Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation.
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 microg/kg/min) and high dose (0.5 microg/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-alpha, IL-1beta 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.
Tang
Li-Ming
LM
The Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Wang
Yan-Peng
YP
Wang
Ke
K
Pu
Li-Yong
LY
Zhang
Feng
F
Li
Xiang-Cheng
XC
Kong
Lian-Bao
LB
Sun
Bei-Cheng
BC
Li
Guo-Qiang
GQ
Wang
Xue-Hao
XH
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000502:physiology; D006085:Graft Survival; D007249:Inflammation / Q000517:prevention & control; D008099:Liver / Q000033:anatomy & histology* / Q000166:cytology / Q000502:physiology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009195:Peroxidase / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D015424:Reperfusion; D014185:Transplantation, Isogeneic / Q000502:physiology
D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D009195:Peroxidase; D000241:Adenosine