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Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature-Induced Periodontitis
  • Universidade Estadual de Campinas (UNICAMP)
  • Univ Taubate
  • Universidade Estadual Paulista (UNESP)
  • Forsyth Inst
  • Harvard Univ
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
  • National Institutes of Health/National Institute of Dental and Craniofacial Research
Sponsorship Process Number: 
  • FAPESP: 08/00566-6
  • CAPES: 4073/08-8
  • NIH/NIDCR: DE-018499
  • NIH/NIDCR: DE-019917
Background: Fluoxetine, a selective serotonin reuptake inhibitor, has been found recently to possess anti-inflammatory properties. The present study investigates the effects of fluoxetine on inflammatory tissue destruction in a rat model of ligature-induced periodontal disease.Methods: Thirty male Wistar rats were randomly assigned into three groups (n = 10 animals per group): 1) control rats (without ligature); 2) rats with ligature + placebo (saline; oral gavage); and 3) rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histologic analyses were performed on the furcation region and mesial aspect of mandibular first molars of rats sacrificed at 15 days after ligature-induced periodontal disease. Reverse transcription-polymerase chain reaction and zymography were performed to analyze the mRNA expression of interleukin (IL)-1 beta, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase and the MMP-9 activity, respectively, in gingival tissues samples.Results: Compared to the ligature + placebo group, alveolar bone loss was reduced in the fluoxetine group (P <0.05), and the amount of collagen fibers in the gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after ligature attachment, fluoxetine administration reduced IL-1 beta and COX-2 mRNA expression. Fluoxetine downregulated MMP-9 activity, without affecting MMP-9 mRNA expression induced by ligature, compared to the ligature + placebo group (P <0.05). These data suggest that fluoxetine suppressed proinflammatory responses, as well as proteolytic enzyme activity, induced by ligature.Conclusion: In the present study, fluoxetine suppresses the inflammatory response and protects against periodontal bone resorption and destruction of collagen fibers, suggesting that fluoxetine can constitute a promising therapeutic approach for periodontal diseases. J Periodontol 2012;83:664-671.
Issue Date: 
Journal of Periodontology. Chicago: Amer Acad Periodontology, v. 83, n. 5, p. 664-671, 2012.
Time Duration: 
Amer Acad Periodontology
  • Bone resorption
  • collagen
  • fluoxetine
  • inflammation
  • periodontitis
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Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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