Banca de QUALIFICAÇÃO: MAISIE MITCHELE BARBOSA OLIVEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MAISIE MITCHELE BARBOSA OLIVEIRA
DATE: 21/07/2021
TIME: 14:00
LOCAL: Online (Google Meet)
TITLE:

A DEFINIR

KEY WORDS:

 Inflammation, Mucositis, Losartan, Probiotic.

PAGES: 74
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Intestinal mucositis (IM) is a side effect associated with cancer treatment resulting from chemotherapy. The cytotoxicity of IM resulting from the use of 5-fluouroracil (5-FU) promotes  damage to the mucosal epithelial structure and associated gastrointestinal symptoms that induce  the interruption of treatment by the patient. Currently, there is no efficient therapeutic protocol  that improves the symptoms of intestinal mucositis, in this sense, in order to propose  alternatives that aim at the attenuation of probable in patients affected by IM, the aim of this  study was to evaluate the effect of losartan ( LOS) and the protective effect of the probiotic (Pb)  Lactobacillus mucosae CNPC 007 on 5-FU-induced intestinal mucosite in swiss mice. 5-FU  (450 mg/kg, i.p.) was used to induce an intestinal mucositis on the 1st day. Experimental groups  included: Saline Group, 5-FU Group, LOS Group (5, 25 or 50 mg/Kg) and Probiotic Group.  Losartan was administered 30 min before 5-FU and the probiotic was administered within 14  days prior to IM induction. These were euthanized with thiopentals (90 mg/Kg, i.p.) on the 4th  day after induction and blood and intestinal segments were collected for further analysis. Blood  samples were used to count leukocytes and jejunal segments were separated for enzyme  immunoabsorbance assays for cytokine dosage (TNF-α and IL-1β), oxidative stress (MDA and  GSH) and quantitative polymerase chain reactions in time real (qPCR) for the TWEAK, Fn14  and NF-κB p65 genes. Animals with IM without major intestinal damage in the jejunum  portion, observed by shortened villi, loss of crypt architecture and intense inflammatory cell  infiltrate, evaluated by histopathological analysis with scores of 3 (variation 2-3) and  morphometry (p < 0.001 vs saline group). LOS 50 mg / Kg presented the best results for the  initial analyses, this being a dose adopted for the evaluation of the study. Leukopenia and  greater weight loss were observed in animals with MI (Group 5-FU) compared to the saline  group. Treatment of the LOS 50 and Probiotic groups improved the appearance of villi and  crypts (p < 0.01), reversing as histopathological changes (scores 1, variation 1-2) and  morphometry, leukopenia and weight loss (p < 0.05 vs 5-FU group), induced by 5-FU.  Reduction in the levels of tumor necrosis factor (TNF) -α and interleukin (IL) -1β cytokines for  the LOS 50 and Probiotic groups. LOS 50 reduces oxidative stress markers and the expression  of NF-κB genes p65, TWEAK and Fn14 compared to the 5-FU group (p <0.001), showing a  beneficial effect on induced MI in mice. In conclusion, LOS 50 mg / Kg and the probiotic L.  mucosae CNPC 007 enhance the attenuation of IM symptoms, considering that both treatments  improved the IM injury induced by 5-FU, an expression of pro-inflammatory mediators in  segments jejunals marketed. 

BANKING MEMBERS:
Presidente - 1549705 - ADRIANA FERREIRA UCHOA
Externa ao Programa - 2374605 - AURIGENA ANTUNES DE ARAUJO
Interna - 373.201.654-49 - MARIA APARECIDA MEDEIROS MACIEL - UnP