N-Phenacylthiazolium Bromide Inhibits the Advanced Glycation End Product (AGE)-AGE Receptor Axis to Modulate Experimental Periodontitis in Rats

Background: Advanced glycation end products (AGEs) are involved in the inflammatory process and are considered to be etiologic factors of diabetic periodontitis. The purpose of this study is to investigate the capability of N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker, in the modulation of periodontitis in various disease phases. Methods: Mitogenesis and cytotoxicity of human periodontal ligament cells (hPDLCs) undergoing PTB treatment were evaluated in vitro. In vivo biomodulation was investigated by systemically administering PTB in the induction, progression, and recovery phases of ligature-induced periodontitis in rats, with the results evaluated by microcomputed tomography, histology, immunohistochemistry of the AGE and AGE receptor (RAGE), and gene expression of tumor necrosis factor-alpha (TNF-alpha), RAGE, periostin, fibronectin, and type I collagen. Results: Significantly promoted mitogenesis and reduced cytotoxicity of hPDLCs were noted with 0.05 to 0.1 mM PTB treatment at 24 hours. Systemic PTB administration significantly reduced periodontal bone loss, AGE deposition, and expressions of TNF-alpha and RAGE but elevated the periostin level in all three phases of periodontitis. Conclusion: PTB inhibits the induction and progression of periodontitis and facilitates its recovery via improving cellular viability and inhibiting the AGE-RAGE axis.