2-Arachidonoylglycerol Increases in Ischemia–Reperfusion Injury of the Rat Liver

Abstract

Several studies have implicated endocannabinoids in various forms of shock. However, the role of endocannabinoids in hepatic ischemia-reperfusion injury remains unclear. The purpose of this study was to evaluate the changes of two endocannabinoidsin hepatic ischemia-reperfusion injury: anandamide (ANA) and 2-arachidonoylglycerol (2-AG). Male Sprague-Dawley rats were divided into 2 groups: the short (15 min) ischemic group and the long (60 min)ischemic group in the segmental (70%) hepatic tissue. Blood levels of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), ANA, and 2-AG were examined. Serum lev-els of AST, ALT, and LDH were significantly higher in the long-ischemia group than in the short-ischemia group. Plasma levels of 2-AG showed similar augmentation prior to and after reperfusion in both the short- and long-ischemia groups, although plasma 2-AG lev-els tended to be higher in the long-ischemia group than in the short-ischemia group. Plasma levels of ANA were augmented in the early phase of reperfusion in the short-ischemia group and did not differ significantly from the normal level with time after reperfusion in the long-ischemia group. These results suggest that the endocannabinoid 2-AG increases in hepatic ischemia-reperfusion injury of rats, rather than ANA.

Endocannabinoids and Reactive Nitrogen and Oxygen Species in Neuropathologies

“…It is noteworthy that there are at least two reports of increases in anandamide levels with no change in 2-arachidonoylglycerol levels following ischemia (Berger et al 2004;Hansen et al 2001b). This is in sharp contrast to the findings in the hepatic ischemiareperfusion model (Kurabayashi et al 2005) or an experimental acute myocardial infarction model (Wagner et al 2001), in which anandamide and 2-arachidonoylglycerol levels increased concurrently. The ischemic injury-induced elevations in endocannabinoid content, together with evidence that activation of the CB 1 receptor resulted in reduced central nervous system (CNS) excitability, implies that the endocannabinoid system comprises an endogenous protective mechanism during CNS injury (Mechoulam 2002;Mechoulam et al 2002b).…”

Pivotal Advance: Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis

“…The role of CB 2 receptors in I/R injury is supported further by increased accumulation of CB 2 -positive macrophages derived from resident microglia and/or invading monocytes following cerebral I/R [48]. Several studies have reported increased endocannabinoid levels following cerebral [18,[49][50][51][52] and hepatic I/R injury [44,53]; however, the role of endocannabinoids in I/R injury remains to be a controversial issue requiring further clarification. One possibility is that endocannabinoids released during I/R may try to limit the hepatic injury by modulating the expression of adhesion molecules and the infiltration and activation of inflammatory cells (mononuclear and polymorpho-nuclear leukocytes are known to express CB 2 receptors [6,21]) by CB 2 -dependent mechanisms.…”

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

“…CB 2 receptor mRNA was also detected in cirrhotic but not in normal liver tissue . Endocannabinoids are detectable in the liver or liver cells both in animals and humans at levels similar to those in the brain and play an important role under various physiological and pathophysiological conditions Kurabayashi et al, 2005;Osei-Hyiaman et al, 2005b) (see also section III.A.3. ).…”