Effect of adenosine A2A receptor agonist (CGS) on ischemia/reperfusion injury in isolated rat liver

ISSN： 1360-8185

Source： Apoptosis, Vol.10, Iss.5, 2005-10, pp. : 955-962

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Abstract

Ischemia/reperfusion injury during liver transplantation is a major cause of primary nonfunctioning graft for which there is no effective treatment other than retransplantation. Adenosine prevents ischemia-reperfusion-induced hepatic injury via its A2A receptors. The aim of this study was to investigate the role of A2A receptor agonist on apoptotic ischemia/reperfusion-induced hepatic injury in rats. Isolated rat livers within University of Wisconsin solution were randomly divided into four groups: (1) continuous perfusion of Krebs-Henseleit solution through the portal vein for 165 minutes (control); (2) 30-minute perfusion followed by 120 minutes of ischemia and 15 minutes of reperfusion; (3) like group 2, but with the administration of CGS 21680, an A2A receptor agonist, 30  g/100 ml, for 1 minute before ischemia; (4) like group 3, but with administration of SCH 58261, an A2A receptor antagonist. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results showed that at 1 minute of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with CGS (p < 0.05).="" on="" fluorometric="" assay,="" caspase-3="" activity="" was="" significantly="" decreased="" in="" group="" 3="" compared="" to="" group="" 2="">p < 0.0002).="" the="" reduction="" in="" postischemic="" apoptotic="" hepatic="" injury="" in="" the="" cgs-treated="" group="" was="" confirmed="" morphologically,="" by="" the="" significantly="" fewer="" apoptotic="" hepatocyte="" cells="" detected="">p < 0.05);="" immunohistochemically,="" by="" the="" significantly="" weaker="" activation="" of="" caspase-3="" compared="" to="" the="" ischemic="" group="">p < 0.05);="" and="" by="" the="" tunel="" assay="">p < 0.05).="" in="" conclusion,="" the="" administration="" of="" a2a="" receptor="" agonist="" before="" induction="" of="" ischemia="" can="" attenuate="" postischemic="" apoptotic="" hepatic="" injury="" and="" thereby="" minimize="" liver="" injury.="" apoptotic="" hepatic="" injury="" seems="" to="" be="" mediated="" through="" caspase-3="" activity.="">