Effects of N-acetyl-L-cysteine polysulfides on periodontitis in a mouse model

Background: Polysulfides are reported to be involved in various important biological processes. N-acetyl-L-cysteine polysulfide with 2 sulfane sulfur atoms (NAC-S2) regulates diverse toll-like receptor (TLR) signaling pathways. Here, we aimed to determine the role of NAC-S2 in periodontitis and explore the potential mechanism. Methods: A periodontitis mouse model was established by ligating the subgingival between the first and second molars in wild-type, TLR4(-/-), and Myd88(-/-) mice. Results: NAC-S2 did not affect the proportion of macrophages (CD11b(+)F4/80(+)) or neutrophils (CD11b(+)GR-1(+)) in the bone marrow. Mechanically, lipopolysaccharides (LPS), Zymosan A, or poly I: C induced tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1 beta expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of I kappa B-alpha, p65, and I kappa B kinase (IKK)-beta induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor beta-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cementoenamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1 beta, while such phenomena could not be observed in TLR4 deficiency or Myd88 deficiency mice. Conclusions: All of these results indicate that NAC-S2 ameliorates TLR4/NF.B pathway mediated inflammation in mouse periodontitis model.