EVALUATION OF CYTOKINES AND INFLAMMATORY MEDIATORS IN THE HIPPOCAMPUS OF RATS WITH APICAL PERIODONTITIS TREATED WITH MELATONIN

• Grant number: 25/04684-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Louise Elias de Carvalho
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Currently, it is well-established in the literature that chronic inflammations in teeth such as Apical Periodontitis (AP) and Periodontal Disease (PD) can cause systemic disorders. AP is an inflammation at the apex of the tooth root, usually caused by bacterial infection originating from the root canal system. The inflammatory response generated by this infection promotes an increase in pro-inflammatory cytokines, especially TNF-¿, and IL-1¿, which can spread systemically. In addition, these cytokines are related to the increased expression of the proteins neuronal proteins, such as tau (TAU) and ¿-amyloid, which are involved in the development of cognitive alterations present in neurodegenerative pathologies such as dementia. Due to all these factors, there is a correlation between inflammation and Alzheimer's. However, literature is scarce in relation to studies that relate AP to systemic cognitive alterations. Furthermore, studies have shown that melatonin (MEL) has anti-inflammatory and antioxidant properties and can reverse systemic changes caused by PD and AP. Therefore, the aim of this study will be to investigate whether young rats will undergo changes in pro-inflammatory cytokines, such as TNF-¿, and IL-1¿ and in the mediators of inflammatory signaling, such as IKK¿/¿ and JNK content in the hippocampus after 90 days of AP induction and whether treatment with MEL can decrease the expression of this cytokine in this brain structure. For this purpose, 32 Wistar rats (2 months) will be distributed into 4 groups: 1) control rats (CN); 2) control rats treated with MEL (CNMEL); 3) rats with 4 APs caused in the 1st and 2nd upper and lower molars on the right side (PA); 4) rats with 4 APs treated with MEL (PAMEL). AP will be induced by exposing the pulp tissue to the oral environment, using a carbon steel bur equipped with a 0.1 mm ball at the end. After 30 days of oral inflammation (AP) induction, treatment with MEL (5 mg/kg, oral gavage) will be initiated for 60 days. After the MEL treatment period, euthanasia will be performed, and the following experiment will be performed: evaluation of the levels of TNF-¿, IL-1¿, and the phosphorylation of IKK¿/¿ and JNK in the hippocampus using the Western blotting technique. (AU)