New Insights into the Liver–Visceral Adipose Axis During Hepatic Resection and Liver Transplantation

In the last decade, adipose tissue has emerged as an endocrine organ with a key role in energy homeostasis. In addition, there is close crosstalk between the adipose tissue and the liver, since pro- and anti-inflammatory substances produced at the visceral adipose tissue level directly target the liver through the portal vein. During surgical procedures, including hepatic resection and liver transplantation, ischemia–reperfusion injury induces damage and regenerative failure. It has been suggested that adipose tissue is associated with both pathological or, on the contrary, with protective effects on damage and regenerative response after liver surgery. The present review aims to summarize the current knowledge on the crosstalk between the adipose tissue and the liver during liver surgery. Therapeutic strategies as well as the clinical and scientific controversies in this field are discussed. The different experimental models, such as lipectomy, to evaluate the role of adipose tissue in both steatotic and nonsteatotic livers undergoing surgery, are described. Such information may be useful for the establishment of protective strategies aimed at regulating the liver–visceral adipose tissue axis and improving the postoperative outcomes in clinical liver surgery.

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Impact of Ischemic Preconditioning on Outcome in Clinical Liver Surgery: A Systematic Review

BioMed Research International ◽

10.1155/2015/370451 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Michael J. J. Chu ◽

Ryash Vather ◽

Anthony J. R. Hickey ◽

Anthony R. J. Phillips ◽

Adam S. J. R. Bartlett

Keyword(s):

Systematic Review ◽

Liver Transplantation ◽

Liver Resection ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Liver Surgery ◽

Clinical Studies ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hepatocellular Damage

Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery.Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies.Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection.Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC.

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Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00342.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. G15-G26 ◽

Cited By ~ 556

Author(s):

Hartmut Jaeschke

Keyword(s):

Reperfusion Injury ◽

Liver Surgery ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Oxidant Stress ◽

Cellular Mechanisms ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion

Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.

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EPOR2/βcR2-independendent effects of low-dose epoetin-α in porcine liver transplantation

Bioscience Reports ◽

10.1042/bsr20171007 ◽

2017 ◽

Vol 37 (6) ◽

Cited By ~ 2

Author(s):

Linus Kebschull ◽

Leon Franz Christoph Theilmann ◽

Annika Mohr ◽

Wencke Uennigmann ◽

Sandra Stoeppeler ◽

...

Keyword(s):

Liver Transplantation ◽

Low Dose ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Porcine Liver ◽

Ischemic Time ◽

Apoptotic Effects ◽

Endothelial Nitric Oxide ◽

Porcine Liver Transplantation

Ischemia–reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/βcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2/βcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/βcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model. Landrace pigs underwent allogenic liver transplantation (follow-up: 6 h) with a portojugular shunt. Animals were divided into two groups: donor and recipient treatment with low-dose EPO (65 IU/kg) or vehicle, administered 6 h before cold perfusion and 30 min after warm reperfusion. Fourteen of 17 animals (82.4%) fulfilled the inclusion criteria. No differences were noted in operative values between the groups including hemoglobin, cold or warm ischemic time. EPO-treated animals showed a significantly lower histopathology score, reduced apoptosis, oxidative stress, and most important a significant up-regulation of endothelial nitric oxide (NO) synthase (eNOS). Donor and recipient treatment with low-dose EPO reduces the hepatic IRI via EPOR2/βcR2-independent cytoprotective mechanisms and represents a clinically applicable way to reduce IRI.

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Protective effects of ischemic postconditioning against ischemia/reperfusion injury in rats undergoing liver transplantation

World Chinese Journal of Digestology ◽

10.11569/wcjd.v18.i34.3627 ◽

2010 ◽

Vol 18 (34) ◽

pp. 3627 ◽

Cited By ~ 1

Author(s):

Han-Fei Huang ◽

Fei Song ◽

Yu-Jun Zhang ◽

Zhi-Yong Yu ◽

Jian Duan ◽

...

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Postconditioning ◽

Protective Effects

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Protective Effects of Phenylpropanoids and Phenylpropanoid-rich Essential Oils on the Cardiovascular System

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190620091915 ◽

2019 ◽

Vol 19 (17) ◽

pp. 1459-1471 ◽

Cited By ~ 1

Author(s):

Jorge M. Alves-Silva ◽

Mónica Zuzarte ◽

Carla Marques ◽

Henrique Girão ◽

Lígia Salgueiro

Keyword(s):

Cardiovascular Diseases ◽

Essential Oils ◽

Cardiovascular System ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Biological Effects ◽

Ischemia Reperfusion ◽

Future Research ◽

Protective Effects ◽

Plant Metabolites

Background: Cardiovascular diseases are the leading cause of global mortality with a tendency to increase due to population ageing as well as an increase in associated risk factors. Although current therapies improve survival rates, they are associated with several side effects, thus justifying the development of novel preventive and/or therapeutic approaches. In this way, plant metabolites such as essential oils have emerged as promising agents due to their biological effects. Objective: Bearing in mind that several essential oils are characterized by high amounts of phenylpropanoids, which may play a crucial role in the activity of these volatile extracts, a comprehensive and systematic review focusing on the cardiovascular effects of phenylpropanoid-rich essential oils is presented. Methods: Popular search engines including PubMed, Science Direct, Scopus and Google Scholar were consulted and papers from 2000 onwards were selected. Non-volatile phenylpropanoids were not considered in this review. Results: A compilation of the current knowledge on this thematic pointed out beneficial effects for volatile phenylpropanoids namely hypotensive, vasorelaxant, antiplatelet aggregation, antidyslipidaemic and antidiabetic, as well as protective properties against ischemia/reperfusion injury and heart hypertrophy. Conclusion: A better understanding of the protective effects of phenylpropanoids on the cardiovascular system is presented, thus paving the way towards future research on plant-based therapies for cardiovascular diseases.

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Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury

Cells ◽

10.3390/cells8101131 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1131 ◽

Cited By ~ 13

Author(s):

Mónica B. Jiménez-Castro ◽

María Eugenia Cornide-Petronio ◽

Jordi Gracia-Sancho ◽

Carmen Peralta

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Therapeutic Strategies ◽

Experimental Models ◽

Inflammasome Activation ◽

Liver Ischemia

Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.

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The Connection between MicroRNAs from Visceral Adipose Tissue and Non-Alcoholic Fatty Liver Disease

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2021.1 ◽

2021 ◽

Vol 64 (1) ◽

pp. 1-7

Author(s):

Veronika Zubáňová ◽

Zuzana Červinková ◽

Otto Kučera ◽

Vladimír Palička

Keyword(s):

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

Visceral Adipose Tissue ◽

Fatty Liver Disease ◽

Translational Regulation ◽

Current Knowledge ◽

Alcoholic Fatty Liver ◽

Visceral Adipose ◽

Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most important causes of liver disease worldwide leading the foreground cause of liver transplantation. Recently miRNAs, small non-coding molecules were identified as an important player in the negative translational regulation of many protein-coding genes involved in hepatic metabolism. Visceral adipose tissue was found to take part in lipid and glucose metabolism and to release many inflammatory mediators that may contribute to progression of NAFLD from simple steatosis to Non-Alcoholic SteatoHepatitis. Since visceral adipose tissue enlargement and dysregulated levels of miRNAs were observed in patients with NAFLD, the aim of this paper is to reflect the current knowledge of the role of miRNAs released from visceral adipose tissue and NAFLD.

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