MELATONIN EFFECT ON INSULIN SENSITIVITY AND INFLAMMATORY SIGNAL IN RATS WITH TRUE ENDO-PERIODONTAL LESION

• Grant number: 25/10826-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: October 31, 2027
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Marco de Luca Monteiro Sturaro
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

It is well established in the literature that chronic oral inflammations, such as Apical Periodontitis (AP) and Periodontal Disease (PD), can lead to systemic disorders. True Endo-Periodontal Lesion (EPL) is an infectious-inflammatory condition resulting from the association of these two diseases. Both AP and PD are associated with increased levels of pro-inflammatory cytokines that activate intracellular pathways related to impaired insulin signaling, consequently leading to insulin resistance. Moreover, melatonin (MEL) is a hormone with well-documented anti-inflammatory properties. Scientific evidence demonstrates that MEL improves insulin sensitivity in rats with either AP or PD. In this context, it becomes essential to investigate whether adult rats with true EPL may also develop systemic alterations similar to those observed in AP or PD individually, and whether the combination of these diseases may cause more severe systemic effects. Additionally, it is necessary to evaluate the potential influence of MEL supplementation on a localized infectious-inflammatory condition such as true EPL. For this purpose, 96 Wistar rats (2 months old) will be randomly assigned to eight groups: (1) control rats (CN); (2) rats with AP (AP); (3) rats with PD (PD); (4) rats with EPL (EPL); (5) CN rats supplemented with MEL (CNM); (6) AP rats supplemented with MEL (APM); (7) PD rats supplemented with MEL (PDM); and (8) EPL rats supplemented with MEL (EPLM). AP will be induced in the right maxillary first molar by exposing the pulp tissue to the oral environment using a carbon steel bur with a 0.1 mm spherical tip. PD will be induced in the right maxillary second molar using a sterile silk ligature. After 30 days of oral inflammation induction (AP, PD, or true EPL), animals in the MEL groups will receive melatonin supplementation (5 mg/kg by gavage) for 60 days. Following this period, the following parameters will be evaluated: (1) blood glucose levels; (2) insulin levels; (3) insulin resistance (HOMA-IR); (4) inflammatory pathway activation; and (5) plasma concentrations of inflammatory cytokines. Statistical analyses will be performed using analysis of variance (ANOVA) followed by Tukey's post hoc test (p<0.05).