Aplicação tópica do gel de S-nitrosoglutationa em matriz mucoaderente modula marcadores inflamatórios na periodontite experimental em ratos

Abstract

Periodontal diseases, highly prevalent disease in worldwide population, manifest primarily in two distinct entities: plaque-induced gingivitis and periodontitis. In this study, we evaluated the effect of a formulation containing nitric oxide donor, S-nitrosoglutathione (GSNO), in mucoaderente matrix (HPMC) in experimental periodontal disease (EPD). This mucoaderente formulation allows topical application and slow diffusion of GSNO. DPE was induced by insertion of a 3.0 nylon suture around the left upper second molar. Animals was divided in groups: naive, non-treated group, and groups treated with HPMC or GSNO (0.5, 2 and 10 mM). To evaluate the GSNO effects in DPE, we measured: the rate of alveolar bone loss, serum bone alkaline phosphatase, histopathology scores, cytokine assay, immunohistochemistry for iNOS, RANK, RANKL, OPG and TRAP, nitrite and nitrate levels, glutathione (GSH) levels and malondialdehyde (MDA) levels. Gene expression TNF-α, RANK, RANK-L and OPG was measured by qPCR. The GSNO reduced the bone loss, increased bone alkaline phosphatase, decreased the inflammatory cell infiltrate, decreased the release of proinflammatory cytokines (IL-1β and TNF-α and IL-10), diminish gene expression of TNF-α, RANK and RANL/OPG and the iNOS, RANK and RANK-L protein expression, increasing OPG protein expression. Moreover, GSNO reduced oxidative stress, increasing GSH and decreasing MDA and NOx levels. In conclusion, GSNO in mucoaderente formulation promise to improve periodontal disease treatment. However, clinical trials are required to evaluate effect and toxicity GSNO.