title: Fluoxetine inhibits inflammatory response and bone loss in a rat model of ligature-induced periodontitis.
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)-1β, 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-1β 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Branco-de-Almeida
authors.forename: Gilson C
authors.initials: GC
authors.lastname: Franco
authors.forename: Myrella L
authors.initials: ML
authors.lastname: Castro
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Dos Santos
authors.forename: Ana Lia
authors.initials: AL
authors.lastname: Anbinder
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Cortelli
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kawai
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Rosalen
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D024022:Fibrillar Collagens / Q000032:analysis; D005473:Fluoxetine / Q000627:therapeutic use*; D005881:Gingiva / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008026:Ligation; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D046509:Tissue Culture Techniques
chemical_list: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D024022:Fibrillar Collagens; D005473:Fluoxetine; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D052247:Nitric Oxide Synthase Type II; D017367:Selective Serotonin Reuptake Inhibitors