Curcumin is the major biologically-active compound derived from the Curcuma longa plant. There are numerous biological activities reported for curcumin, and its immunomodulatory effects have been explored for therapeutic potential in various conditions associated with immune/inflammatory response, including rheumatoid arthritis, cancer, inflammatory bowel diseases and periodontitis. In spite of promising therapeutic potential, curcumin has important limitations that impair its clinical application, such as low bioavailability, reduced absorption in the gastrointestinal tract, short plasmatic half-life and rapid metabolic inactivation and excretion. Incorporation of curcumin in nanoparticle vehicle (nanocurcumin) may bypass some of these limitations, allowing local application and improving its pharmacological properties, which in turn may enhance its biological effects. Most preclinical studies investigating of curcumin in periodontitis use a preventive experimental model in which curcumin is administered simultaneously with the induction of the disease. Using this preventive approach, recent results from our group have shown that topical application of nanocurcumin attenuated bone resorption and inflammation in a model of LPS-induced periodontitis in rats. Based on these results, a subsequent study by our research group assessed the effects of nanocurcumin on periodontal repair, indicating that local application of nanocurcumin favored bone repair in an experimental model of periodontitis repair (i.e., curcumin is administered after removal of disease-inducing stimulus). However, the effects of nanocurcumin on non-mineralized connective tissue still need to be investigated. Thus, the objective of this study is to evaluate the effect of topical application of nanocurcumin in the repair of non-mineralized connective tissue, using the murine experimental model of periodontal repair. The hypothesis is that nanocurcumin promotes repair of non-mineralized connective tissue by increasing the content/organization of collagen fibers in periodontal connective tissue and that this effect involves the modulation of mediators related to tissue repair. This hypothesis will be tested in the following specific objectives: (I) To evaluate the effect of topical application of nanocurcumin on the content of collagen fibers of the gingival tissue in a experimental rat model of periodontal repair: histological sections will be used for picrosirius staining and analysis of the region of interest. (II) evaluate the influence of nanocurcumin on the expression of mediators related to tissue repair: gene expression of Fsp1, iNos, Col1a1, Arginase and Cd11b by RT-qPCR; expression and immunolocalization of iNOS and FGF2 by immunohistochemistry.
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