Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
Division of Pathological Science, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan,
Pharmacology. 2021;106(5-6):294-304. doi: 10.1159/000513034. Epub 2021 Mar 18.
Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects.
The present study investigated the effects of febuxostat on periodontitis in a rat model.
Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined.
In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations.
Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.
牙周炎是一种与生活方式相关的疾病，其特征是牙龈组织的慢性炎症。黄嘌呤氧化酶抑制剂非布司他具有抗炎和抗氧化作用。
本研究旨在探讨非布司他对大鼠牙周炎模型的作用。
雄性 Wistar 大鼠分为 3 组：对照组、牙周炎组和非布司他治疗牙周炎组。通过在上颌第二磨牙周围放置结扎线并给予非布司他（5mg/kg/天）来诱导牙周炎。4 周后，通过微计算机断层扫描和亚甲蓝染色评估牙槽骨丧失。通过定量 RT-PCR 和免疫染色检测骨保护素（OPG）的表达，OPG 是一种骨吸收抑制剂，并通过抗酒石酸酸性磷酸酶染色评估牙龈组织中破骨细胞的数量。通过定量 RT-PCR 和免疫染色测量牙龈组织中促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的 mRNA 和蛋白表达水平。通过 4-羟基-2-壬烯醛（4-HNE）和 8-羟基-2-脱氧鸟苷（8-OHdG）的表达评估牙龈组织中的氧化应激。为了阐明牙周炎的全身影响，检查了血压和葡萄糖耐量。
在牙周炎大鼠中，牙槽骨吸收与 OPG 减少和破骨细胞数量增加有关。TNF-α、IL-1β、4-HNE 和 8-OHdG 在牙周炎大鼠中的牙龈表达上调。非布司他可显著减轻牙槽骨丢失、促炎细胞因子水平和氧化应激。它还减轻了牙周炎引起的葡萄糖不耐受和血压升高。
非布司他通过抑制促炎介质和氧化应激来预防牙周炎及其相关的全身影响。
