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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Apoptosis, Biliverdine, Enzyme-Linked Immunosorbent Assay, Graft Survival, Liver, Liver Transplantation, Male, Malondialdehyde, Rats, Rats, Sprague-Dawley, Reperfusion Injury, Transplantation, Isogeneic, Tumor Necrosis Factor-alpha.
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Does exogenous biliverdin ameliorate ischemia-reperfusion injury in small-for-size rat liver grafts? Context: This study sought to investigate the protective potential of exogenous biliverdin (BV) for small-for-size rat liver transplants. 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.
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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. Final Decision: yes