title: Protective mechanisms of simvastatin in experimental periodontal disease.
abstract: BACKGROUND
  Simvastatin is a cholesterol-lowering drug whose pleiotropic effects may have a therapeutic impact on bone. This study evaluates the effect of simvastatin on rats subjected to experimental periodontal disease.
  
  
  METHODS
  Periodontitis was induced by ligature placement around the maxillary left second molar of rats for 11 days. Groups of six animals received oral saline or simvastatin (3, 10, and 30 mg/kg/day) until sacrifice on day 11. Alveolar bone loss was determined by macroscopic and histologic examination. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total alkaline phosphatase (TAP) were evaluated. Gingival myeloperoxidase activity and gingival levels of interleukin-1β (IL-1β), tumor necrosis factor-α, IL-10, reduced glutathione, malonaldehyde, and nitrate/nitrite were analyzed to investigate oxidative stress and inflammation. Expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinases 1 and 8 (MMP-1 and -8), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were also investigated by immunohistochemistry to assess bone turnover and metabolism. Immunofluorescence microscopy was used to confirm the expression of RANKL in rats' maxillae.
  
  
  RESULTS
  Treatment with simvastatin improved alveolar bone loss within all of the parameters studied, thus demonstrating anti-inflammatory and antioxidant activity. Simvastatin reduced expression of iNOS, MMP-1 and -8, RANK, and RANKL and increased BMP-2 and OPG levels in the periodontal tissue. Simvastatin (30 mg/kg) increased TAP activity on day 11 compared with the saline group. No differences were found in the levels of AST and ALT in any of the groups studied.
  
  
  CONCLUSIONS
  The present data suggest that simvastatin prevents inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory and antioxidant properties.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Dalcico
authors.forename: Adriana M A
authors.initials: AM
authors.lastname: de Menezes
authors.forename: Otacilio B
authors.initials: OB
authors.lastname: Deocleciano
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Vale
authors.forename: Ronaldo A
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Gerly A de C
authors.initials: GA
authors.lastname: Brito
mesh_terms: D000410:Alanine Transaminase / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000187:drug effects; D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000187:drug effects; D005260:Female; D005881:Gingiva / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects; D009566:Nitrates / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D009573:Nitrites / Q000032:analysis; D053244:Osteoprotegerin / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010518:Periodontitis / Q000517:prevention & control*; D009195:Peroxidase / Q000187:drug effects; D053245:RANK Ligand / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000187:drug effects; D019821:Simvastatin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D009566:Nitrates; D009573:Nitrites; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C506032:Tnfrsf11b protein, rat; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde; D019821:Simvastatin; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D020784:Matrix Metalloproteinase 8; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1; D005978:Glutathione