The relevance of the Nrf2 pathway in the progression of periodontitis, and the effects of its activation/inhibition.

Abstract

The production of antioxidant enzymes, necessary to counteract the harmful effects of oxidative stress, is in part regulated by the Nrf2 signaling pathway (nuclear erythroid factor 2 related factor 2). In addition to acting on the activation of antioxidant factors, Nrf2 is able to inhibit the activation of inflammatory cytokines and chemokines and transcription factors involved in the modulation of pro-inflammatory cytokines, and therefore, it has recently emerged as a new therapeutic target in the treatment of various diseases inflammatory. The present study aims to evaluate the protective role of the Nrf2 activator, dimethyl fumarate (DMF), on the progression of periodontitis in an experimental model of ligature-induced periodontitis in rats. DMF (50, 100 and 150 mg/kg) will be administered orally for 10 days in periodontally diseased animals. The effect of selective Nrf2 inhibition on disease progression will also be evaluated through the intraperitoneal administration of a pharmacological inhibitor (ML385, 15mg/kg). The effects of Nrf2 activation and inhibition on periodontal tissues, in different experimental groups, will be evaluated according to the following parameters: percentage of mandibular bone volume (microcomputed tomography- µCT); presence of inflammatory infiltrate and expression of Nrf2 and NF-ºB (quantification of CD45+, Nrf2+, NF- ºB cells by immunohistochemistry) in the gingival tissues; IL-6 levels (ELISA); and analysis of gingival and systemic levels of malondialdehyde (MDA) and total oxidant capacity, (by colorimetric reactions).