Background: Apical periodontitis (PEA) is oral inflammation related to the increase of proinflammatory cytokines that may act locally and systemically. PEA in rats has been shown to cause insulin resistance (IR) and impaired insulin signal. Melatonin (MEL) is known to improve IR. We hypothesized that administration of MEL in PEA rats may prevent the IR found in these animals. Therefore, the aim of this study was to verify, in rats with PEA, the effects of MEL on: IR; the insulin and inflammatory pathways; TNF-α levels.

Methodology: Seventy-two Wistar rats (60 days of age) were distributed into: control (CN); CN+MEL (CNMEL); PEA; PEA+MEL (PEAMEL). PEAs were induced in the first and second upper and lower molars of the right side using a surgical drill. Following PEA induction, MEL (5 mg/kg) was administered orally (drinking water) for 60 days. At the end of treatment were analyzed: 1) HOMA-IR; 2) TNF-α levels; 3) phosphorylation status of pp185 tyrosine, Akt serine and IKKα/β in soleus (SM) and extensor digitorum longus (EDL) muscles. Statistical analysis was performed by analysis of variance (ANOVA) followed by Bonferroni test (p<0.05).

Results: HOMA-IR and TNF-α were higher in the PEA group than in the other groups (HOMA-IR: CN: 2.49 ± 0.24; PEA: 3.57 ± 0.24; CNMEL: 2.17 ± 0.13; PEAMEL: 2.57 ± 0.09 - TNF-α: CN: 8.56 ± 0.84; PEA: 13.42 ± 0.86; CNMEL: 9.21 ± 0.83; PEAMEL: 8.62 ± 0.42). The phosphorylation status of pp185 tyrosine and Akt serine was lower in the PEA group compared to the CN group in SM. Administration of MEL in the PEAMEL group increased the phosphorylation of both proteins. No statistical differences in these parameters were observed between the groups in the EDL muscle. Higher IKKα/β phosphorylation was observed in the PEA group compared to the other groups in both tissues.

Conclusions: PEA promoted IR, increased TNF-α levels, impaired insulin signal in SM and inflammatory pathway activation in SM and EDL. Administration of MEL only prevented changes in insulin signal in MS.


D.H. Sumida: None.


Fundação de Amparo a Pesquisa do Estado de São Paulo (2018/23346-3, 2019/18589-7); São Paulo State University

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