Banca de DEFESA: THALINE MABEL SOUSA SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : THALINE MABEL SOUSA SANTOS
DATE: 20/12/2021
TIME: 13:00
LOCAL: IGM Sala Virtual 5
TITLE:

Use of hydroxylamine and DETC association in the treatment of leishmaniasis in vitro

KEY WORDS:

Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Leishmania braziliensis; Leishmania mexicana amazonensis; Leishmania (Leishmania) infantum; Ditiocarb; Hydroxylamine.

PAGES: 61
BIG AREA: Ciências Biológicas
AREA: Parasitologia
SUMMARY:

ABSTRACT INTRODUCTION: Leishmaniasis are a group of neglected diseases, according to the World Health Organization, that affects one billion of people that are at risk of infection. Clinical status vary according to the parasite species and the host immune response and genetic background. The most used drugs to the treatment of leishmaniasis are pentavalent antimonials. However, these drugs present high toxicity and uncomfortable collateral effects. In this context, it is necessary the search for new medicines with a high leishmanicidal action and reduced toxicity. An interesting alternative has been the use of drugs that act in the mechanisms of immune response as it has shown promising results. In regard of these drugs, there is the diethyldithiocarbamate,which is a copper-quelating compound that inhibits the function of the superoxide dismutase and it has been demonstrated that this compound increases the production of superoxide and decrease the parasitic load in the experimental cutaneous leishmaniosis. Another alternative drug is the hydroxylamine that reacts with the superoxide and during the methabolism promoves the increase of nitrite peroxide, a molecule capable of destroying intracelular parasites. OBJECTIVE: That being said, this study objetive was to test the in vitro action of the association of Hydroxylamine and DETC against Leishmania braziliensis, amazonensis e infantum. MATERIALS E METHODS: It has been performed toxicity tests in Leishmania braziliensis, amazonensis e infantum and also in murine macrophages derivatived from BALB/C bone marrow. In addition, BALB/C bone marrow-derived macrophages were infected by L. amazonensis, L. braziliensis and L. infantum and treated for 48 hours to assess the percentage of infection and number of amastigotes by counting under a fluorescence microscope. RESULTS: Our results showed a reduction in the growth and viability of the parasites when treated from 2 µM onwards of DETC and at the highest concentration of hydroxylamine (5 mM). Inhibition index of 50% was 33.03 µM to hydroxylamine, 0.247 µM to DETC and 1.676 µM to the association between them agaisnt the Leishmania braziliensis. Regarding the murine macrophages the inhibition index of 50% was 237.0 µM to hydroxylamine, 11.47 µM to DETC and 67.16 µM to the association between the two drugs (DETC/Hydroxylamine=1:2,5). An antagonistic action was observed against the murine macrophages when using the combined concentration of 20 uM from DETC and 500 uM from hydroxylamine. On the other hand, this combined concentrations was highly synergistic to the L. braziliensis. The association between these concentrations was also capable of reducing significantly the infecction percentage and the number of amastigotes per 100 cells. CONCLUSION: Our results demonstrated that the association of hydroxylamine and DETC has powerful antiproliferative effects in promastigotes and amastigotes from L. braziliensis, amazonensis e infantum and presents low toxicity to the murine macrophages.

BANKING MEMBERS:
Presidente - 2236977 - ANTONIO RICARDO KHOURI CUNHA
Externo à Instituição - DIOGO RODRIGO DE MAGALHÃES MOREIRA - Fiocruz-Ba
Interna - 466.269.055-20 - PATRICIA SAMPAIO TAVARES VERAS - Fiocruz - RJ