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

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 (Ca(2+)), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1beta, 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-1beta and prostaglandin E(2) production.

• Authors: P O Nassar, C A Nassar, M R Guimarães, S G Aquino, D C Andia, M N Muscara, D M P Spolidorio, C Rossa Jr, L C Spolidorio
• Journal: Journal of periodontal research (J Periodontal Res) Vol. 44 Issue 4 Pg. 479-88 (Aug 2009) ISSN: 1600-0765 [Electronic] United States
• PMID: 19076990 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Immunosuppressive Agents
• Interleukin-1beta
• Phosphorus
• Cyclosporine
• Simvastatin
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Alkaline Phosphatase
• Dinoprostone
• Calcium

Topics

• Alkaline Phosphatase (blood)
• Alveolar Bone Loss (chemically induced, physiopathology)
• Alveolar Process (drug effects, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bone Density (drug effects)
• Calcium (blood)
• Cell Count
• Cyclosporine (adverse effects)
• Dinoprostone (analysis)
• Down-Regulation
• Gingiva (drug effects, pathology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Immunosuppressive Agents (adverse effects)
• Interleukin-1beta (analysis)
• Male
• Mouth Mucosa (drug effects, pathology)
• Nitric Oxide Synthase Type II (analysis)
• Osteoblasts (drug effects, pathology)
• Osteoclasts (drug effects, pathology)
• Phosphorus (blood)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Simvastatin (pharmacology)