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

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Bruna Soares Tavares
Total Authors: 1
Document type: Master's Dissertation
Press: Araçatuba. 2020-08-17.
Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
Defense date:
Advisor: Doris Hissako Matsushita

The relationship between oral inflammatory processes and systemic health has become an aspect of great interest to the medical and dental community, since the number of publications on this topic has increased considerably in recent years. Apical periodontitis (PEA) is an oral inflammation associated with an increase in proinflammatory cytokines that can act locally and systemically. In addition, it has associations with other diseases, such as metabolic syndrome and Diabetes Mellitus. Studies in our laboratory have shown that PEA in rats causes insulin resistance (IR) and changes in insulin signal. Melatonin (MEL) is known to improve IR. In this sense, we hypothesized that the supplementation of MEL in rats with PEA could prevent or decrease the IR found in these animals. Considering the regulatory effects of MEL on inflammatory processes, it is important to assess the influence of MEL supplementation on a localized inflammatory process such as PEA. Therefore, the present study aimed to verify the effects of MEL supplementation on IR, on the insulin and inflammatory pathways, on the plasma concentrations of inflammatory cytokines and on the lipid profile in rats with PEA. For that, 72 Wistar rats were divided into 4 groups: a) control (CN); b) control supplemented with MEL (CNMEL); c) PEA (PEA); d) PEA supplemented with MEL (PEAMEL). PEA were induced at 60 days of age by dental pulp exposure of the first and second right molars (upper and lower) to the oral environment. After PEA induction, supplementation with MEL (5 mg/kg) orally (diluted in drinking water) for 60 days was initiated. At the end of treatment, the following parameters were analyzed: 1) glycemia; 2) insulinemia; 3) insulin resistance (HOMA-IR); 4) phosphorylation status of pp185 tyrosine and Akt serine in soleus (SM) and extensor digitorum longus (EDL) muscles; 5) phosphorylation status of IKKα/β and JNK in SM and EDL; 6) plasma concentrations of inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10); 7) lipid profile (cholesterolemia and triacylglyceridemia). The statistical analysis were performed by analysis of variance of two or three factors followed by the Bonferroni test. Differences between groups were considered significant when p < 0,05. The results demonstrated that the PEA in rats promoted: 1) IR; 2) dyslipidemia; 3) increased plasma concentrations of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β); 4) increased phosphorylation status of IKKα/β in SM and EDL; 5) decreased concentration of the anti-inflammatory cytokine IL-10; 6) impaired in the insulin signal (phosphorylation status of pp185 tyrosine and Akt serine) in SM. MEL supplementation in rats with PEA improved insulin sensitivity, decreased concentrations of VLDL, TG, TNF-α and IL-1β, increased IL-10 and changed the insulin signal in SM and the phosphorylation status of IKKα/β in SM and EDL. These results demonstrated that MEL is a potent adjuvant treatment to improve insulin sensitivity, dyslipidemia and changes in the insulin signaling and inflammatory pathways promoted by PEA. In addition, the impact of PEA on general health has also been demonstrated. (AU)

FAPESP's process: 18/23346-3 - Effects of melatonin in the insulin signaling and inflammatory pathway of rats with apical periodontitis
Grantee:Bruna Soares Tavares
Support type: Scholarships in Brazil - Master