Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats |
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Authors: | P. O. Nassar,C. A. Nassar,M. R. Guimarã es,S. G. Aquino,D. C. Andia,M. N. Muscara,D. M. P. Spolidorio,C. Rossa Jr,L. C. Spolidorio |
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Affiliation: | Department of Periodontology, Dental School of Araraquara, State University of São Paulo (UNESP), Araraquara, SP, Brazil;, Department of Periodontology, Cascavel Dental School, University of State of West of Parana (Unioeste), Cascavel, Parana, Brazil;, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), SP, Brazil;and Department of Physiology and Pathology, Dental School of Araraquara, State University of São Paulo (UNESP), Araraquara, SP, Brazil |
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Abstract: | 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 (Ca2+), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1β, prostaglandin E2 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-1β and prostaglandin E2 production. |
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Keywords: | simvastatin cyclosporine A alveolar bone loss periodontitis |
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