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Evaluation of the melanin effects on insulin signaling pathway and inflammatory in rats with apical periodontitis submitted to passive inhalation of tobacco

Grant number: 23/12488-0
Support Opportunities:Scholarships in Brazil - Support Program for Fixating Young Doctors
Effective date (Start): September 01, 2023
Effective date (End): August 31, 2024
Field of knowledge:Health Sciences - Dentistry - Endodontics
Acordo de Cooperação: CNPq
Principal Investigator:Doris Hissako Matsushita
Grantee:Maria Sara de Lima Coutinho Mattera
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated research grant:23/01400-4 - Evaluation of the melanin effects on insulin signaling pathway and inflammatory in rats with Apical Periodontitis submitted to passive inhalation of tobacco, AP.R


The association between oral inflammation and systemic health has become a subject of great interest to the medical and dental community, as the number of publications on this topic has increased considerably in recent years. Apical periodontitis (PEA) is related to the increase of proinflammatory cytokines that may act locally and systemically. In addition, this oral inflammation is associated with metabolic syndrome and diabetes mellitus. Previous studies have found that adult rats with PEA have insulin resistance (IR) and alterations in the insulin and inflammatory signal pathways in skeletal muscle. Melatonin (MEL) is known to improve IR and has anti-inflammatory properties. In this sense, we hypothesized that the administration of MEL in rats with PEA may prevent or decrease IR and the alterations in these pathways mentioned above. Therefore, the present study aims to verify the effects of MEL administration on IR, plasma concentrations of inflammatory cytokines, lipid profile and insulin and inflammatory pathways in rats with PEA. For this purpose, 72 (60-day-old) Wistar rats will be randomly assigned to 4 groups (n = 18): a) control (CN); b) control supplemented with MEL (CNMEL); c) rats with induced first and second molars (upper and lower) PEA on the right side (PEA); d) PEA supplemented with MEL (PEAMEL). The PEAs will be induced at 60 days of age by using a surgical round bur measuring 0.1 mm in diameter on the first and second upper and lower molars on the right side. Following PEA induction, the administration of MEL (5 mg/kg) orally through gavage for 60 days will begin. At the end of treatment the following parameters will be analyzed: 1) bone resorption and intensity of inflammatory infiltrate of the right hemimaxyls and hemimandibles; 2) glycemia; 3) insulinemia; 4) insulin resistance (HOMA-IR); 5) plasma concentrations of inflammatory cytokines (TNF-alpha, IL-6, IL-10 and IL-1beta) and melatonin; 6) lipid profile (cholesterolemia and triglyceridemia); 7) pp185 tyrosine and Akt serine phosphorylation status (before and after insulin stimulation) in soleus muscle (MS) and long digital extensor muscle (EDL); 8) GLUT4 glucose transporter protein content in MS and EDL; 9) IKK, JNK, ERK 1/2, NF-²B p65 and NF-²B p50 phosphorylation status in MS and EDL; 10) gene expression of GLUT4 and IRS-1 in MS and EDL. Statistical analysis will be done by two-way analysis of variance (ANOVA) followed by Bonferroni test and differences between groups will be considered significant when p<0.05.

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