Melatonin protects liver and periodontal tissues from inflammation exacerbated by metabolic syndrome–periodontitis association.

Metabolic syndrome (MetS) and periodontal disease (PD) are prevalent inflammatory conditions with global health implications. Their bidirectional interaction amplifies systemic and metabolic inflammation, worsening periodontal destruction while PD exacerbates metabolic disturbances. This study evaluates the combined impact of MetS and PD on periodontal and hepatic health and examines melatonin (MEL) as a therapeutic agent. Male Wistar rats were assigned to Control, MetS, PD, MetS + PD, and MetS + PD+MEL groups. MetS was induced with 10% fructose intake for 35 days and PD by ligature placement for 4 days. MEL (10 mg/kg) was administered to assess its anti-inflammatory effects. Body weight, glycemia, lipid profile, and liver enzymes were measured. Radiographic and histomorphometric analyses were performed on the jaw, and NLRP3 and IL-10 expression assessed by immunohistochemistry in jaw and liver. MetS + PD animals showed aggravated hyperglycemia, dyslipidemia, hepatic injury, and severe periodontal destruction, with increased NLRP3 and reduced IL-10 levels. MEL attenuated these alterations, improving metabolic outcomes, preserving periodontal bone, restoring hepatic histology and enzyme levels, and modulating inflammation by decreasing NLRP3 and increasing IL-10. These findings indicate that MetS and PD synergistically intensify inflammatory and metabolic disturbances, and that MEL counteracts this exacerbated inflammatory burden emerging as a promising adjunct therapeutic candidate for systemic–oral inflammatory conditions.