Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts.
OBJECTIVE
This study sought to investigate the protective potential of exogenous biliverdin (BV) for small-for-size rat liver transplants.


RESULTS
We employed a rat orthotopic liver transplantation model using small-for-size grafts. BV (50 mumol/kg, intravenously) given to the recipient immediately before reperfusion increased 7-day survival rates (90% vs 40% in controls) and significantly diminished hepatocyte injury, as compared with a control group. These effects correlated with improved liver function and preserved hepatic architecture. BV adjuvant increased antioxidant ability, suppressed proinflammatory tumor necrosis factor-alpha expression, down-regulated proapoptotic molecules (cytochrome C and caspase-3), and inhibited most apoptotic cells. After reperfusion, there was a significant increase of c-Jun NH(2)-terminal kinase (JNK) activation and AP-1 binding ability. BV treatment effectively repressed JNK/AP-1 activation, indicating that a beneficial effect of BV treatment may be related to suppression of the JNK/AP-1 pathway.


CONCLUSIONS
BV treatment alleviated ischemia-reperfusion injury at least in part via inhibition of the proinflammatory and proapoptotic JNK/AP-1 pathway. Our findings provide a rationale for a novel therapeutic approach using BV to maximize the availability of small-for-size liver grafts.
Tang
L-M
LM
General Surgery Department, Changzhou No. 2 Hospital Affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, China.
Wang
Y-P
YP
Wang
K
K
Pu
L-Y
LY
Zhang
F
F
Li
X-C
XC
Kong
L-B
LB
Sun
B-C
BC
Li
G-Q
GQ
Wang
X-H
XH
D000818:Animals; D017209:Apoptosis; D001664:Biliverdine / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006085:Graft Survival / Q000502:physiology; D008099:Liver / Q000033:anatomy & histology*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D001664:Biliverdine