Effects of the DL76 Antagonist/Inverse Agonist of Histamine H3 Receptors on Experimental Periodontitis in Rats: Morphological Studies

Author:

Geremek Mariusz1ORCID,Drozdzowska Bogna2,Łażewska Dorota3ORCID,Kieć-Kononowicz Katarzyna3ORCID,Jochem Jerzy4

Affiliation:

1. Department of Public Health, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, 40-055 Katowice, Poland

2. Department of Pathomorphology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland

3. Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St, 30-688 Kraków, Poland

4. Department of Physiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland

Abstract

Background: Periodontitis preceded by gingivitis is the most common form of periodontal disease and occurs due to the interaction of microorganisms present in the complex bacterial aggregates of dental plaque biofilm and their metabolism products with periodontal tissues. Histamine is a heterocyclic biogenic amine acting via four types of receptors. Histamine H3 receptors act as presynaptic auto/heteroreceptors to regulate the release of histamine and other neurotransmitters. Aim: Since the nervous system is able to regulate the progression of the inflammatory process and bone metabolism, the aim of this study was to investigate the effects of DL76, which acts as an antagonist/inverse agonist of H3 receptors, on the course of experimental periodontitis. Materials and methods: This study was conducted in 24 mature male Wistar rats weighing 245–360 g, aged 6–8 weeks. A silk ligature was placed on the second maxillary molar of the right maxilla under general anesthesia. From the day of ligating, DL76 and 0.9% NaCl solutions were administered subcutaneously for 28 days in the experimental and control groups, respectively. After the experiment, histopathological, immunohistochemical and radiological examinations were performed. Results: Ligation led to the development of the inflammatory process with lymphocytic infiltration, increased epithelial RANKL and OPG expression as well as bone resorption. DL76 evoked a reduction in (1) lymphocytic infiltration, (2) RANKL and OPG expression as well as (3) bone resorption since the medians of the mesial and distal interdental spaces in the molars with induced periodontitis were 3.56-fold and 10-fold lower compared to the corresponding values in saline-treated animals with periodontitis. Conclusion: DL76 is able to inhibit the progression of experimental periodontitis in rats, as demonstrated by a reduction in the inflammatory cell infiltration, a decrease in the RANKL/RANK OPG pathway expression and a reduction in the alveolar bone resorption.

Funder

Jagiellonian University Medical College

Medical University of Silesia in Katowice

Publisher

MDPI AG

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