Title : Anti-inflammatory and Anti-oxidative Effects of Febuxostat on Periodontitis Rats Model
Abstract:
Objectives: Periodontal disease is quite prevalent and affects about 20-50% of global population. Periodontitis is a chronic inflammatory disease of the supporting structures of the teeth. When periodontal pathogens enter into the blood stream, such lifestyle diseases develop. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. This study aims to evaluate the effects of febuxostat on periodontitis in a rat model. Methods: Wistar rats were used in this study being divided randomly into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Experimental periodontitis was induced by placing the ligature wire around the upper 2nd molar of the rat; the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was evaluated by micro-computed tomography and methylene blue staining. The expression of bone resorption inhibitor osteoprotegerin (OPG), in gingiva was detected by quantitative RT-PCR and immunological staining. Tartrate-resistant acid phosphatase (TRAP) staining was used to assess the number of osteoclasts in gingival tissue. Quantitative RT-PCR and immunological staining were used to examine the inflammatory cytokines expression. Oxidative stress in gingiva was also evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). In addition, blood pressure and glucose tolerance were examined to clarify the systemic effects of periodontitis.
Results: In rats with periodontitis, alveolar bone resorption increased with reductions in OPG; the number of TRAP positive osteoclasts grew. The expression of TNF-α, IL-1β, and 4-HNE, and 8-OHdG in the gingiva was up-regulated in the periodontitis group and treatment with febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevation.
Conclusions: Febuxostat prevented the progression of periodontitis and associated systemic effects by suppressing proinflammatory mediators and oxidative stress.