Banca de DEFESA: MAYARA SANTA ROSA LIMA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MAYARA SANTA ROSA LIMA
DATE: 28/07/2022
TIME: 08:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/vgd-wqrn-hbe
TITLE:

ANTI-INFLAMMATORY EFFECT OF PEPTIDES AND PROTEINS ON INTEGRITY AND FUNCTIONALITY OF THE INTESTINAL BARRIER

KEY WORDS:

Amino Acids, Peptides, and Proteins. Intestinal Mucosa. Leukocyte Elastase. Systematic Review. Tumor Necrosis Factor-Alpha.

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

A healthy intestinal barrier protects the individual against antigen translocation, ensuring a controlled inflammatory environment. The first two chapters of this thesis refer to a systematic review (SR), which aimed to understand the mechanisms of action of anti-inflammatory molecules that reduce TNF-α and their effects on the intestinal barrier in animal models. The protocol of the first chapter was registered in PROSPERO and guided the elaboration of the RS, presented in the second chapter. The articles were selected according to the PICO strategy (Population, Intervention, Comparison/Control and Outcomes), from PubMed, Scopus, Web of Science, EMBASE and ScienceDirect databases. Twenty-five articles were selected and the risk of bias assessment was performed using the SYRCLE tool. The results show that the anti-inflammatory molecules that acted by reducing TNF-α acted mainly on the TNF-TNFR1/TNFR2 and TLR4/MD2 complex signaling pathways, and consequently on the NF-κB pathway, which reduced the symptoms of inflammatory diseases and the macroscopic, histological and intestinal permeability aspects. In the third chapter, the proposal and methodological validation of an inflammation model with TNF-α in co-culture of Caco-2:HT29-MTX intestinal cells is presented. In the fourth chapter, the trypsin inhibitor isolated from tamarind seeds (TTI) was evaluated in vitro regarding its interaction with bacterial lipopolysaccharide (LPS) and its action against human neutrophil elastase. In addition, the effects on the integrity and functionality of the intestinal barrier in cell culture and in an experimental obesity model were evaluated, including hematological, biochemical and inflammatory parameters. The cell study was performed in differentiated Caco-2:HT29-MTX co-cultures and evaluated cell viability and production of reactive oxygen species during contact of cell monolayers with ITT. In addition, transepithelial electrical resistance and permeability were evaluated in monolayers previously inflamed with TNF-α (50 ng/mL) and treated with TTI (1.0 mg/mL, after or during the inflammatory stimulus). For the animal study, obese Wistar rats (n=15) were divided into three groups: no treatment group (n=5), group treated with a nutritionally adequate diet (n=5) and group treated with TTI (25 mg/ kg/day, n=5) for ten days. TTI did not interact with LPS, but showed inhibition against human neutrophil elastase (93%). In the cell study, ITT did not alter cell viability and did not present pro- or antioxidant properties, as well as it did not prevent damage or restore the monolayers integrity. In the in vivo experiment, TTI-treated rats had significantly lower plasma concentrations of inflammatory cytokines, and of other obesity-related parameters, such as total leukocyte count, fasting glucose, and LDL-c, compared to animals treated with a nutritionally adequate diet. They also showed better histopathological and histomorphometric results in the small intestine, although there were no significant differences between the groups regarding most semiquantitative parameters, intestinal permeability and concentration of inflammatory cytokines in the intestine. Thus, it is concluded that TTI, at the concentrations tested, was safe for cell cultures and reduced systemic inflammation in Wistar rats, which possibly reflected in the improvement of the morphology of the intestinal epithelium in the treated animals. In view of the results, it is believed that TTI has another type of action on the intestinal epithelium, probably related to the inhibitory activity against neutrophil elastase.

COMMITTEE MEMBERS:
Externo à Instituição - FRANCISCO ADELVANE DE PAULO RODRIGUES - IFCE
Presidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externa à Instituição - ANA VLADIA BANDEIRA MOREIRA - UFJF
Externa ao Programa - 2646462 - BRUNA LEAL LIMA MACIEL - nullExterna ao Programa - 2865332 - DALINE FERNANDES DE SOUZA ARAUJO - nullExterna ao Programa - 1971809 - JULIANA KELLY DA SILVA MAIA - null