A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NIAAA	PHARM/PHYS-6

Authors

• G Tanchian
• B Horvath
• P Mukhodpadhyay
• S Batkai
• C Goodfellow
• M Glass
• R Mechoulam
• P Pacher

Abstract

Cannabinoid 2 (CB2) receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischemia-reperfusion (I/R) injury. We have investigated the effects of a novel CB(2) receptor agonist HU-910 on liver injury inflicted by 1hour of ischemia followed by 2,6 or 24hours of reperfusion, using a well-established mouse model of segmental hepatic I/R.. HU-910 given prior to ischemia significantly attenuated the levels of I/R-induced hepatic pro-inflammatory chemokines (macrophage inflammatory protein-1α/2, monocyte chemotactic protein-1), cytokine tumor necrosis factor-α (TNF-α), and inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1h after the ischemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells, likewise the adhesion molecules expression in primary human liver sinusoidal endothelial cells stimulated with TNF-α. CB2 receptor antagonist pretreatment significantly attenuated the protective effect of HU-910, while CB1 antagonist rather tended to enhance it. HU-910 is a potent CB2 receptors agonist which may exert protective effects in various diseases associated with inflammation and tissue injury.

back to top