Tacrolimus Preconditioning of Rat Liver Allografts Impacts Glutathione Homeostasis and Early Reperfusion Injury

Pratschke, Sebastian; Bilzer, Manfred; Grützner, Uwe; Angele, Martin K.; Tufman, Amanda; Jauch, Karl‐Walter; Schauer, Rolf

doi:10.1016/j.jss.2011.07.045

Cited by 21 publications

(21 citation statements)

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“…BD, due to massive catecholamine release, is followed by significant hemodynamic disturbances and ischemia that occurs before organ retrieval has begun and leads to the induction of oxidative stress [1,2]. Oxidative stress has been implicated in development of complications after organ transplantation emphasizing on ischemia-reperfusion injury (IRI), delayed graft function (DGF) [3] and primary allograft dysfunction which remains a serious problem in organ transplantation [4]. The occurrence of oxidative stress as well as apoptosis and nitrosative stress induced cell damage in LD and BD is therefore of interest.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

et al. 2013

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BackgroundAs organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).MethodsBD was induced in pigs; after 12 h organ retrieval was performed; heart, liver and kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n = 6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP 70.2 was performed and immunohistochemistry used to show apoptosis and nitrosative stress induced cell damage.ResultsIn heart tissue of BD BAX, BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over-expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1, SOD2 and HSP 70.2 expression was significantly elevated in LD. Immunohistochemistry showed a significant increase in activated Caspase 3 and nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but not in heart tissue.ConclusionThe up-regulation of protective and apoptotic genes seems to be divergent in the different organs in the BD and LD setting; however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive cells in the BD setting in liver and kidney tissue whereas in heart tissue both BD and LD showed an increase.

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Section: Introductionmentioning

confidence: 99%

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

et al. 2013

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“…And also an ex vivo FK506 (tacrolimus) treatment clinically may represent a solution to this problem. Recently experimental data indicated a protective effect of an ex vivo FK506 (tacrolimus) rinse in a model of experimental liver transplantation in rats (30). In this study preservation of intracellular glutathione levels was suggested as a potential mechanism, and FK506 increases glutathione metabolism, which in turn may protect organ function by reducing ROS toxicity.…”

Section: Discussionmentioning

confidence: 72%

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

Sawada

Inoue

Tanabe³

et al. 2016

J. Med. Invest.

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: Purposes ; FK506 (strong immunosuppressive agent) was investigated experimentally whether to protect the hepatic IRI. Methods ; Warm ischemic experiment using pigs and rats were performed and examined whether FK506 is effective. Results ; The results obtained are as follows. 1. Warm ischemia allowed time of the pigs without FK506 was 150 minutes, but as for that of FK506 group, the extension of 30 minutes was got in 180 minutes. 2. Biliary excretion rate of BSP after reperfusion were better in the group of 180 minutes ischemia with FK506 than in without FK506 group. 3. Chemiluminescence intensity in the peripheral neutrophils and adhered and infiltrated leukocytes in the liver were suppressed markedly by FK506. 4. The vascular endothelium with the scanning electron microscope was relatively preserved in the FK506 group comparing to the placebo group on 30 minutes after reperfusion. 5. Stress gastric ulcer was controlled and myeloperoxidase activity in the gastric mucosa was suppressed by FK506. Conclusion ; Based on the results of theses experiments, it was suggested that FK506 has a protective effect on IRI by suppressing : the impairment of sinusoidal endothelial cells ; the activation of KCs ; the disturbance of micro-circulation ; oxidative stress ; inflammation ; and the accumulation of leukocytes.

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“…Prior to implantation, livers are rinsed with 1000 mL rinse solution containing 20 ng/ml Tacrolimus. In an experimental liver transplant model, ex vivo treatment with Tacrolimus ameliorated IRI while affecting glutathione homeostasis (80). …”

Section: Clinical Implications and Novel Therapiesmentioning

confidence: 99%

Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

et al. 2014

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Ischemia/reperfusion injury (IRI), an inherent component of transplantation, affects organ quality and transplant outcomes. Although the complexity of the pathophysiology is recognized, detailed mechanisms remain unclear, and strategies preventing the consequences of IRI have been challenging. Of critical significance appears the link between IRI, the initiation of innate immune responses, and the (potential) augmentation of adaptive immunity. An improved understanding of those complex mechanisms and interactions may pave the way for more effective treatment strategies.

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Tacrolimus Preconditioning of Rat Liver Allografts Impacts Glutathione Homeostasis and Early Reperfusion Injury

Cited by 21 publications

References 51 publications

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

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