scholarly journals Role of the Gut–Liver Axis in Driving Parenteral Nutrition-Associated Injury

Children ◽  
2018 ◽  
Vol 5 (10) ◽  
pp. 136 ◽  
Author(s):  
Christine Denton ◽  
Amber Price ◽  
Julie Friend ◽  
Chandrashekhara Manithody ◽  
Keith Blomenkamp ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Parenteral Nutrition ◽  
Current Knowledge ◽  
Significant Risk ◽  
Associated Injury ◽  
Gut Function ◽  
Enteral Feedings ◽  
Cholestatic Liver Injury

For decades, parenteral nutrition (PN) has been a successful method for intravenous delivery of nutrition and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. Although the benefits of PN are evident, its use does not come without a significant risk of complications. For instance, parenteral nutrition-associated liver disease (PNALD)—a well-described cholestatic liver injury—and atrophic changes in the gut have both been described in patients receiving PN. Although several mechanisms for these changes have been postulated, data have revealed that the introduction of enteral nutrition may mitigate this injury. This observation has led to the hypothesis that gut-derived signals, originating in response to the presence of luminal contents, may contribute to a decrease in damage to the liver and gut. This review seeks to present the current knowledge regarding the modulation of what is known as the “gut–liver axis” and the gut-derived signals which play a role in PN-associated injury.

scholarly journals Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

2021 ◽  
Vol 22 (14) ◽  
pp. 7249
Author(s):  
Siyer Roohani ◽  
Frank Tacke
Keyword(s):  
Bone Marrow ◽  
Liver Injury ◽  
Current Knowledge ◽  
Hepatocellular Cancer ◽  
Complete Recovery ◽  
Hepatic Macrophages ◽  
Liver Injuries ◽  
Microbial Products ◽  
Injured Liver

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.

scholarly journals The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Mechanisms Of Action ◽  
Nadph Oxidases ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

scholarly journals Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 288
Author(s):  
Julie Massart ◽  
Karima Begriche ◽  
Jessica H. Hartman ◽  
Bernard Fromenty
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Liver Disease ◽  
Fatty Liver ◽  
Current Knowledge ◽  
Physiological Role ◽  
Experimental Investigations ◽  
Rat Liver Mitochondria ◽  
Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

scholarly journals Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qingfei Chu ◽  
Xinyu Gu ◽  
Qiuxian Zheng ◽  
Jing Wang ◽  
Haihong Zhu
Keyword(s):  
Cell Death ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Cellular Energetics ◽  
Liver Cell Death

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

scholarly journals Cholestatic liver injury induced by food additives, dietary supplements and parenteral nutrition

2020 ◽  
Vol 136 ◽  
pp. 105422 ◽  
Author(s):  
Vânia Vilas-Boas ◽  
Eva Gijbels ◽  
Joop Jonckheer ◽  
Elisabeth De Waele ◽  
Mathieu Vinken
Keyword(s):  
Liver Injury ◽  
Parenteral Nutrition ◽  
Dietary Supplements ◽  
Food Additives ◽  
Cholestatic Liver Injury

scholarly journals Treatment of Parenteral Nutrition-Associated Liver Disease: The Role of Lipid Emulsions

2013 ◽  
Vol 4 (6) ◽  
pp. 711-717 ◽  
Author(s):  
Prathima Nandivada ◽  
Sarah J. Carlson ◽  
Melissa I. Chang ◽  
Eileen Cowan ◽  
Kathleen M. Gura ◽  
...  
Keyword(s):  
Liver Disease ◽  
Parenteral Nutrition ◽  
Lipid Emulsions

scholarly journals Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2219-2227 ◽  
Author(s):  
Nan Wu ◽  
Leonardo Baiocchi ◽  
Tianhao Zhou ◽  
Lindsey Kennedy ◽  
Ludovica Ceci ◽  
...  
Keyword(s):  
Liver Injury ◽  
Functional Role ◽  
Receptor Signaling ◽  
Secretin Receptor ◽  
Cholestatic Liver Injury

Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP

2012 ◽  
Vol 303 (4) ◽  
pp. G498-G506 ◽  
Author(s):  
Jörn M. Schattenberg ◽  
Michael Nagel ◽  
Yong Ook Kim ◽  
Tobias Kohl ◽  
Marcus A. Wörns ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Hepatocellular Injury ◽  
Inhibitory Protein ◽  
Hepatocellular Apoptosis ◽  
Specific Deletion

Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts promotes hepatic fibrosis and the progression to cirrhosis with deleterious effects on liver physiology. The role of apoptosis signaling pathways in the development of fibrosis remains undefined. The aim of the current study was to determine the involvement of the caspase-8 homologue cellular FLICE-inhibitory protein (cFLIP) during the initiation and progression of fibrosis. Liver injury and fibrosis from carbon tetrachloride (CCl4) and thioacetamide (TAA) were examined in mice exhibiting a hepatocyte-specific deletion of cFLIP ( flip −/−). Acute liver injury from CCl4 and TAA were enhanced in flip −/− mice. This was accompanied by increased activation of caspase-3 and -9, pronounced phosphorylation of JNK, and decreased phosphorylation of Erk. Deletion of the cJun NH2-terminal kinase 2 (JNK2) in flip −/− mice protected from injury. Hepatic fibrosis was increased at baseline in 12-wk-old flip −/− mice, and progression of fibrosis from TAA was accelerated compared with the wild type. In conclusion, deletion of cFLIP in hepatocytes leads to increased fibrosis and accelerated fibrosis progression. This is accompanied by increased injury involving the activation of caspases and JNK2. Thus predisposition to liver injury involving increased hepatocellular apoptosis is a critical mediator of accelerated fibrogenesis, and prevention of liver injury will be a most important measure for patients with chronic liver disease.

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