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Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1β and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet

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Abstract

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-β (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1β (IL-1β) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107 days. On day 7, experimental AP was induced in the AP groups, and after 70 days, MEL (5 mg/kg) was administered to the MEL groups for 30 days. Plasma concentrations of LPS and IL-1β were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1β plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1β and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

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Acknowledgements

This work was supported by the São Paulo Research Foundation, FAPESP (grant Numbers #2019/08520-0). The authors deny any conflicts of interest related to this study.

Funding

This work was supported by the São Paulo Research Foundation, FAPESP (grant Numbers #2019/08520-0). The authors deny any conflicts of interest related to this study.

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Authors and Affiliations

  1. School of Dentistry, Araçatuba Department of Basic Sciences, São Paulo State University (UNESP), R. José Bonifácio, 1193, Araçatuba, 16015-050, Brazil

    Rodrigo Martins dos Santos, Bianca Elvira Belardi, Thais Verônica Saori Tsosura, Maria Sara de Lima Coutinho Mattera, Núbia Ramos Carvalho, Lara Teschi Bravo, Ana Carla Thalez Ywabuchi Nobumoto, Sandra Helena Penha Oliveira & Dóris Hissako Matsushita

  2. Programa de Pós-Graduação Multicêntrico Em Ciências Fisiológicas (PPGMCF), Sociedade Brasileira de Fisiologia (SBFis), School of Dentistry, São Paulo State University (UNESP), Araçatuba, Brazil

    Rodrigo Martins dos Santos, Bianca Elvira Belardi, Thais Verônica Saori Tsosura, Maria Sara de Lima Coutinho Mattera, Núbia Ramos Carvalho, Lara Teschi Bravo, Ana Carla Thalez Ywabuchi Nobumoto, Sandra Helena Penha Oliveira & Dóris Hissako Matsushita

  3. School of Dentistry, Araçatuba Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), Araçatuba, SP, Brazil

    Fernando Yamamoto Chiba, Nathalia Evelyn Silva Machado, Cristiane Cantiga-Silva & Luciano Tavares Angelo Cintra

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  1. Rodrigo Martins dos Santos
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  2. Bianca Elvira Belardi
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Contributions

Conceptualization: Rodrigo Martins dos Santos and Dóris Hissako Matsushita; Methodology: Rodrigo Martins dos Santos, Bianca Elvira Belardi, Thais Verônica Saori Tsosura, Maria Sara de Lima Coutinho Mattera, Nathalia Evelyn Silva Machado, Cristiane Cantiga Silva, Núbia Ramos Carvalho, Lara Teschi Bravo; Formal analysis and investigation: Fernando Yamamoto Chiba, Sandra Helena Penha Oliveira, Luciano Tavares Angelo Cintra and Dóris Hissako Matsushita; Writing—original draft preparation: Rodrigo Martins dos Santos; Writing—review and editing: Fernando Yamamoto Chiba and Dóris Hissako Matsushita; Supervision: Dóris Hissako Matsushita.

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Correspondence to Rodrigo Martins dos Santos.

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dos Santos, R.M., Belardi, B.E., Tsosura, T.V.S. et al. Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1β and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet. Odontology 111, 687–696 (2023). https://doi.org/10.1007/s10266-022-00782-w

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