Febuxostat Attenuates the Progression of Periodontitis in Rats

Pharmacology. 2021;106(5-6):294-304. doi: 10.1159/000513034. Epub 2021 Mar 18.

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.

Keywords: Alveolar bone; Inflammation; Oxidative stress; Periodontitis; Xanthine oxidase inhibitor.

MeSH terms

  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / drug therapy*
  • Alveolar Bone Loss / etiology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Disease Models, Animal
  • Febuxostat / pharmacology*
  • Febuxostat / therapeutic use
  • Gingiva / metabolism
  • Gingiva / pathology
  • Insulin Resistance
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Ligation / adverse effects
  • Male
  • Osteoclasts / drug effects
  • Osteoprotegerin / metabolism
  • Oxidative Stress / drug effects
  • Periodontitis / drug therapy*
  • Periodontitis / etiology
  • Periodontitis / metabolism*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • X-Ray Microtomography
  • Xanthine Dehydrogenase / drug effects
  • Xanthine Dehydrogenase / genetics

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Blood Glucose
  • IL1B protein, rat
  • Interleukin-1beta
  • Osteoprotegerin
  • Tumor Necrosis Factor-alpha
  • Febuxostat
  • Xanthine Dehydrogenase