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Effect of hyperlipidic diet and melatonin on periapical lesion on insulin sensitivity, inflammation, lipid profile and oxidative stress in skeletal muscle of rats

Grant number: 19/08520-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2022
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Doris Hissako Sumida
Grantee:Rodrigo Martins dos Santos
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Models that simulate diet-related obesity are widely used in animal studies to understand the changes in obesity in humans. Thus, it is essential to verify the relationship between excess weight induced by diets along with associated endodontic infections such as Apical Periodontitis (AP), because both share systemic effects such as insulin resistance and increase of inflammatory mediators. Currently, Melatonin (ME) has been used in clinical scenario for several chronic diseases (Diabetes, dyslipidemias, cardiovascular diseases) in addition to oral pathologies; all due to its antioxidant and anti-inflammatory properties. Therefore, the objective of this study is to investigate the effect of the Hyperlipidic Diet (HLD) and Melatonin (ME) underneath AP on insulin sensitivity, inflammation, lipid profile and oxidative stress in skeletal muscle (MG) of rats. Therefore, 80 rats (Wistar, male, 60 days) will be distributed in 8 groups (n =10): 1) control (CN); 2) AP; 3) HLD; 4) DHL+AP (HLDAP); 5) CN+ME (CNME); 6) AP+ME (APME); 7) HLD+ME (HLDME); 8) HLD+PA+ME (HLDAPME). Initially the HLD, HLDAP, HLDME and HLDAPME groups will be fed for 107 days with a diet composed of 45.5% of standard feed + 22.7% of animal fat + 22.7% of vegetable fat + 9% of sucrose; the other groups will receive standard diet. On the 7th day the groups AP, HLDPA, APME and HLDAPME will be submitted to induction of AP and after 70 days they will receive ME (5 mg/kg, diluted in drinking water for 30 days). At the end of the treatment, the following parameters will be evaluated: 1) water intake, food intake and body mass evolution; 2) histology of the jaws; 3) glycemia, insulinemia and HOMA-IR; 4) plasma concentrations of TNF-±, IL-1², IL-6 and LPS; 5) cholesterolemia and triacylglycerol; 6) gene and protein expression of the Toll-like type 4 receptor and intracellular signaling pathway: MyD88, TRIF, IRF-3 and NFkB in MG; 7) oxidative stress by determining the tissue concentration of thiobarbituric acid and superoxide dismutase reactive substances in MG. Statistical analysis will be by analysis of variance ANOVA followed by Tukey test, the level of significance will be 5%. (AU)