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

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 in 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 the right hemimaxilla and right hemimandible, 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: bone resorption and intensity of inflammatory infiltrate of the right hemimaxilla and right hemimandible; blood glucose; insulinemia; insulin sensitivity (HOMA-IR); plasma concentrations of pro-inflammatory cytokines (IL-6 and TNF-a); degree of phosphorylation in pp185 tyrosine; inflammatory signaling pathways (degree of phosphorylation of IKKa/b and JNK); oxidative stress (superoxide dismutase - SOD and thiobarbituric acid reactive substances - TBARS) in the gastrocnemius muscle (GM). The normality of the data will be evaluated by the Shapiro-Wilk test. In reference to the normality test results, parametric or nonparametric tests will be used to compare bone resorption, infiltrate intensity inflammatory, glycemia, insulinemia, insulin sensitivity, plasma concentrations of pro-inflammatory cytokines (IL-6 and TNF-±), degree of phosphorylation in pp185 tyrosine, inflammatory signaling pathways (degree of phosphorylation of IKKa/b and JNK) and stress oxidative (superoxide dismutase - SOD and thiobarbituric acid reactive substances - TBARS) in GM between groups. The significance level will be 5%. (AU)