Open AccessProtective effect of adenosine A 2A receptor activation in small‐for‐size liver transplantation
Author(s) -
Tang LiMing,
Wang YanPeng,
Wang Ke,
Pu LiYong,
Zhang Feng,
Li XiangCheng,
Kong LianBao,
Sun BeiCheng,
Li GuoQiang,
Wang XueHao
Publication year - 2007
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2006.00394.x
Subject(s) - medicine , liver transplantation , cgs 21680 , transplantation , agonist , apoptosis , adenosine , antagonist , saline , pharmacology , endocrinology , receptor , adenosine receptor , biology , biochemistry
Summary The aim of the present study was to investigate the potential role of adenosine A 2A receptor (A 2A R) activation in small‐for‐size liver transplantation. A rat orthotopic liver transplantation model was performed by using 40% (range: 36–46%) liver grafts. Recipients were given either saline (control group) or CGS 21680 (2‐p‐(2‐Carboxyethyl)phenethylamino‐5′‐N‐ethylcarboxamidoadenosine hydrochloride, a selective A 2A R agonist), or CGS 21680+ ZM 241385 (a selective A 2A R antagonist) immediately after reperfusion for 3 h. Compared with control group, CGS 21680 used at both low dose (0.05 μ g/kg/min) and high dose (0.5 μ g/kg/min) increased the survival rate from 16.7% (2/12) to 83.3% (10/12) and 66.7% (8/12), respectively. These effects correlated with improved liver function and preserved hepatic architecture. CGS 21680 effectively decreased neutrophil infiltration, suppressed pro‐inflammatory (TNF‐ α , IL‐1 β and IL‐6) expression, promoted expression of antiapoptotic molecules, and inhibited apoptosis. The effects of CGS 21680 were prevented when ZM 241385 was co‐administrated. In conclusion, the present study showed that A 2A R activation alleviated portal hypertension, suppressed inflammatory response, reduced apoptosis, and potentiated the survival of small‐for‐size liver grafts. Our findings provide the rationale for a novel therapeutic approach using A 2A R activation to maximize the availability of small‐for‐size liver grafts.