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

Abstract

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-1β expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of IκB-α, p65, and IκB kinase (IKK)-β induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor β-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cemento-enamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1β, 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-κB pathway mediated inflammation in mouse periodontitis model.

• Authors: Xinxin Sun, Yaru Sun, Sumin Cao, Xueli Liu
• Journal: Immunity, inflammation and disease (Immun Inflamm Dis) Vol. 11 Issue 8 Pg. e959 (08 2023) ISSN: 2050-4527 [Electronic] England
• PMID: 37647428 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

Chemical References

• polysulfide
• Acetylcysteine
• Lipopolysaccharides
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Mice
• Acetylcysteine (pharmacology)
• Lipopolysaccharides (toxicity)
• Toll-Like Receptor 4 (genetics)
• Periodontitis (drug therapy)
• Tumor Necrosis Factor-alpha
• Disease Models, Animal