Anti-inflammatory Effects Of Methanandamide On Oral Tissues Of Rats

The immunological function of the submandibular gland (SMG) maintaining the oral health is well established. Also, the endocannabinoid system plays immuno-modulatory effects in different organs of the body exposed to pathophysiological conditions. Cannabinoid receptors were identified in oral tissues such as SMG and gingiva by immuno-histochemistry. Objectives: to assess the possible anti-inflammatory effects of methanandamide, a synthetic cannabinoid receptor type 1 (CB1) selective agonist, on SMGs and gingival tissues exposed to lipopolysaccharide (LPS). Methods: gingival tissues and SMGs extracted from intact rats were used for in vitro studies and rats exposed to different experimental conditions were used for in vivo studies. Results: Methanandamide (10-9M) decreased (p<0.05) LPS (10 µg/ml) -induced tumor necrosis factor alpha (TNFa, measured by ELISA Kit) and prostaglandin E2 (measured by radioimmunoassay) release from SMGs and gingival tissues incubated in vitro (N=6 /group) in a thermostatic bath (37° C) with continuous agitation, while the CB1 selective antagonist AM251 (10-5M) blocked (p<0.05) the inhibitory effects. The in vivo studies showed that a daily local topical application of methanandamide (500 ng/ml) attenuated (p<0.05) alveolar bone loss induced by injections of 20 µl of LPS (1 mg/ml) in the gingival tissue around the neck of the first upper and lower molars of the rats (N=6/group), three times a week during 6 weeks (an infectious model of periodontitis induction). Furthermore, the treatment with methanandamide reduced (p<0.05) the LPS-increased activity of the enzyme inducible nitric oxide synthase (iNOS) measured in SMGs and gingival tissues extracted from the rats at the end of the experiment. Conclusion: The present results demonstrate the anti-inflammatory effects of methanandamide on LPS-induced oral tissues inflammation and confirm the participation of the endocannabinoid system in the oral heath of rats. (Grants: PICT 07-1016, UBACyT-O007 and UBACyT-20020090300051).