Sarmento Estéfano Borgo, Sassone Luciana Moura, Pinto Karem Paula, Ferreira Cláudio Malizia Alves, da Fidalgo Tatiana Kelly Silva, Lopes Ricardo Tadeu, Alves Adriana Terezinha Neves Novellino, Freitas-Fernandes Liana Bastos, Valente Ana Paula, Neves Renata Heisler, da Silva Emmanuel João Nogueira Leal
Department of Integrated Clinical Procedures, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil.
Department of Community and Preventive Dentistry, School of Dentistry, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil.
Int Endod J. 2025 Mar;58(3):467-483. doi: 10.1111/iej.14189. Epub 2025 Jan 11.
This study aimed to explore the possible bidirectional interrelations between fructose-induced metabolic syndrome (MS) and apical periodontitis (AP).
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).
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.
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.
本研究旨在探讨果糖诱导的代谢综合征（MS）与根尖周炎（AP）之间可能存在的双向相互关系。
将28只雄性Wistar大鼠分为四组（每组n = 7）：对照组（C）、AP组、果糖摄入组（FRUT）和果糖摄入加AP组（FRUT+AP）。C组和AP组大鼠饮用过滤水，而FRUT组和FRUT+AP组大鼠饮用与水混合的20%果糖溶液以诱导MS。AP组和FRUT+AP组将其右下颌第一磨牙的牙髓暴露以诱导AP。监测食物摄入量、鼠体测量指标、血糖水平和葡萄糖耐量。实验开始56天后，对动物实施安乐死，并采集血清样本进行代谢组学分析。同时采集下颌骨、肝脏和右肾。使用微型计算机断层扫描计算根尖周病变的面积和体积。进行组织病理学评估。非参数数据分别采用Kruskal-Wallis检验，随后进行Student-Newman-Keuls或Mann-Whitney检验；参数数据采用单因素方差分析，随后进行Tukey检验或独立t检验（p < 0.05）。应用多变量分析和投影变量重要性得分来评估各组之间的代谢物谱差异（p < 0.05）。
FRUT组和FRUT+AP组的液体摄入量、体重、腹围、血糖水平、肝脏重量和内脏脂肪重量显著增加（p < 0.05），表明发生了MS。代谢物谱分析表明，FRUT+AP组的葡萄糖、组氨酸、乳酸、脂肪酸和苯丙氨酸增加。微型计算机断层扫描分析中根尖周病变的体积和面积无显著差异（分别为p = 0.1048和p = 0.7494）。半下颌骨的组织病理学分析显示根尖周区域有炎症反应、坏死和微脓肿区域。肝脏组织病理学观察表明细胞外观存在显著差异，FRUT组和FRUT+AP组有微脂肪变性迹象。肾脏分析显示FRUT组和AP组有鲍曼间隙扩张，而FRUT+AP组表现为鲍曼间隙退缩，提示肾滤过能力可能发生改变。
MS对大鼠AP的进展没有影响。然而，AP加剧了受MS影响的全身状态，导致肝脏和肾脏组织以及代谢物水平发生变化。
