Papel regulatório da via de sinalização NRF2/HO-1 em modelos in vitro de periodontite: uma revisão sistemática

Abstract

The etiopathogenesis of periodontitis is highlighted by the presence of the infectious agent (bacterial biofilm) and the host's immune-inflammatory response, determining the generation of inflammatory mediators. The aim of the study was to evaluate the role of activation of the Nrf2/HO-1 pathway in preclinical trials of periodontitis through a systematic review. This is a systematic review. A search was performed in databases and in the gray literature: Medline/Pubmed, Lilacs, Embase, Scopus, Livivo, Cochrane, Web of Science and in the gray literature google academic, pubmed central and open thesis, using a combination of predefined MeSH controlled terms and/or (DeCS) and free terms using Boolean operators (OR, AND). As inclusion criteria: studies with pre-clinical in vitro trials that addressed the NRF2-HO1 signaling pathway in the development of periodontitis through techniques of analysis of inflammatory markers published in any language without publication time interval. And exclusion criteria: in silico and in vivo studies with the NRF2/HO-1 signaling pathway different from periodontitis and that used the techniques of ICC, IF, qRT-PCR, WB and ELISA that did not present relevant primers, antibodies and proteins for the study. As primary results we had the demonstration of antiresorptive activity and involvement of the NrF2/HO-1 pathway and secondary results of Anti-inflammatory/immunomodulatory activity. The synthesis of the review results was carried out in a descriptive way and through meta-analysis. To assess the risk of bias, the free Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) was used. The systematic review sample consisted of 27 primary studies. The studies were linked to 5 different countries. The cell types most used in the studies were RAW 264.7 cells, followed by HPDL cells. It has been shown that several treatments performed such as LIPUS, quercetin, DMF for antiresorptive activity recovered mRNA and protein levels of osteoblast differentiation markers. They also promoted HO-1 expression inducing Nrf2 translocation to the nucleus and Nrf2 deficiency promoting the formation of multinucleated osteoclasts, resorption depressions and also led to increased oxidative stress and significant reductions in ROS levels. It is concluded that the results presented in this systematic review suggest evidence to characterize the involvement of the NrF2-HO-1 pathway in the pathogenesis of periodontitis.