Febuxostat Attenuates the Progression of Periodontitis in Rats
Naseratun Nessa, Miyuki Kobara, Hiroe Toba, Tetsuya Adachi, Toshiro Yamamoto, Narisato Kanamura, Giuseppe Pezzotti, Tetsuo Nakata
Abstract
INTRODUCTION: 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. OBJECTIVE: The present study investigated the effects of febuxostat on periodontitis in a rat model. METHODS: 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. RESULTS: 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. CONCLUSION: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.