The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion

Fundam Clin Pharmacol. 2020 Feb;34(1):80-90. doi: 10.1111/fcp.12502. Epub 2019 Aug 28.


Ischemia and reperfusion of intestinal tissue (intestinal I/R) induce disruption of ileal contractility and chain responses of inflammatory. The aim of this study was to reveal whether therapeutic value of cannabinoid 2 (CB2) receptor activity in the intestinal I/R, via to the exogenous administration of CB2 agonist (AM-1241). Intestinal I/R injury were performed through 30-min ischemia and 150-min reperfusion of mesenteric artery in Wistar rats. The pre-administered doses of 0.1, 1, and 5 mg/kg of CB2 agonist were studied to inhibit inflammation of intestinal I/R injury including ileum smooth muscle contractility, polymorphonuclear cell migration, oxidant/antioxidant defense system, and provocative cytokines. Pre-administration with CB2 receptor agonist ensured to consider improving the disrupted contractile responses in ileum smooth muscle along with decreased the formation of MDA that production of lipid peroxidation, reversed the depleted glutathione, inhibited the expression of TNF-α and of IL-1β in the intestinal I/R of rats. Taken together results of this research, the agonistic activity of CB2 receptor for healing of intestinal I/R injury is ensuring associated with anti-inflammatory mechanisms such as the inhibiting of migration of inflammatory polymorphonuclear cells that origin of acute and initial responses of inflammation, the inhibiting of production of provocative and pro-inflammatory cytokines like TNF-α and IL-1β, the rebalancing of oxidant/antioxidant redox system disrupted in injury of reperfusion period and the supporting of physiologic defensive systems in endothelial and inducible inflammatory cells.

Keywords: IL-1β; TNF-α; cannabinoid 2 receptor agonist; ileum contractility; inflammation; intestinal ischemia and reperfusion; oxidative injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Cannabinoids / administration & dosage
  • Cannabinoids / pharmacology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glutathione / metabolism
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Intestines / drug effects
  • Intestines / pathology
  • Male
  • Oxidation-Reduction / drug effects
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB2 / agonists*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology


  • AM 1241
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cannabinoids
  • Cytokines
  • Receptor, Cannabinoid, CB2
  • Glutathione