Leishmania (Leishmania) amazonensis to antimalarials: An alternative for the in vivo study of drug repositioning 2024. Thesis (Doctorate in Experimental Biology) – Postgraduate Program in Experimental Biology, Federal University of Rondônia, Rondônia, 2024.

KEY WORDS:

Leishmania (L.) amazonensis, antimalarial, leishmanicidal, drug combination.

PAGES: 108
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Leishmaniases are endemic parasitic diseases of concern to Brazilian public health. The state of Rondônia is an area where the disease is transmitted, with an average incidence of 721 cases between the years 2018 and 2022. The limitations of treatments for this disease, the increasing resistance, and the therapeutic failure associated with some species are important aspects indicating the urgency of new therapeutic drugs. Repurposing drugs with confirmed action against other protozoa can accelerate the discovery of alternative therapies for leishmaniasis and expand the market for products whose toxicological description has already been submitted to drug regulatory authorities. Recent in vitro tests against Leishmania promastigotes and amastigotes, conducted by our group of researchers, have shown leishmanicidal action of some antimalarials, which led to the design of this study. The aim of this study is to evaluate the in vivo susceptibility profile of Leishmania (Leishmania) amazonensis to antimalarials alone or in combination with the reference drug amphotericin B. By infecting Balb/c mice with the parasite, it was possible to assess the parasitic load of the paw lesion, obtaining the effective dose for 50% parasite death (ED50) of amphotericin B (0.63 mg/kg), artesunate (3.13 mg/kg), and chloroquine (27.29 mg/kg). With these data, combinations of antimalarials with amphotericin B were performed, yielding contrasting results. While the combination with artesunate resulted in increased parasitemia, the combination with chloroquine led to a decrease. The latter, although not resulting in complete cure, was statistically equivalent to the naive group. In this study, the dosage of biochemical metabolites and serum cytokines was quantified using commercial kits. Both antimalarials showed no toxicity at the ED50 dosage. As a result of quantifying these cytokines, it was observed that artesunate elicited an immune response similar to the untreated infection group, whereas chloroquine, despite exhibiting anti-inflammatory activity, was effective in increasing IFN-γ production. The prospects of this study are to expand the alternatives of chemotherapeutic formulations and foresee the rational use of drugs to overcome existing limitations.

COMMITTEE MEMBERS:
Externa à Instituição - KARINE MODOLON ZEPON - UNISUL/SC
Externo à Instituição - IRLON MACIEL FERREIRA - UNIFAP
Externo à Instituição - ALEJANDRO FERRAZ DO PRADO - UFPA
Presidente - ***.429.088-** - CAROLINA BIONI GARCIA TELES - FIOCRUZ
Externa à Instituição - DANIELLE LAZARIN BIDÓIA - UEL