Effects of melatonin in the insulin signaling and inflammatory pathway of rats with apical periodontitis

• Grant number: 18/23346-3
• Support type: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2019
• Effective date (End): February 29, 2020
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal researcher: Doris Hissako Matsushita
• Grantee: Bruna Soares Tavares
• Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The relationship between oral inflammatory processes and systemic health has become an aspect of great interest in the medical and dental community, since the number of publications on this topic has increased considerably in recent years. Apical periodontitis (PEA) is an oral inflammation associated with an increase in proinflammatory cytokines that can act locally and systemically. In addition, it has associations with other diseases, such as the metabolic syndrome and Diabetes mellitus. Results from our laboratory demonstrated that PEA in rats causes insulin resistance and changes in the insulin signal. It is known that melatonin (MEL) improves insulin resistance. In this sense, we hypothesized that the administration of MEL in rats with PEA can prevent or decrease the insulin resistance found in these animals. Considering the regulatory effects of MEL on inflammatory processes, it is relevant to evaluate the influence of the administration of MEL on a localized inflammatory process such as PEA. Therefore, the present study aims to verify the effects of MEL administration on insulin resistance, insulin and inflammatory pathways, plasma concentrations of proinflammatory cytokines and lipid profile in rats with PEA. For this, 72 Wistar rats with 60 days of age will be randomly distributed in 4 groups (n = 18): a) control (CN); b) control supplemented with MEL (CNMEL); c) PEA; d) PEA supplemented with MEL (PEAMEL). The PEA will be induced at 60 days of age using a carbon steel drill with a ball at the end with 0.1 mm in the first and second upper and lower right molars. After the induction of PEA, administration with MEL (5 mg/kg) orally (diluted in drinking water) for 60 days will be initiated. At the end of the treatment, the following parameters will be analyzed: 1) tyrosine phosphorylation degree of pp185 and degree of Akt serine phosphorylation (before and after insulin stimulation) in soleus muscle (SOL), extensor digitorum longus muscle (EDL), periepididimal white adipose tissue (WAT) and liver (L); 2) degree of phosphorylation of JNK and IKK±/² in SOL, EDL, WAT and L; 3) plasma concentration of proinflammatory cytokines (TNF-±, IL6, IL10 and IL1²); 4) glycemia; 5) insulinemia; 6) insulin resistance (HOMA-IR); 7) lipid profile (cholesterolemia and triacylglyceridemia). Statistical analysis will be performed by analysis of variance (ANOVA) of two factors followed by the Bonferroni test and differences between groups will be considered significant when p <0.05. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAVARES, B. S.; TSOSURA, T. V. S.; MATTERA, M. S. L. C.; SANTELLI, J. O.; BELARDI, B. E.; CHIBA, F. Y.; CINTRA, L. T. A.; SILVA, C. C.; MATSUSHITA, D. H. Effects of melatonin on insulin signaling and inflammatory pathways of rats with apical periodontitis. International Endodontic Journal, JAN 2021. Web of Science Citations: 0.