Banca de QUALIFICAÇÃO: JOHNY WYSLLAS DE FREITAS OLIVEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : JOHNY WYSLLAS DE FREITAS OLIVEIRA
DATE: 06/10/2022
TIME: 08:30
LOCAL: Videoconferência - Link para acesso: meet.google.com/ksa-oohr-azw
TITLE:

PHARMACOLOGICAL AND BIOCHEMICAL CHARACTERIZATION OF SODIUM DIETHYLDITIOCARBAMATE AS A POTENTIAL DRUG FOR THE THERAPEUTIC OF CHAGAS DISEASE AND LEISHMANIASIS

KEY WORDS:

Antiparasitic activity; Trypanosoma cruzi; Leishmania sp. and nanoformulations

PAGES: 135
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Chagas Disease and Leishmaniasis are endemic zoonosis in several parts of the planet and affect mainly poor regions. The drugs disponible to treat both diseases present low efficacy towards intracellular forms, high toxicity, low bioavailability and are not safe to health patient. So, a several decades searches are developed to find new drugs and compounds used against those diseases. A promisor candidate is the sodium diethyldithiocarbamate recently described as a compound with high efficacy against Leishmania sp. and T. cruzi using in vitro and in vivo models, meantime, the advanced in technology search new tools to increase bioavailability of this compound and characterize its biological response. The focus of this work was evaluating the DETC nanosystem production, its application against T. cruzi and Leishmania sp. using in vitro and in vivo models, as well as, evaluate the free DETC against T. cruzi e Leishmania sp. in vivo model. First was evaluated the physical and chemical parameters of nanosystem PLA-DETC production, in addition was evaluated the cytotoxicity against cells, pass through cell barriers, the in vitro antiparasitic activity against different strains of T. cruzi and Leishmania infantum and Leishmania amazonensis, and lastly was evaluated the reactive oxygen species production when parasite was expose to the compound. It was observed that PLA-DETC is a stable nanoparticle with diameter <200nm and PDI <0,3 and zeta potential equal to -20 mV, in addition present low toxicity towards cell lines and high capacity to penetrate cell using 3T3 and RAW cell lines when exposed for 24 hours. The antiparasitic activity of PLA-DETC achieve 70% when put together with Dm28c strain of T. cruzi and 65% against L. amazonensis in 24 hours. Futhermore in ROS production was evaluated increases that reach 70% whern compared against control. After in vitro evaluation, was performed the in vivo toxicity both the PLA-DETC nanoparticle and free DETC in concentrations of 300 mg/kg and 1000mg/kg, the hematologic, biochemistry, histopathology and hemolytic parameters were dimensioned, to determinate acute toxicity was preconized the test 423 disponible by OECD. From the results, very few changes were observed compared to the control group, firstly, a 10% reduction in platelet levels was observed, a slight increase in urea and AST, with a reduction in creatine levels, in addition, there was nosignificant change in the weight of the animals that followed the same pattern as the control group, as well as no change in the behavior of the animals.Finally, the profiles of infection of Chagas disease in Balb/C mice were evaluated, which was verified and confirmed the peak of the parasite concentration in the blood, in addition to using serological markers such as ELISA for confirmation.However, to complete this work, the characterization of the antiparasitic activity of DETC and of the PLA-DETC nanoparticle against T. cruzi and Leishmania sp.in a murine model.

COMMITTEE MEMBERS:
Externo ao Programa - 2611909 - CARLOS RAMON DO NASCIMENTO BRITO - nullPresidente - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Interno - 2985070 - JONAS IVAN NOBRE OLIVEIRA