Pharmacological Targeting of Histamine H4 Receptor in Periodontal Disease

Abstract

Objective

To investigate whether histamine H₄ receptor (H₄R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva.

Methods

Bilateral EP was induced for two weeks in anesthetized male rats. The effect of systemic and local administration of H₄R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated.

Results

The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased PGE2 levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters.

Conclusions

H₄R antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H₄R could be an attractive strategy to improve periodontal health.

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