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Anti‐Inflammatory and Osteoprotective Effects of Cannabinoid‐2 Receptor Agonist HU‐308 in a Rat Model of Lipopolysaccharide‐Induced Periodontitis
Author(s) -
Ossola Cesar A.,
Surkin Pablo N.,
Mohn Claudia E.,
Elverdin Juan C.,
FernándezSolari Javier
Publication year - 2016
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2016.150612
Subject(s) - periodontitis , lipopolysaccharide , medicine , endocrinology , agonist , tumor necrosis factor alpha , dental alveolus , cannabinoid , porphyromonas gingivalis , receptor , dentistry
Background: Anti‐inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid‐2 receptor agonist HU‐308 in the oral health of rats subjected to lipopolysaccharide (LPS)‐induced periodontitis. Methods: Twenty‐four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU‐308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU‐308 (500 ng/mL) was applied topically to the GT daily. Results: Alveolar bone loss resulting from LPS‐induced periodontitis was significantly attenuated with HU‐308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS‐injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 ± 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 ± 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 ± 25.63 pg/mg protein versus LPS+HU: 95.89 ± 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E 2 (PGE 2 ) (LPS: 159.20 ± 38.70 pg/mg wet weight versus LPS+HU: 71.25 ± 17.75 pg/mg wet weight; P <0.05). Additionally, HU‐308 treatment prevented the inhibitory effect of LPS‐induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE 2 content, which were increased by LPS‐induced periodontitis in the submandibular gland, returned to control values after HU‐308 treatment. Conclusion: This study demonstrates anti‐inflammatory, osteoprotective, and prohomeostatic effects of HU‐308 in oral tissues of rats with LPS‐induced periodontitis.