Evaluation of mandibular bone tissue, insulin resistance and inflammatory cytokins in pinealectomized rats with periodontal disease treated with melatonin

• Grant number: 19/19763-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2019
• Effective date (End): October 31, 2021
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Nayara Gabriely Dourado
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Periodontal disease (PD) is a chronic inflammation that compromises the integrity of tooth support tissues and is associated with increased plasma concentrations of inflammatory cytokines such as tumor necrosis factor alpha (TNF-±) and interleukin-6 (IL-6). These cytokines are related to insulin resistance and increased expression of osteoclasts, which promote increased alveolar bone resorption. In addition, lack of melatonin (MEL) may also contribute to greater bone resorption. Studies have shown that MEL plays an important role in carbohydrate metabolism and has anti-resorptive effects on bone associated with experimentally induced periapical lesions in rats through its anti-inflammatory activity. However, the literature is scarce in relation to studies that investigated the effects of MEL supplementation on insulin sensitivity and alveolar bone resorption in pinealectomized rats with PD. Therefore, the objectives of the present study will be to evaluate in pinealectomized adult rats with PD submitted to MEL replacement: 1) blood glucose; 2) insulinemia; 3) insulin sensitivity; 4) plasma concentrations of inflammatory cytokines; 4) histomorphometry of the region affected by PD. Eighty Wistar rats (40 days old) will be randomly distributed in 8 groups (n = 10 / group) 1) control (CN); 2) pinealectomized (PNX); 3) with periodontal disease (PD); 4) pinealectomized and with periodontal disease (PNXPD); 5) supplemented MEL control (CNMEL); 6) supplemented pinealectomized MEL (PNXMEL); 7) with periodontal disease supplemented MEL (PDMEL); 8) pinealectomized and with periodontal disease supplemented with MEL (PNXPDMEL). Initially the PNX groups were submitted to pinealectomy surgery at 40 days of age and at 60 days of age the animals were submitted to the induction of PD in the lower first molars. Immediately after induction of PD, treatment with MEL (5 mg/kg) was initiated orally (diluted in drinking water) for 28 days. At the end of treatment, the following parameters will be analyzed: 1) water and food intake; 2) evolution of body mass; 3) glucose by the glucose oxidase method; 4) insulinemia by ELISA method; 5) insulin sensitivity by calculating the HOMA-IR index; 6) plasma concentrations of inflammatory cytokines (TNF-alpha and IL-6) by ELISA method; 6) histomorphometry of the region damaged by PD by scanning in the 3D microtomograph (Micro-CT). Statistical analyzes will be performed by ANOVA Three-way analysis of variance, followed by Tukey test and the significance level adopted will be 5% (alpha = 5%).