Long-term treatment with methanandamide attenuates LPS-induced periodontitis in rats

Inflamm Res. 2012 Sep;61(9):941-8. doi: 10.1007/s00011-012-0485-z. Epub 2012 May 12.

Abstract

Objective: Evidence exists of the anti-inflammatory and immunological properties of endocannabinoids in various tissues; the aim of the present study was therefore to assess the effect of long-term treatment with the synthetic cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in rats.

Materials and methods: Periodontitis was induced by injecting LPS (1 mg/ml) into the gingiva around the neck of the first upper and lower molars, and into the inter-dental space between the first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week.

Results: Long-term treatment with topical Meth-AEA (500 ng/ml), applied daily to gingival tissue of rats induced with periodontitis, significantly diminished the alveolar bone loss, measured as the distance between the cemento-enamel junction and the alveolar crest, in both maxillary and mandibular first molars, compared to rats without treatment (P < 0.05). The treatment also reduced the production of some biological mediators of periodontal disease augmented by LPS, such as tumor necrosis factor alpha (from 119.4 ± 9.9 pg/mg protein to 75.1 ± 10.8, P < 0.05) and nitric oxide produced by inducible nitric oxide synthase (from 507.7 ± 107.1 pmol/min/mg protein to 163.1 ± 53.9, P < 0.01).

Conclusion: These results demonstrate the beneficial effects of treatment with Meth-AEA on gingival tissue of rats with periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / metabolism
  • Alveolar Bone Loss / pathology
  • Alveolar Bone Loss / prevention & control*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Arachidonic Acids / pharmacology
  • Arachidonic Acids / therapeutic use*
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • In Vitro Techniques
  • Lipopolysaccharides
  • Male
  • Nitric Oxide Synthase Type II / metabolism
  • Periodontitis / chemically induced
  • Periodontitis / drug therapy*
  • Periodontitis / metabolism
  • Periodontitis / pathology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / agonists
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Arachidonic Acids
  • Lipopolysaccharides
  • Receptor, Cannabinoid, CB1
  • Tumor Necrosis Factor-alpha
  • methanandamide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Dinoprostone