Protective Mechanisms of Simvastatin in Experimental Periodontal Disease

• Published in: Journal of periodontology (1970) 2013-08, Vol.84 (8), p.1145-1157
• Main Authors: Dalcico, Roberta, de Menezes, Adriana M. A., Deocleciano, Otacilio B., Oriá, Reinaldo B., Vale, Mariana L., Ribeiro, Ronaldo A., Brito, Gerly A. de C.
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - drug effects; Alkaline Phosphatase - drug effects; Alveolar bone loss; Alveolar Bone Loss - prevention & control; Animals; Anti-Inflammatory Agents - therapeutic use; Antioxidants - therapeutic use; Aspartate Aminotransferases - drug effects; Bone Morphogenetic Protein 2 - drug effects; Dentistry; Female; Gingiva - drug effects; Glutathione - drug effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; hydroxymethylglutaryl‐CoA reductase inhibitors; inflammation; Interleukin-10 - analysis; Interleukin-1beta - drug effects; Malondialdehyde - analysis; Matrix Metalloproteinase 1 - drug effects; Matrix Metalloproteinase 8 - drug effects; Nitrates - analysis; Nitric Oxide Synthase Type II - drug effects; Nitrites - analysis; Osteoprotegerin - drug effects; Oxidative Stress - drug effects; periodontitis; Periodontitis - prevention & control; Peroxidase - drug effects; RANK Ligand - drug effects; Rats; Rats, Wistar; Receptor Activator of Nuclear Factor-kappa B - drug effects; Simvastatin - therapeutic use; Tumor Necrosis Factor-alpha - drug effects
• ISSN: 0022-3492; 1943-3670
• DOI: 10.1902/jop.2012.120114

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. Conclusion: The present data suggest that simvastatin prevents inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti‐inflammatory and antioxidant properties.