Subnormothermic isolated organ perfusion with Nicorandil increased cold ischemic tolerance of liver in experimental model

2021 ◽  
pp. 1-12
Author(s):  
Luca Erlitz ◽  
Caleb Ibitamuno ◽  
Benedek Kasza ◽  
Vivien Telek ◽  
Péter Hardi ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Liver Perfusion ◽  
Ischemic Tolerance ◽  
Organ Perfusion ◽  
Hepatic Ischemia ◽  
Rat Liver Perfusion ◽  
Isolated Organ Perfusion

BACKGROUND: The cold ischemia –reperfusion injury may lead to microcirculatory disturbances, hepatocellular swelling, inflammation, and organ dysfunction. Nicorandil is an anti-ischemic, ATP-sensitive potassium (KATP) channel opener drug and has proved its effectiveness against hepatic Ischemia/Reperfusion (I/R) injury. OBJECTIVE: This study aimed to investigate the effect of Nicorandil on mitochondrial apoptosis, oxidative stress, inflammation, histopathological changes, and cold ischemic tolerance of the liver in an ex vivo experimental isolated-organ-perfusion model. METHODS: We used an ex vivo isolated rat liver perfusion system for this study. The grafts were retrieved from male Wistar rats (n = 5 in each), preserved in cold storage (CS) for 2 or 4 hours (group 1, 2), or perfused for 2 or 4 hours (group 3, 4) immediately after removal with Krebs Henseleit Buffer (KHB) solution or Nicorandil containing KHB solution under subnormothermic (22–25°C) conditions (group 5, 6). After 15 minutes incubation at room temperature, the livers were reperfused with acellular, oxygenated solution under normothermic condition for 60 minutes. RESULTS: In the Nicorandil perfused groups, significantly decreased liver enzymes, GLDH, TNF-alpha, and IL-1ß were measured from the perfusate. Antioxidant enzymactivity was higher in the perfused groups. Histopathological examination showed ameliorated tissue deterioration, preserved parenchymal structure, decreased apoptosis, and increased Bcl-2 activity in the Nicorandil perfused groups. CONCLUSIONS: Perfusion with Nicorandil containing KHB solution may increase cold ischemic tolerance of the liver via mitochondrial protection which can be a potential therapeutic target to improve graft survival during transplantation.

scholarly journals Pharmacological Benefits and Risk of Using Hormones in Organ Perfusion and Preservation Solutions in the Aspect of Minimizing Hepatic Ischemia-Reperfusion Injury during Storage

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Aneta Ostróżka-Cieślik ◽  
Barbara Dolińska
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Perfusion ◽  
The Body ◽  
Valuable Component ◽  
Hepatic Ischemia ◽  
Current State ◽  
Vital Functions ◽  
Preservation Solutions ◽  
Hepatic Ischemia Reperfusion

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body.

scholarly journals Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Iman O. Sherif ◽  
Nora H. Al-Shaalan
Keyword(s):  
Signaling Pathway ◽  
Normal Saline ◽  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Sham Operation ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions.

Effect of Nutritional Status on Oxidative Stress in an Ex Vivo  Perfused Rat Liver

2005 ◽  
Vol 103 (5) ◽  
pp. 978-986 ◽  
Author(s):  
Michaela Stadler ◽  
Vincent Nuyens ◽  
Laurence Seidel ◽  
Adelin Albert ◽  
Jean G. Boogaerts
Keyword(s):  
Liver Injury ◽  
Cytochrome C ◽  
Nutritional Status ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Free Access ◽  
Hepatic Ischemia

Background Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Methods Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Results Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. Conclusions In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

scholarly journals Effect of simvastatin in hepatic ischemia and reperfusion in rats

2012 ◽  
Vol 3 (1) ◽  
pp. 17 ◽  
Author(s):  
Marília Daniela Ferreira Carvalho ◽  
Laís Izabel Maia Melo ◽  
Maria Clara Medeiros Chacon ◽  
Daniel Costa Rodrigues Farias ◽  
Ítalo Medeiros de Azevedo ◽  
...  
Keyword(s):  
Liver Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Lactic Dehydrogenase ◽  
Ischemia And Reperfusion ◽  
Hepatic Ischemia ◽  
Simvastatin Group

Purpose: Liver injury induced by ischemia and reperfusion is frequently observed in the immediate postoperative period in liver transplantation and partial hepatectomy, when the liver is subjected to a period of partial or total ischemia at various times. The present study aimed to evaluate the effect of simvastatin in preventing liver ischemia-reperfusion injury in rats, using the biodistribution of radiopharmaceuticals, biochemical, immunological and histological analysis. Methods: Eighteen Wistar rats were randomly divided into three equal groups of six each. Group sham; Group IR (isquemia of left and medium hepatic lobes for 45 min; reperfusion for 24 hs); and IR simvastatin group. Animals from IR simvastatin group were treated with simvastatin microemulsion at a dose of 10mg/kg v.o. (gavage) once daily for 5 days before ischemia and reperfusion (IR). Results: Both the right and the left hepatic lobe had higher uptake of fitate-99mTc04 radioactivity in group IR simvastatin than in group IR (p<0.05). The plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) were measured at the end of each experiment. Simvastatin pretreatment led to a profound decrease in plasma enzyme levels compared with IR rats (p≤0.001). Histopathological examination revealed necrotic areas predominantly in the perivenular zone, cytoplasm vacuolization and sinusoidal congestion in an IR group rats. Simvastatin pretreatment strongly protected livers from these changes. Conclusion: In summary, our study provides the evidence that pretreatment with simvastatin protected rat livers from ischemia/reperfusion injury in vivo. This protective effect was validated by a decrease of plasma liver enzymes and histopathological features of liver injury, as well as by biodistribution of fitate-Tc99m in liver tissue.

scholarly journals The Protective Effects of Trypsin Inhibitor on Hepatic Ischemia-Reperfusion Injury and Liver Graft Survival

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Lianyue Guan ◽  
Hongyu Liu ◽  
Peiyao Fu ◽  
Zhuonan Li ◽  
Peidong Li ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Graft Survival ◽  
Trypsin Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Perfusion ◽  
Liver Graft ◽  
Dependent Manner ◽  
Protective Effects ◽  
Hepatic Ischemia

The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringer’s (LR) solution for liver perfusion and preservationin vitroor combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic geneBcl-2and decreasing the expression of the proapoptosis genes ofCaspase-3andBax, and further protects hepatocytes from apoptotic death and improves liver function.

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