Banca de DEFESA: JULIANA FERREIRA DOS SANTOS BRITO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : JULIANA FERREIRA DOS SANTOS BRITO
DATE: 27/02/2025
TIME: 09:00
LOCAL: on line
TITLE:

Effect of Ezetimibe on cholesterol absorption through the Niemann Pick transporter as a tick control tool

KEY WORDS:

embryonic cells, transporter, lipid, cell viability, molecular modeling

PAGES: 72
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

The use of chemical acaricides is the main method used to control tick infestations. However, a lack of knowledge or even incorrect use of these products leads to a tick population that is more resistant to acaricides, in addition to the environmental impact caused by these chemicals. Therefore, it is important to understand all the biological aspects of ticks to develop new control tools. There is much information about the lipid profile of other arthropods, but little is known about this profile in ticks. Ezetimibe is a drug widely used in the treatment of hypercholesterolemia that acts as a selective inhibitor of cholesterol absorption, impairing its transport. This study aimed to evaluate the viability and lipid profiles of embryonic cell lines of two tick species before and after ezetimibe treatment. To evaluate, through molecular modeling, the interaction of ezetimibe with the cholesterol transporter Niemann Pick of the two species. The cells used were BMP36 and IDE8 from Rhipicephalus (Boophilus) microplus and Ixodes scapularis, respectively. The 12-well plates containing target cells had a predefined concentration. After the formation of a confluent monolayer, the cells were treated with ezetimibe at three different concentrations (25, 50, and 100 μM) and evaluated at three different contact times (24, 48, and 72 h). Viability assays were performed, and the samples were subjected to lipid extraction and analysis by thin-layer chromatography. At 24 h, a decrease in the viability of the IDE8 lineage was observed only at the highest concentration; however, at 48 h, the concentration of 50 μM also showed a significant decrease. In the BMEP36 line, a significant decrease was observed only after 72 h of treatment at 100 µM. The lipid profile of the cell lines was determined, and the presence of cholesterol (CHO) and cholesterol esters (CHOE) was observed. It was observed that tick embryonic cells were influenced by the addition of the cholesterol inhibitor, and the levels of cholesterol and cholesterol ester were reduced. Evaluating the results, it was concluded that the lipid profile found in embryonic cells of different tick lineages was similar to that found in the tick fat body. Therefore, ezetimibe, a substance used to inhibit cholesterol absorption in humans, inhibits cholesterol absorption and affects cholesterol ester levels in tick cells in vitro. Finally, a theoretical molecular docking study was performed using the ChemScore scoring function to observe the interaction of ezetimibe with cholesterol transporter models of both ticks constructed from the human Niemann-Pick C1 protein (NPC1L1) template. It was found that the ligand interacts favorably with the protein present in the cholesterol metabolism of ticks, with a slight advantage in the interaction with the I. scapularis model. However, studies of the energy involved in the formation of these complexes can provide more complete data.

COMMITTEE MEMBERS:
Presidente - 1555317 - EMERSON GUEDES PONTES
Interna - 1979542 - RENATA BARBOSA LACERDA
Externa ao Programa - 1681790 - CRISTIANE MARTINS CARDOSO DE SALLES - UFRRJExterno à Instituição - LUCIANO APARECIDO MEIRELES GRILLO - UFAL
Externo à Instituição - Petter Franco Entringer - UFRJ