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

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Rodrigo Martins dos Santos
Total Authors: 1
Document type: Doctoral Thesis
Press: Araçatuba. 2023-01-17.
Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
Defense date:
Advisor: Dóris Hissako Matsushita; Sandra Helena Penha de Oliveira

Currently in the literature there are several types of diets administered to animals that aim to verify their effects on metabolism and systemic health of animals, in order to understand how these diets can affect human health. Therefore, it is essential to verify the relationship between the consumption of high-fat diets together with associated endodontic infections such as apical periodontitis (AP), since both share systemic effects such as insulin resistance and increased inflammatory mediators. Currently, melatonin (MEL) has been used in clinical scenarios for several chronic diseases (diabetes, dyslipidemia, cardiovascular diseases) in addition to oral pathologies; all this thanks to its antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effects of ME treatment in rats with apical periodontitis (AP) fed a high-fat diet (HFD) on insulin sensitivity, plasma cytokines, protein and gene expression of Toll-like receptor type 4 (TLR-4) and it signaling pathway and oxidative stress in the gastrocnemius muscle (GM). For this purpose, 80 Wistar rats aged 60 days were divided into 8 groups (n=10): 1) control (CN); 2) AP; 3) HFD; 4) HFD+AP; 5) CN+MEL); 6) AP+MEL; 7) HFD+MEL; 8) HFD+AP+MEL. HFD groups were fed a diet consisting of 45.5% standard chow + 22.7% animal fat and vegetable fat + 9% sugar; the other groups received a standard diet. On the 7th day, the groups with BP underwent surgical induction of BP and, 70 days after AP induction, the animals in the melatonin group received MEL (5 mg/Kg) diluted in drinking water for 30 days. At the end of treatment, the following parameters were evaluated: 1) water and food intake and evolution of body mass; 2) Histology of the jaws; 3) glycemia, insulinemia and HOMA-IR; 4) plasma concentrations of TNF-α, IL-1β, IL-6 and LPS; 5) lipid profile; 6) gene and protein expression of TLR4 and its intracellular signaling pathway: MyD88, TRIF, IRF-3 and NFκB in MG; 7) oxidative stress: protein carbonyl (PC) and thiobarbituric acid reactive substances (TBARs), total non-enzymatic antioxidant capacity (FRAP) and concentrations of reduced glutathione (GSH), superoxide disumutase (SOD), Catalase (CAT) and Glutathione peroxidase (GPx). Statistical analysis was performed by analysis of variance ANOVA followed by Tukey's test, the significance level will be 5%. The results of the present study demonstrated that: 1) The groups fed HFD showed a decrease in body mass, lower water and food intake and higher energy intake when compared to the groups fed a standard diet; 2) The HFD and HFDAP groups showed an increase in the absolute weight of the periepididymal adipose tissue (WAT); groups fed with DHL showed a decrease in MG weight; treatment with ME promoted a decrease in WAT weight; 3) The HFD and DHLPA groups showed increased glycemia; the HFDAP group increased insulinemia; AP, HFD and HFDAP showed insulin resistance and treatment with MEL reversed changes in glycemia, insulinemia and insulin resistance 4) Lipid profile: HFD and HFDAP groups showed an increase in LDL and a decrease in HDL, treatment with ME reversed this change; 5) Cytokines: the AP, HFD and HFDAP groups showed an increase in TNF-α, and ME was reversed; treatment with MEL decreased plasma IL-1β levels in the APMEL and HFDMEL groups; there were no changes in plasma IL-6 levels; there was a reduction in the plasma concentration of LPS only in the HFDMEL group; 6) Gene and protein expression: there was an increase in the protein expression of IRF-3 in the AP, HFD and HFDAP groups in MG and the treatment with MEL decreased the protein expression only in the APMEL and HFDMEL groups; 7) There were no changes in TLR4 gene expression and its cell signaling pathway; 8) Oxidative stress: TBARS increased in the AP and HFDPA groups, and MEL reversed only in the HFDAPMEL group; CP increased in all DHL groups and improved in MEL groups; GSH activity decreased in all experimental groups, and MEL increased this parameter only in CNMEL and APME groups; FRAP did not change between groups, but ME treatment increased its activity in APMEL and HFDMEL groups; MEL increased SOD in the CN and AP groups. It is concluded that the association of HFD and AP intensified the alterations observed in this study. ME treatment proved to be an important resource for reversing these changes due to its antioxidant, anti-inflammatory and hypocholesterolemic effects. Therefore, clinical studies must be carried out to verify the systemic and inflammatory effects of AP and HFD. (AU)

FAPESP's process: 19/08520-0 - Effect of hyperlipidic diet and melatonin on periapical lesion on insulin sensitivity, inflammation, lipid profile and oxidative stress in skeletal muscle of rats
Grantee:Rodrigo Martins dos Santos
Support Opportunities: Scholarships in Brazil - Doctorate