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 E₂ (radioimmunoassay), nitric oxide (radioconversion of ¹⁴C-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^–8M, 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 CB₁ and CB₂ cannabinoid receptors since the injection of both antagonists together, AM251 (10^–6M) and AM630 (10^–6M) in 30 µl, prevented these effects. Conclusion: The endocannabinoid AEA diminishes the inflammatory response in periodontitis even during a stressful situation.

Protective Action of Anandamide and Its COX-2 Metabolite against L-Homocysteine-Induced NLRP3 Inflammasome Activation and Injury in Podocytes

“…Further studies are needed to address whether such approaches are also protective in glomerular injury associated with hHcys. Our finding that exogenous AEA produces anti-inflammatory effects is consistent with several reports documenting beneficial effects of exogenous AEA in inflammatory disease models, such as liver damage (Hegde et al, 2008), LPS-induced pulmonary inflammation AEA and Metabolites and NLRP3 Inflammasomes in Podocytes (Berdyshev et al, 1998), periodontitis (Rettori et al, 2012), hypoxia-ischemia injury (Lara-Celador et al, 2012), delayedtype hypersensitivity (Jackson et al, 2014), and viral demyelinating disease (Hernangomez et al, 2012).…”

Endocannabinoids and Inflammatory Response in Periodontal Ligament Cells

“…In vitro studies show that AEA reduces the production of pro-inflammatory mediators induced by P. gingivalis lipopolysaccharide (LPS) in human gingival fibroblasts [14] and promotes the proliferation of these cells [13]. Animal studies have shown that AEA and its synthetic analog methanandamide diminish the inflammatory response in experimentally induced periodontitis [16], [17]. However, the exact role of endocannabinoid system in pathogenesis of periodontal disease remains largely unknown.…”

Immunomodulatory activity of Nerium indicum through inhibition of nitric oxide and cyclooxygenase activity and modulation of TH1/TH2 cytokine balance in murine splenic lymphocytes

“…Carignan and his group (2013) reported that aliphatic n-alkanols target nuclear factor of activated T cells (NFAT) and nuclear factor kappa-b (NF-jb) situated downstream to the cell membrane. Compounds with active amide linkage such as anandamide, inhibit TNF-a and IL-1b expression in experimental inflammatory periodontitis and stress models (Rettori et al 2012). In addition, there are numerous compounds possessing active nitro groups with diverse medicinal and therapeutic properties (Kapoor et al 2003).…”