Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature-Induced Periodontitis

Author(s)

Branco-de-Almeida, Luciana S. ^[1] ; Franco, Gilson C. ^[2] ; Castro, Myrella L. ^[1] ; dos Santos, Juliana G. ^[2] ; Anbinder, Ana Lia ^[3] ; Cortelli, Sheila C. ^[2] ; Kajiya, Mikihito ^{[4, 5]} ; Kawai, Toshihisa ^{[4, 5]} ; Rosalen, Pedro L. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Physiol Sci, BR-13414903 Piracicaba, SP - Brazil

^[2] Univ Taubate, Dept Oral Biol, Sao Paulo - Brazil

^[3] Univ Estadual Paulista UNESP, Sch Dent Sao Jose dos Campos, Dept Biosci & Oral Diag, Sao Paulo - Brazil

^[4] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 - USA

^[5] Forsyth Inst, Dept Immunol, Cambridge, MA - USA

• Document type: Journal article
• Source: Journal of Periodontology; v. 83, n. 5, p. 664-671, MAY 2012.
• Web of Science Citations: 41

Abstract

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. (AU)

• FAPESP's process: 08/00566-6 - In vivo evaluation of the activity of fluoxetine and desipramine in host response in periodontal disease
• Grantee: Luciana Salles Branco de Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate