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

• Grant number: 23/01400-4
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2023 - June 30, 2025
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Convênio/Acordo: CNPq
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Doris Hissako Matsushita
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated research grant: 22/04868-4 - Effect of melatonin on insulin sensitivity, oxidative stress, and insulin and inflammatory signaling pathways in rats with apical periodontitis submitted to passive inhalation of tobacco, AP.R

Abstract

Apical periodontitis (AP) and smoking may be associated with metabolic syndrome, diabetes mellitus and insulin resistance (IR). Melatonin (MEL) is a hormone with antioxidant and anti-inflammatory properties and with participation in bone remodeling. Previous studies show that MEL improves insulin sensitivity and insulin signaling skeletal muscle of rats with AP. In this context, we hypothesize that metabolic changes in rats with AP are more pronounced with passive inhalation of tobacco and the administration of MEL may prevent or decrease IR. The aims of this work will be to evaluate bone resorption, intensity of inflammatory infiltrate in periapical lesions, insulin sensitivity plasma concentrations of pro-inflammatory cytokines, oxidative stress, insulin and inflammatory signaling pathways in skeletal muscle of adultrats with AP submitted to passive inhalation of tobacco. Therefore, 128 Wistar rats with 60 days of age will be used, distributed into 8 groups: control (C); smoking rats (T); rats with AP (AP); smoking rats with AP (T+AP); control using MEL (CN+MEL); smoking rats using MEL (T+MEL); rats with AP with the use of MEL (AP+MEL); smoking rats with AP using MEL (T+AP+MEL). The smoking groups will receive passive inhalation of cigarettes for 50 days, and on the 20th day, the AP groups will be subjected to induction of apical periodontitis, with the aid of a carbon steel drill in first and second upper and lower molars on the right side. Furthermore, the animals of the MEL groups will be supplemented with melatonin (5 mg/kg, orally by gavage) on the 20th day until the 50th experimental day. At the end of the treatment, the following will be analyzed: a) immunohistochemical analysis of periapical lesions (OPG and RANKL); b) phosphorylation of ERK1/2, NFkB p50, NFkB p65 proteins and their total contents in gastrocnemius skeletal muscle (MG) by the Western blotting (WB) technique; c) content of A kinase 1 associated with the interleukin-1 receptor (IRAK), tumor necrosis factor receptor associated factor 6 (TRAF6) and TNF-± in skeletal muscle tissue (by the WB technique) in MG; d) the degree of serine phosphorylation of Akt in MG, before and after insulin stimulation. (AU)