Antimicrobial and Anti-inflammatory Effects of Simvastatin as an Intracanal Medication

Successful endodontic treatment and a predictable outcome can only be achieved by effective root canal debridement, irrigation, and elimination of microorganisms . The outcome of endodontic treatment performed in controlled clinical environment has demonstrated success rate around 90%. In certain cases, endodontic treatment may fail, one of the most common reasons is inability to eliminate microorganisms from the root canal. When non-surgical root canal therapy fails, the treatment options include orthograde re-treatment, periradicular surgery, or extraction. Simvastatin (SIM) is a drug used primarily to treat hyperlipidemia and protect against cardiovascular diseases. It has been shown to possess pleiotropic effects such as antimicrobial, anti-inflammatory, immunomodulatory, antioxidant, and bone-forming properties . The side chain of this material has a single methyl group. It inhibits hydroxymethyl glutarylcoenzyme reductase that prevents endogenous cholesterol synthesis

It has been reported that the inflamed/infected periodontal/endodontic content influence cytokines release . These inflammatory mediators, such as interleukin (IL)-1β, tumor necrosis factor α (TNF-α), and prostaglandin E2 (PGE2), have been detected in periapical tissues and root canal exudates . Proinflammatory cytokines are able to stimulate, either directly or indirectly, the release of matrix metalloproteinases (MMPs) in the periapical/periodontal region, maintaining a persistent inflammatory process. MMPs are deeply involved in the pathogenesis of pulp, periodontal, and periapical tissue destruction. As a Gram-positive, facultative anaerobe, Enterococcus Faecalis (E. Faecalis) can survive root canal treatment . It can form biofilms and survive prolonged periods of nutritional deprivation. It can also resist acidic and basic conditions and is hard to eradicate . E. Faecalis is responsible for 20-70% of endodontic failures and secondary endodontic infections . Due to biofilm development and the organism's physicochemical characteristics, which enable it to alter the prevailing environmental and nutritional conditions, it can even thrive in constrained environments . Accumulated evidence indicates that the tissue destruction in endodontic and periodontal infections is due to host-derived cytokines induced by lipopolysaccharides (LPS/endotoxins), acting as the major components of the outer leaflet of the outer membrane of gram-negative bacteria. Calcium hydroxide (Ca (OH)2) has been widely used as an intracanal medicament for retreatment of such failed cases, due to its high pH, its ability to stimulate mineralization, its antibacterial properties, and its tissue-dissolving capability . Hydroxyl ions create free radicals that destroy components of bacterial cell membranes. These free radicals react with bacterial DNA inhibiting DNA replication and cell activity, and cause mutations. Also, the alkaline pH of calcium hydroxide alters enzyme activity, disrupting cellular metabolism and structural proteins . Simvastatin enhances alkaline phosphatase activity and mineralization and increases the expression of bone sialoprotein, osteocalcin, and type I collagen, and it is shown to have an anti-inflammatory effect by decreasing the production of interleukin-6 and interleukin-8. SIM is reported to stimulate vascular endothelial growth factor (VEGF) release in a dose dependent manner, and the authors of a previous study suggested that statins may promote osteoblast differentiation and bone nodule formation by stimulating VEGF expression in bone tissue. Simvastatin is also a renowned safe and affordable medication. It is a novel medicinal substance that is still undergoing dental research . Various animal and clinical studies showed that SIM assists in bone regeneration as well as the anti-inflammatory effect when delivered or applied locally. Periapical radiography is an essential resource in endodontic diagnosis because it offers important evidence on the progression, regression, and persistence of apical periodontitis (AP) . It is known that periapical radiolucency might not be visible radiographically, although they exist clinically. Conventional radiographs used for the management of endodontic problems yield limited information because of the two-dimensional (2D) nature of the images produced, geometric distortion and anatomical noise.