New Possible Therapeutic Adjuvants For The Management Of Periodontal Inflammation

Objectives: In healthy gingival sulci, tooth-adherent microbial biofilms induce an inflammatory exudate that promotes colonization by a successor microbiota responsible for a persistent inflammatory response in the periodontal tissues. Potential therapy is to suppress development of the successor microbiota, or reduce the excessive inflammatory host response. In dental biofilms, Eikenella corrodens and Capnocytophaga spp. produce lysine decarboxylase which converts the amino acid lysine to cadaverine. Lysine depletion and cadaverine production promote successor dental biofilm accumulation and halitosis. The aims of our work were to study whether the development of experimental periodontal inflammation was retarded by inhibiting biofilm lysine decarboxylase enzyme activity or by administering an anti-inflammatory peptide, BPC157. This peptide was originally isolated from gastric juice and was found to have wound healing and osteogenic effects.

Methods: Besides plaque index and gingival crevicular fluid volume, lysine and cadaverine were measured from biofilm samples by laser-induced fluorescence after capillary electrophoresis before and after treatment with the bacterial lysine decarboxylase inhibitor tranexamic acid in a human oral hygiene restriction model. We investigated gingival capillary permeability by Evans-blue extravasation, gingival blood flow by laser Doppler flowmetry, alveolar bone morphometric parameters by microCT, and osteoblast functional activity by nanoSPECT/CT before and after BPC157 administration in a ligature-induced periodontitis model in rats.

Results: The activity of plaque lysine decarboxylase increased during experimental gingivitis. Tranexamic acid inhibited plaque development, the exudation of gingival crevicular fluid and cadaverine production in the biofilm. BPC157 had no effect on gingival blood flow, but it significantly reduced plasma extravasation, inflammatory histological alterations, as well as alveolar bone resorption.

Conclusions: Plaque cadaverine content may be a biomarker for diagnosis or for the examination of therapeutic response. Lysine decarboxylase enzyme inhibitors and the anti-inflammatory peptide BPC157 are potential new candidates for controlling periodontal disease.

Supports: Hungarian NKTH/ALAP2-9/2006, OTKA T49708 and 83915, TÁMOP-4.2.1/B-09/1/KMR-2010-0001.