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

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.

Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat.

OBJECTIVE: Periodontitis is an infectious disease leading to inflammation and destruction of tissue surrounding and supporting the tooth. The progress of the inflammatory response depends on the host's immune system and risk factors such as stress. The aim of the present study was to investigate the role of the endocannabinoid anandamide (AEA) in experimental periodontitis with restraint stress, since the endocannabinoid system is known to modulate the hypothalamo-pituitary-adrenal axis as well as immune functions and has been found in human gingival tissues. METHODS: Experimental periodontitis was induced by ligature around first inferior molars and immobilization stress for 2 h twice daily for 7 days in a rat model. RESULTS: Corticosterone plasma levels, locomotor activity, adrenal gland weight and bone loss were increased in periodontitis and stress groups, and there was also less weight gain. The inflammatory parameters such as prostaglandin E(2) (radioimmunoassay), nitric oxide (radioconversion of (14)C-arginine), tumor necrosis factor (TNF)-α (ELISA) and interleukin (IL)-1ß (Western blot) measured in the gingival tissue were significantly increased in the periodontitis groups compared to the control group. Local injection of AEA (10(-8)M, 30 µl) decreased corticosterone plasma levels and the content of the cytokines TNF-α and IL-1ß in gingival tissue in periodontitis-stress groups. These AEA-induced inhibitions were mediated by CB(1) and CB(2) cannabinoid receptors since the injection of both antagonists together, AM251 (10(-6)M) and AM630 (10(-6)M) in 30 µl, prevented these effects. CONCLUSION: The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation.

[Antiinflammatory drugs in periodontology. Therapeutic perspectives]. / I farmaci antiflogistici in parodontologia. Prospettive terapeutiche.

The authors, through a critical review of the literature, describe the effects of antiinflammatory drugs on periodontal disease as they result from experimental trials and epidemiological observations. Furthermore the authors emphasize the possible application of such pharmacological substances in the near future as an additional instrument in the therapy of periodontal disease.

Antiarrhythmic effects of arachidonic, linoleic, linolenic, and oleic acid, and the influence of indomethacin and polyphloretinephosphate.

Intravenous application of arachidonic and linoleic acid induced strong antiarrhythmic effects demonstrated on three models of experimental arrhythmias. In contrast, linolenic and oleic acid were poorly effective. The antiarrhythmic action of the unsaturated fatty acids required 10- to 1000-fold higher doses in comparison with the most effective prostaglandins. Indomethacin decreased the antidysrhythmic action of arachidonic and linoleic acid; PG efficiency remained unaffected. Polyphloretinphosphate markedly reduced the improvement of aconitine arrhythmia by PGs, the decrease of the antidysrhythmic effects of arachidonic and linoleic acid was without statistical significance. The results suggest an important role of PG synthesis for the antiarrhythmic effect of polyunsaturated fatty acids.