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Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts.

AbstractOBJECTIVE:
This study sought to investigate the protective potential of exogenous biliverdin (BV) for small-for-size rat liver transplants.
METHODS AND 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.
AuthorsL-M Tang, Y-P Wang, K Wang, L-Y Pu, F Zhang, X-C Li, L-B Kong, B-C Sun, G-Q Li, X-H Wang
JournalTransplantation proceedings (Transplant Proc) Vol. 39 Issue 5 Pg. 1338-44 (Jun 2007) ISSN: 0041-1345 [Print] United States
PMID17580135 (Publication Type: Journal Article)
Chemical References
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Biliverdine
Topics
  • Animals
  • Apoptosis
  • Biliverdine (therapeutic use)
  • Enzyme-Linked Immunosorbent Assay (methods)
  • Graft Survival (physiology)
  • Liver (anatomy & histology)
  • Liver Transplantation (adverse effects, pathology)
  • Male
  • Malondialdehyde (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (prevention & control)
  • Transplantation, Isogeneic
  • Tumor Necrosis Factor-alpha (analysis)

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