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| Author(s): |
Sara Lima Anacleto
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2020-02-21 |
| Examining board members: |
Neuza Mariko Aymoto Hassimotto;
William Tadeu Lara Festuccia;
Ronaldo Vagner Thomatieli dos Santos
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| Advisor: | Neuza Mariko Aymoto Hassimotto |
| Abstract | |
Cholesterol is one of the trigger of the oxidative stress in the pancreatic-β cell, generating high level of reactive oxygen species, such as the superoxide anion, which leads to impairment of insulin synthesis and secretion. Currently, the intake of bioactive compounds, such as citrus flavanones, which present anti-inflammatory and antioxidant activities, could reduce oxidative stress in β cells improving its function. Thus, the purpose of this project is evaluating the protection effect of flavanones on pancreatic-β cells under oxidative stress. The phase II metabolites of flavanones evaluated were naringenin 7-O-glucuronide, hesperetin 3\'-O-glucuronide, and hesperetin 7-O-glucuronide and also two catabolites produced from intestinal microbiota, hippuric acid and 3-(4-hydroxyphenyl)propionic acid, major circulating compounds after flavanone naringenin intake. Cells were analyzed for cell viability and modulation of oxidative stress. Initially, conditions of 320 µM cholesterol and 6 h of incubation were standardized for the induction of oxidative stress in the β cells of the Min6 line. The flavanone metabolites did not affect cell viability at concentrations tested (2 µM, 5 µM , 10 µM e 100 µM). Cholesterol significantly reduced the cell viability (by up to 40%) in dose and time-dependent, with significant improvement in the presence of metabolites. Moreover, flavanone metabolites attenuated the oxidative stress by significantly reducing lipid peroxidation, superoxide anion, and hydrogen peroxide. In response to the reduction of reactive oxygen species, a decrease in superoxide dismutase (55% to 82%) and glutathione peroxidase (10% a 53%) activities was observed, which these values are found high with cholesterol. Moreover, mitochondrial function and insulin secretion was improved with treatment with all flavanone metabolites, in addition to a reduction in apoptosis. This way, the improvement in the cellular function of pancreatic-β cells was observed, due to the direct antioxidant action of phase II metabolites and flavanone catabolites, which is reinforced by the fact that they are detected inside the cell, with the exception of 3-(4-hydroxyphenyl) propionic acid, which was not found neither in the middle nor inside of cell. The phase II metabolites were detected after 6 h of incubation, whereas the phenolic acids were not detected, indicating possible absorption by the cells. Thus, these results demonstrated that flavanone metabolites protected pancreatic-β cells against oxidative stress and harmful effects induced by cholesterol, mitigating their effect, acting as direct antioxidant downstream a positive effects observed by the improvement of oxidative stress and pancreatic β-cell function. (AU) | |
| FAPESP's process: | 18/03965-0 - Citrus Flavanones- mechanisms of protection of pancreatic-beta cells under oxidative stress |
| Grantee: | Sara Lima Anacleto |
| Support Opportunities: | Scholarships in Brazil - Master |