title: Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts.
abstract: 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.
authors.affiliation: General Surgery Department, Changzhou No. 2 Hospital Affiliated with Nanjing Medical University, Changzhou, Jiangsu Province, China.
authors.forename: L-M
authors.initials: LM
authors.lastname: Tang
authors.forename: Y-P
authors.initials: YP
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: L-Y
authors.initials: LY
authors.lastname: Pu
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: X-C
authors.initials: XC
authors.lastname: Li
authors.forename: L-B
authors.initials: LB
authors.lastname: Kong
authors.forename: B-C
authors.initials: BC
authors.lastname: Sun
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Li
authors.forename: X-H
authors.initials: XH
authors.lastname: Wang
mesh_terms: 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
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D001664:Biliverdine