الفهرس 
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Abstract
The purpose of this study was to investigate and evaluate the effect of simvastatin therapy taken orally on CsA induced alveolar bone loss through immunohistochemical detection of BMP2.
Cyclosporin-A- has been used as an immunosuppressant to prevent the rejection of organ transplants. However, alveolar bone loss is an important negative side-effect of this drug.Simvastatin, a hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is known to inhibit cholesterol biosynthesis. It has advanced effects on bone formation in vivo and in vitro.
Twenty-four adult male rats were divided randomly into three groups:
group I : Control (consisting of 4 rats) was injected with 1 ml saline.
group II : Cyclosporin -A- group (consisting of 10 rats), were treated with Cyclosporin -A-, subcutaneous daily injection (10 mg/kg body weight, once a day).
group III : Cyclosporin A/simvastatin group (consisting of 10 rats), this group were treated with both Cyclosporin -A- and Simvastatin. Simvastatin taken by oral daily doses (once a day) at 20 mg/kg.
from each group, 5 rats were sacrificed after 15 and 30 days consecutively after commencement of the daily treatments.
At the end of the experiments, the rats were euthanized. The right mandibles were selected and fixed in 5% nitric acid and 10% neutral formalin for 24 to 30 hours for decalcification then the samples were processed for preparing paraffin sections for light microscopic examination, immunohistochemical examination, and image analysis.
Histological findings revealed that CsA adversely affect alveolar bone structure.The surface of the alveolar bone adjacent to the PDL showed irregular outline of punched out appearance with the presence of osteoclast in Howship‘s lacunae, the numbers of osteoclasts were significantly increase compared to the control.(p=0.019 after 15 days, p= 0.009 after 30 days) But in Simvastatin treated group the number of osteoclast cells was significantly
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decreased than CsA group (p=0.038 after 15 days, p=0.024 after 30 days). In addition, the osteoblast cells in CsA group exhibited less number and size than the control group with discontinuity along the alveolar bone surface. That was significantly decreased than the control (p=0.019 after 15 days, p= 0.001 after 30 days). On the other hand, in Simvastatin group, Osteoblast cells appeared voluminous and overlapped arranged in several rows, as a result of its activity. That showed a statistically significant increase than the CsA group (p =0.005 after 15 days, p <0.001 after 30 days).
The osteocytes appeared as small lacunae with pyknotic nuclei in CsA group, while in Simvastatin group they appeared as a wide lacunae with large nuclei and regularly distributed in the alveolar bone
In CsA the bone trabeculae revealed a lower thickness than in the control group with large bone marrow spaces. There was a statistically significant decrease in bone volume compared to the control (p = 0.002 after 15 days, p<0.001 after 30 days). After Simvastatin therapy, a generalized appearance of restoration of the normal bone architecture was pronounced. The bone tabeculae appeared thicker than CsA treated group with relatively narrow bone marrow spaces. A remarkable difference in histological picture was confirmed by image analysis of the bone volume, that was significantly increased than the CsA group (p <0.001) after 15 and 30 days, and significantly increased than the control group after 30 days (p= 0.040).
The new concept in our study was determining a quantitative expression of BMP-2 protein; the immunostaining optical density (IOD). The image analysis stated a significantly decreased in IOD in CsA group compared to the control after 15 and 30 days (p value <0.001) that was appeared as a weak immunoreactivity for osteoblast and osteoclast cells in CsA. The IOD of Simvastatin group showed a significant increased than the CsA group after 15 and 30 days (p value <0.001). That appeared as a strong immunoreactivity for osteoblast and osteoclast in Simvastatin group.