Banca de QUALIFICAÇÃO: RENATA CAROLINE COSTA DE FREITAS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : RENATA CAROLINE COSTA DE FREITAS
DATA : 16/12/2016
HORA: 09:00
LOCAL: SALA DE AULA II DO PPGCF
TÍTULO:

miR-26 a and  miR-15b  expression  profiles  as  a  potential  early  biomarker  for  clopidogrel-induced  hepatotoxicity. 

PALAVRAS-CHAVES:

Clopidogrel, Hepatotoxicity, Biomarkers, HepG2

PÁGINAS: 62
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Antiplatelet therapy, especially clopidogrel, is essential for prevention of thrombosis and atherosclerosis. Among clopidogrel adverse effects, the hepatotoxicity is a potential adverse effect related to liver damage. In a scenario of lack of early diagnostic for clopidogrel-induced hepatoxicity, new exosomes-derived miRNAs may be useful for improve the safety of this antiplatelet. Therefore, the miR-26a-5p, miR-145-5p, miR-15b-5p and miR-4701-3p in exosomes were evaluated in vitro aiming use then as potential biomarkers of clopidogrel-induced hepatotoxicity. HepG2 cells were cultured in RPMI containing 5% Exosome-Depleted Fetal Bovine Serum and supplemented with penicillin (10.000 UI/mL), streptomycin (10.000 UI/mL), and sodium bicarbonate (44 mmols/L) at 37°C in 5% CO2 air. Clopidogrel treatments were performed during 24 and 48 h using the concentrations of 6.25, 12.5, 25, 50, and 100 μM. The cytotoxicity was evaluated by flow cytometry to analyze DNA fragmentation and cell cycle. Relative expression of exosomes-derived miRNAs was evaluated by RT-qPCR. Our results revealed that in both periods of treatment the concentrations of 6.25 e 12.5 μM had similar profile that those observed in the control. In relation to the concentrations 25, 50, and 100 μM, it was observed a dose-dependent increase in DNA fragmentation. The miR-26a-5p was upregulated in concentration of 100 μM of clopidogrel and miR-15b-5p were downregulated in this toxic concentration. Therefore, the increased apoptosis in high clopidogrel concentration associated with miR-26a-5p upregulation and miR-15b downregulation are suggestive that these miRNAs profiles may be useful as an innovative diagnostic tool for early detection of clopidogrel-induced hepatotoxicity.

MEMBROS DA BANCA:
Presidente - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externo ao Programa - 2275890 - MARCELO DE SOUSA DA SILVA
Externo ao Programa - 1199127 - SILVIA REGINA BATISTUZZO DE MEDEIROS