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Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation

, : Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation. Journal of Gastroenterology and Hepatology 27(4): 832-840

Ischemia reperfusion injury (IRI) remains a major cause of graft injury, dysfunction and even failure post-transplantation. Heme oxygenase 1 (HO-1) has been found to be an attractive target for anti-inflammatory therapies and a potential candidate responsible for cell injury. The objective of this study was to investigate whether preconditioning the donor liver with Nodosin perfusion upregulates HO-1 and then lessens IRI in rat models. Wistar rats were divided into four groups: experimental group, control group, positive control group and negative control group in which the donor liver was preconditioned with Nodosin, lactated ringer's solution, cobalt protoporphyrin and zinc protoporphyrin perfusion, respectively. We measured HO-1 expression and enzyme activity in rat livers of each group ex vivo at 0, 1 and 2 h after perfusion. At 1 h after perfusion, donor livers of Wistar rats were transplanted into Sprague-Dawley rats orthotopically. Serum transaminase levels, degree of cell apoptosis and Suzuki's score were used to assess ischemia/reperfusion injury in recipients at 24 h after transplantation. Ex vivo, donor liver preconditioning with Nodosin perfusion induced HO-1 expression and enzyme activity significantly, compared with the control group (P < 0.05). In vivo, serum transaminase levels, cell apoptosis degree and Suzuki's score of representative recipients in the Nodosin group were lower than that in the control group (P < 0.05). Preconditioning with Nodosin perfusion induced HO-1 protein mainly in Kupffer cells. This study suggests that preconditioning with Nodosin perfusion provides a potential protective effect through inducing HO-1 expression to attenuate ischemia/reperfusion injury in liver transplantation.


PMID: 22098251

DOI: 10.1111/j.1440-1746.2011.06966.x

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