Abstract
The aim of this study is to determine the effects of Atorvastatin treatment, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, in periodontal disease. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1) non-ligated treatment (NL), (2) ligature only (L), (3) ligature plus 1 mg/kg Atorvastatin daily for 10 days, (4) ligature plus 5 mg/kg Atorvastatin daily for 10 days, and (5) ligature plus 10 mg/kg Atorvastatin daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by Measurement of alveolar bone loss, Histopathology and immunohistochemistry to determine of the expression of COX-2, MMP-2, MMP9, and RANKL/RANK/OPG. ELISA assay was used to quantitate the levels of IL-1β, IL-10, TNF-α, myeloperoxidase, malondialdehyde, and glutathione. The periodontal group treated with 10 mg/kg of Atorvastatin (3.9±0.9 mm; p<0.05) showed reverse the alveolar bone loss caused Experimental Periodontal Disease compared to (L) (7.02±0.17 mm). The periodontal group treated with 10 mg/kg of Atorvastatin showed a significant reduction in MPO and MDA (p<0.05) compared to ligature only group (L). Similarly in this group, the levels of the proinflammatory cytokines IL-1β and TNF-α were significantly decreased (p<0.05). Furthermore, MMP-2, MMP-9, RANKL/RANK, and COX-2 were all downregulated by Atorvastatin treatment, while OPG expression was increased. The findings support a role of Atorvastatin for reducing the bone loss, inflammatory response, oxidative stress, and expression of extracellular matrix proteins, while reducing RANK/RANKL and increase OPG in periodontal disease.
Highlights
Atorvastatin is a member of the statin class of inhibitors
The animals were assigned randomly to the following five groups (10 animal for group): (1) a non-ligated group that received Water (NL), (2) a ligated group that received Water (L), (3) a ligated group treated with 1 mg/kg Atorvastatin (1 mg/kg Atorvast), (4) a ligated group a group treated with 5 mg/kg Atorvastatin (5 mg/kg Atorvast), and (5) a ligated group a group treated with 10 mg/kg Atorvastatin (10 mg/kg Atorvast)
Rats with experimental periodontitis (EPD) (L) showed a significant alveolar bone loss compared to non-ligated treatment (NL) (NL = 1.460.07 mm; L = 7.0260.17 mm; p,0.001)
Summary
Atorvastatin is a member of the statin class of inhibitors. Statins are responsible for a variety of biochemical alterations, including a reduced accumulation of esterified cholesterol in macrophages, an increase in endothelial NO synthetase, a reduction of the inflammatory process, and an increased stability of atherosclerotic plaques [1]. Studies investigating Atorvastatin have shown that its treatment leads to significant reductions in the levels of proinflammatory cytokines (TNF, IL-1 and IL-6) [2]. Atorvastatin significantly decreased bone resorption markers, including levels of serum IL-6 [3]. Atorvastatin has been used to inhibit metalloproteinases [6,7], osteoclastogenesis and bone destruction, and the expression of the receptor activator of nuclear factorkappa B ligand (RANKL) [8]
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