title: Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat.
abstract: 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)-1β (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-1β 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.
  
  
  CONCLUSIONS
  The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation.
authors: Department of Physiology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina. elisarettori@yahoo.com.ar
authors: Elisa
authors: E
authors: Rettori
authors: Andrea
authors: A
authors: De Laurentiis
authors: María
authors: M
authors: Zorrilla Zubilete
authors: Valeria
authors: V
authors: Rettori
authors: Juan Carlos
authors: JC
authors: Elverdin
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000627:therapeutic use*; D011458:Prostaglandins E / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D007211:Indoles; D053583:Interleukin-1beta; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011458:Prostaglandins E; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; C103505:AM 251; D019001:Nitric Oxide Synthase; C094023:iodopravadoline; C078814:anandamide; D003345:Corticosterone