Potential of a new limestone compound in the modulation of periodontal disease: a study in rats

Abstract

Chalcones are a group of phenolic compounds derived from plants, with diverse biological properties. Due to their pharmacological effects, different synthetic chalconic derivatives, based on their natural analogues, have been investigated as therapeutic agents. Clinical and preclinical studies have demonstrated its effectiveness in the treatment of inflammatory diseases such as cancer and arthritis, and in bone pathologies such as osteoporosis and bone tumors. Chalcones can act on a number of targets in the inflammatory process, including transcription factors, adhesion molecules, intracellular signaling and inflammatory mediators that are essential in the process of osteoclast activation and differentiation. Data from our research group evaluating the effect of systemic (oral administration) of a new chalconic compound (Chalcona T4) on inflammatory bone resorption, in a model of periodontal disease, observed a reduction in bone loss and inflammatory infiltrate in the gingival tissues, in addition to the absence of side effects. Considering the anti-inflammatory potential of Chalcona T4 and the site-specific nature of periodontal disease, this study aims to evaluate, for the first time, the effectiveness of topical / local application of this new compound on inflammatory bone resorption in a disease model experimental periodontal. The hypothesis of this work is that Chalcona T4 can inhibit the progression of periodontal disease, through the modulation of biological mediators and relevant transcription factors in bone metabolism, especially through the suppression of the intracellular NF-8B signaling pathway. This hypothesis will be assessed through the following specific aim:To evaluate the effect of the local application of Chalcona T4 on the progression of periodontitis experimentally induced by ligation in rats. The analyzed outcomes will include: analysis of bone loss (bone microtomography); immunolocation and quantification of leukocytes (CD45) present in gingival tissues, as well as bone markers (OPG and RANKL) and transcription factors (RUNX-2, NFATc1 and NF-8B) by immunohistochemistry (IHC); quantification of osteoclasts identified by the positive expression of tartrate-resistant acid phosphatase enzyme (TRAP), alternatively identified by IHC; to determine a possible effect of chalcone on the phenotypic alteration of macrophages (M1 / M2) (immunofluorescence), and to investigate its influence on protein levels of NFTAc1 (western-blot). (AU)