Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats

Autor(es)

Nassar, P. O. ^[1] ; Nassar, C. A. ^[2] ; Guimaraes, M. R. ^[1] ; Aquino, S. G. ^[1] ; Andia, D. C. ^[1] ; Muscara, M. N. ^[3] ; Spolidorio, D. M. P. ^[1] ; Rossa, Jr., C. ^[1] ; Spolidorio, L. C. ^[4]

Afiliação do(s) autor(es)

^[1] State Univ Sao Paulo, Dent Sch Araraquara, Dept Periodontol, Araraquara, SP - Brazil

^[2] Univ State W Parana Unioeste, Cascavel Dent Sch, Dept Periodontol, Cascavel, Parana - Brazil

^[3] Univ Sao Paulo USP, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[4] State Univ Sao Paulo UNESP, Dent Sch Araraquara, Dept Physiol & Pathol, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PERIODONTAL RESEARCH; v. 44, n. 4, p. 479-488, AUG 2009.
• Citações Web of Science: 25

Resumo

Background and Objective: Cyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease. Material and Methods: Groups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca(2+)), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1 beta, prostaglandin E(2) and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed. Results: Treatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent. Conclusion: This study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1 beta and prostaglandin E(2) production. (AU)

• Processo FAPESP: 04/09851-4 - Avaliação do efeito da sinvastatina em ratos submetidos à periodontite experimental e imunossuprimidos por ciclosporina-A e tacrolimus
• Beneficiário: Luis Carlos Spolidorio
• Modalidade de apoio: Auxílio à Pesquisa - Regular