Abstract | OBJECTIVE: 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.
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Authors | L-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 |
Journal | Transplantation proceedings
(Transplant Proc)
Vol. 39
Issue 5
Pg. 1338-44
(Jun 2007)
ISSN: 0041-1345 [Print] United States |
PMID | 17580135
(Publication Type: Journal Article)
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Chemical References |
- Tumor Necrosis Factor-alpha
- Malondialdehyde
- Biliverdine
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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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