کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6105997 | 1211155 | 2013 | 7 صفحه PDF | دانلود رایگان |
Background & AimsLiver grafts obtained from healthy rat donors develop acute microcirculatory dysfunction due to cold-storage and warm-reperfusion injuries. These detrimental effects are avoided adding simvastatin to the cold-storage solution. Considering the importance of increasing organ donor pool for transplantation, we characterized whether simvastatin pretreatment can protect steatotic grafts from cold-storage and warm-reperfusion injuries.MethodsRats fed with high-fat diet received a single dose of simvastatin, or its vehicle, 30Â min before liver procurement. Grafts were then cold stored for 0Â h (control group) or 16Â h and warm reperfused. At the end of the reperfusion period, hepatic vascular resistance, endothelial function, nitric oxide pathway, cell death, oxidative stress, autophagy, and liver injury were evaluated. Hepatic vascular resistance and endothelial function were determined in a group of simvastatin-treated livers in the presence of the nitric oxide synthase inhibitor L-NNA.ResultsCold-stored rat steatotic livers exhibit increased hepatic vascular resistance and marked endothelial dysfunction, together with liver damage, oxidative stress, and low nitric oxide. Simvastatin markedly improved liver injury and prevented hepatic endothelial dysfunction. The beneficial effects of simvastatin were associated with cell death diminution, autophagy induction, and nitric oxide release. Statin-derived liver microcirculation protection was not observed when nitric oxide production was blunted.ConclusionsPretreatment of steatotic liver donors with simvastatin shortly before procurement of the liver graft strongly protects both parenchymal and endothelial components of the liver after warm reperfusion. Our data reinforce the use of statins to protect liver grafts undergoing transplantation.
Journal: Journal of Hepatology - Volume 58, Issue 6, June 2013, Pages 1140-1146