Potential of topical application of a new chalconic compound in the modulation of periodontitis in rats

Author(s)

Angelo Constantino Camilli

• Document type: Master's Dissertation
• Press: Araraquara. 2022-04-18.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara
• Defense date: 2022-03-16
• Advisor: Morgana Rodrigues Guimarães Stabili

Abstract

Chalcones are a group of plant-derived phenolic compounds with diverse biological properties. Due to their pharmacological effects (anti-inflammatory, antioxidant, anti-osteolytic activity) and low toxicity, different synthetic chalconic derivatives, based on their natural analogues, have been investigated as therapeutic agents in inflammatory diseases such as rheumatoid arthritis, cancer and inflammatory bowel diseases, and the results have been promising. Despite the myriad of clinical and preclinical results showing the therapeutic potential of chalcones, few studies have evaluated their effects on the progression of periodontitis. Data from our research group evaluating the effect of systemic administration (orally) of a new chalconic compound (Chalcone T4), in a model of periodontal disease in rats, observed a reduction in bone loss and inflammatory infiltrate in the gingival tissues, in addition to the absence of secundary effects. Considering the anti-inflammatory potential of Chalcone T4 and the site-specific nature of periodontal disease, in this present study we evaluated the efficacy of local application of the compound directly to periodontal tissues. Chalcone T4 was diluted in 1% carbopol gel, at concentrations of 0,6mg/mL and 1,8mg/mL, and applied topically in the gingival sulcus around the first molars of the animals, for 10 days, once day. Applications began on the same day as the placement of the ligatures (baseline). On the 10th, the animals were euthanized and the gingival tissues around the tooth, and the hemi-mandibles containing the first molars were removed for the following analyses: bone resorption (bone microtomography ((µCT)), quantification of the cellular infiltrate and extracellular matrix (stereometric analysis) , analysis of the expression of inflammatory mediators (NFATc1, TNF-α, iNOS superoxide dismutase (SOD)), (RT-qPCR); expression and localization of BCL-2 (immunohistochemistry), and activation of IkBα (Western blot). The results showed that the lowest dose of the compound inhibited ligature-induced bone loss, and both doses prevented collagen matrix degradation. Decreased expression of NFATc1, TNF-α and iNOS, and increase of superoxide dismutase (SOD) (mRNA), were found in the gingival tissues of animals treated with chalcone T4. The compound also decreased the expression of BCL-2 positive cells. Interestingly, these effects were not associated with IkBα modulation. These results indicate that local application of T4 chalcone reduced bone resorption and inflammation associated with periodontitis, suggesting a therapeutic potential for the compound in this inflammatory condition. (AU)

• FAPESP's process: 20/11180-3 - Potential of a new limestone compound in the modulation of periodontal disease: a study in rats
• Grantee: Angelo Constantino Camilli
• Support Opportunities: Scholarships in Brazil - Master