Effects of melatonin on insulin signaling and inflammatory pathways of rats with apical periodontitis.

AIM: To verify the effects of melatonin supplementation on insulin sensitivity, plasma concentrations of inflammatory cytokines, insulin signalling and inflammatory pathways in the soleus (SM) and extensor digitorum longus (EDL) muscles of rats with apical periodontitis (AP). METHODOLOGY: Seventy-two Wistar rats were distributed into 4 groups: (a) control (C), (b) control supplemented with melatonin (M), (c) AP (AP), and (d) AP supplemented with melatonin (AP + M). AP was induced by pulp exposure of the maxillary and mandibular right first and second molars to the oral environment. After AP induction, oral supplementation with 5 mg kg-1 melatonin (diluted in drinking water) for 60 days was initiated. At the end of the treatment, the following were analysed: (1) plasma concentrations of insulin and inflammatory cytokines (TNF-α, IL-6, IL-1ß and IL-10) using ELISA kits; (2) glycaemia using enzymatic assay; (3) insulin resistance using homoeostasis model assessment of insulin resistance (HOMA-IR) index; and (4) phosphorylation status of pp185 tyrosine, Akt serine, IKKα/ß, and JNK in SM and EDL using Western blot. Analysis of variance of two or three factors was performed, followed by the Bonferroni test. P values < 0.05 were considered statistically significant. RESULTS: AP promoted insulin resistance, significantly increased (P < 0.05) plasma concentrations of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), significantly decreased (P < 0.05) the concentration of anti-inflammatory cytokine IL-10, impaired insulin signalling in SM, and increased IKKα/ß phosphorylation status in SM and EDL. Melatonin supplementation in rats with AP improved insulin sensitivity, significantly decreased (P < 0.05) TNF-α and IL-1ß, significantly increased (P < 0.05) IL-10 plasma concentrations, and changed the insulin signalling in soleus muscle and IKKα/ß phosphorylation status in SM and EDL muscles. CONCLUSIONS: Melatonin is a potent adjuvant treatment for improving apical periodontitis-associated changes in insulin sensitivity, insulin signalling and inflammatory pathways. In addition, the negative impact of AP on general health was also demonstrated.

Maternal apical periodontitis is associated with insulin resistance in adult offspring.

AIM: To investigate the plasma concentrations of glucose, insulin and tumour necrosis factor-α (TNF-α) of rats with maternal apical periodontitis (AP) and to explore the effect of maternal inflammation on the initial steps of insulin signalling and the inflammatory pathway in the gastrocnemius muscle (GM) and periepididymal white adipose tissue (pWAT) of adult offspring. METHODOLOGY: Fifteen female Wistar rats were distributed into a control group (CN), a group with 1 tooth with AP (1AP) and a group with 4 teeth with AP (4AP). Thirty days following induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, plasma concentrations of glucose, insulin and TNF-α were quantified. Insulin resistance was evaluated by the homoeostasis model assessment of insulin resistance (HOMA-IR) index. Phosphorylation status of pp185 tyrosine, insulin receptor substrate 1 (IRS-1) serine, IκB kinase α/ß (IKKα/ß) and c-Jun N-terminal kinase (JNK) in the GM and pWAT were measured by Western blot. Analysis of variance was performed, followed by the Tukey's post hoc test. P values <0.05 were considered to be statistically significant. RESULTS: Maternal AP promoted insulin resistance, impaired the initial steps of insulin signalling, significantly increased plasma concentrations of insulin (P < 0.001) and TNF-α (P < 0.05), and enhanced IKKα/ß phosphorylation in the GM and pWAT (P < 0.05) of adult offspring. However, maternal AP did not affect fasting glycaemia and JNK phosphorylation in the GM and pWAT of adult offspring. CONCLUSIONS: Maternal AP was associated with insulin resistance in adult offspring through alterations in insulin signalling and inflammation pathways. The study provides information on the impact of maternal AP on the development of metabolic alterations such as insulin resistance in adult offspring and reinforces the importance of preventing maternal AP in order to maintain the general health of offspring.