Estudo do potencial terapêutico e profilático de N-Acetil-Cisteína na modulação da resposta imunológia na doença periodontal

Abstract

Periodontal diseases have as a main component and inductor a bacterial dental biofilm and are defined as an inflammation which affects the integrity of the dental tissues. Recent studies estimate that 47.2 % of individuals in the United States have some form of periodontitis. The main periodontopathic bacteria are: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (P. gingivalis), Treponema denticola (T. denticola ) and Tannerella forsythia ( T. forsythia ). These bacteria can induce a chronic and intense immune response. It is well established that immunity is dependent on two types of immune responses: cell mediated and humoral response. It has been suggested that the progression of inflammation and alveolar bone loss in periodontal disease is due to a combination of factors such as the presence of periodontal bacteria, elevated levels of inflammatory cytokines (e.g. TNF-α, IL -1 β , IL- 6 and IL-17), production and activation of MMPs and RANKL and relative low levels of modulatory cytokine IL10. Glutathione (GSH) is a tripeptide thiol found free in the cytosol, with the ability to reduce reactive oxygen species and nitrogen compounds. Moreover, GSH plays an important role in the modulation of immune responses. Low levels of GSH and oxidative stress have been linked to chronic diseases. GSH participates in antigen processing and affects the profile of cytokines by inhibiting NF-kB. N-acetylcysteine (NAC) is an acetylated cysteine variant that is converted into metabolites capable of stimulating the synthesis of GSH. NAC has been shown to decrease bone loss in diabetic rats and inhibit expression of inflammatory cytokines in gingival fibroblasts. Therefore, because of its importance in protecting rats to periodontal bone loss and knowing that NAC possess the ability to modulate the immune response, this study aims to assess the effects of NAC in the modulation of immunological and clinical characteristics in periodontal disease. Thus, a study involving NAC treatment in experimental periodontal disease in mice infected with Aa and in peripheral blood from healthy donors stimulated with periodontal periodontal bacteria Aa , P. gingivalis, and T. denticola was designed. We analyzed: 1- alveolar bone loss; 2- myeloperoxidase activity, 3- GSH quantification in peripheral blood, and 4- cytokines and markers for lymphocytes and monocytes activation in peripheral human blood. The results showed that: 1 - NAC reduces alveolar bone loss in animals infected with Aa; 2 - NAC negatively modulates the activity of myeloperoxidase in infected animals with NAC treatment; 3 - NAC decreases oxidative stress in the peripheral blood of infected animals; 4 - NAC negatively modulates proinflammatory cytokines (TNF- α and IL-17) and positively modulates regulatory cytokine (IL - 10); 5 - in humans, NAC is able to enhance activity of CD8 + T lymphocytes. Thus, NAC showed a modulatory effect on experimental periodontitis in mice and an activating effect on human lymphocytes in vitro upon stimulation with periodontal bacteria. Together, these data suggest that NAC is a promising agent for the local prevention and treatment of periodontal diseases.