AIM: This study aimed to explore the possible bidirectional interrelations between fructose-induced metabolic syndrome (MS) and apical periodontitis (AP). METHODOLOGY: Twenty-eight male Wistar rats were distributed into four groups (n = 7, per group): Control (C), AP, Fructose Consumption (FRUT) and Fructose Consumption and AP (FRUT+AP). The rats in groups C and AP received filtered water, while those in groups FRUT and FRUT+AP received a 20% fructose solution mixed with water to induce MS. The groups AP and FRUT+AP had the pulp of their right mandibular first molar exposed to induce AP. Food consumption, murinometric measurements, blood glucose levels and glucose tolerance were monitored. Fifty-six days after the start of the experiment, the animals were euthanized, and serum samples were collected for metabolomic analysis. Mandibles, livers and right kidneys were also collected. The area and volume of the periapical lesions were calculated using micro-computed tomography. Histopathological evaluation was performed. Kruskal-Wallis followed by the Student-Newman-Keuls or Mann-Whitney tests and one-way anova followed by Tukey's or Independent t-test were used for non-parametric and parametric data, respectively (p <
.05). Multivariate analysis and variable importance in projection score were applied to assess metabolite profile differences among groups (p <
.05). RESULTS: FRUT and FRUT+AP groups showed significantly increased fluid intake, body mass, abdominal circumference, blood glucose levels, liver weight and visceral fat weight (p <
.05), indicating the development of MS. The analyses of the metabolite profile suggest increasing glucose, histidine, lactate, fatty acid and phenylalanine in the FRUT+AP group. There were no significant differences in volume and area of periapical lesions in micro-CT analyses (p = .1048 and p = .7494, respectively). Histopathological analysis of the hemimandibles demonstrated areas of inflammatory response, necrosis and microabscess in the periapical region. Hepatic histopathological observations indicated notable differences in cell appearance, with the FRUT and FRUT+AP groups showing signs of microsteatosis. Kidney analysis revealed Bowman's space dilation in the FRUT and AP groups, while the FRUT+AP group exhibited retracted Bowman's space, suggesting a possible alteration in renal filtration capacity. CONCLUSIONS: MS had no impact on the progression of AP in rats. However, AP exacerbated the systemic state affected by MS, with changes in liver and kidney tissues and metabolite levels.