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The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70\u2009days, the ME groups were treated for 30\u2009days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and interleukin\u20106 were analysed in plasma using biochemical tests and enzyme\u2010linked immunosorbent assay. Thiobarbituric acid\u2010reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF\u2010\u03b1, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF\u2010\u03b1. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non\u2010enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.13852","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T02:03:35Z","timestamp":1666231415000},"page":"164-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Melatonin decreases plasma <scp>TNF<\/scp>\u2010\u03b1 and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high\u2010fat diet"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5122-275X","authenticated-orcid":false,"given":"Rodrigo Martins","family":"dos Santos","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba Brazil"},{"name":"Programa deP\u00f3s\u2010Gradua\u00e7\u00e3o Multic\u00eantrico em Ci\u00eancias 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