scholarly journals Early use of dexamethasone increases Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent manner

2020 ◽  
Vol 21 (9) ◽  
pp. 727-739
Author(s):  
Jing-wen Deng ◽  
Qin Yang ◽  
Xiao-peng Cai ◽  
Jia-ming Zhou ◽  
Wei-gao E ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Kupffer Cells ◽  
Dependent Manner ◽  
Early Use

scholarly journals The Ugly Side of Colchicine

2021 ◽  
Vol 9 ◽  
pp. 232470962110297
Author(s):  
Justin Cozza ◽  
Tuong Vi Cassandra Do ◽  
Shyam Ganti ◽  
Jayaramakrishna Depa
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Activated Charcoal ◽  
The United States ◽  
Multiple Organ ◽  
Poison Control ◽  
Fab Fragments ◽  
Early Use ◽  
Potential Use ◽  
Electrolyte Abnormalities

We report a rare case of a 32-year-old male who ingested 32.4 to 54 mg of colchicine and presented after 44 hours. He developed progressive multiple organ failure with shock, acute kidney failure, troponemia, pancytopenia, absolute neutropenia, disseminated intravascular coagulation, acute liver failure, rhabdomyolysis, and lactic acidosis. He also developed electrolyte abnormalities and refractory hypoglycemia. Initial treatment consisted of activated charcoal, fluids, and broad-spectrum antibiotics with supportive treatment of mechanical ventilation, hemodialysis, vasopressors, N-acetylcysteine, colony-stimulating factors, and blood products. Literature shows potential benefit of colchicine-specific Fab fragments for acute toxicity with limited studies and is not currently available in the United States. Further research for N-acetylcysteine protocol for acute liver failure in colchicine toxicity and potential use of colchicine-specific Fab fragments is needed. Our case demonstrates the importance of early use of activated charcoal for ingestion overdose with the incorporation of poison control into multidisciplinary team for coordinated patient care.

scholarly journals Role of Kupffer cells and toll-like receptor 4 in acetaminophen-induced acute liver failure

2013 ◽  
Vol 180 (1) ◽  
pp. 147-155 ◽  
Author(s):  
James E. Fisher ◽  
Travis J. McKenzie ◽  
Joseph B. Lillegard ◽  
Yue Yu ◽  
Justin E. Juskewitch ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Kupffer Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

Epiregulin promotes the emergence and proliferation of adult liver progenitor cells

2014 ◽  
Vol 307 (1) ◽  
pp. G50-G57 ◽  
Author(s):  
Kyoko Tomita ◽  
Hiroaki Haga ◽  
Kei Mizuno ◽  
Tomohiro Katsumi ◽  
Chikako Sato ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Serum Levels ◽  
Dependent Manner ◽  
Portal Area ◽  
Injury Model

We have previously reported that epiregulin is a growth factor that seems to act on liver progenitor cells (LPCs) during liver regeneration. However, the relationship between epiregulin and LPCs has remained unclear. The aim of the present study was to clarify the role of epiregulin during liver regeneration. The serum levels of epiregulin in patients with acute liver failure were examined. A liver injury model was developed using mice fed a diet containing 0.1% 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) to induce LPCs. We then evaluated the expression of epiregulin and LPCs in these mice. The proliferation of epithelial cell adhesion molecule + LPCs cultured with epiregulin was examined in vitro, and finally epiregulin was overexpressed in mouse liver. In patients with acute liver failure, serum epiregulin levels were elevated significantly. In DDC mice, LPCs emerged around the portal area. Epiregulin was also detected around the portal area during the course of DDC-induced liver injury and was partially coexpressed with Thy1. Serum epiregulin levels in DDC mice were also significantly elevated. Recombinant epiregulin augmented the proliferative capacity of the LPCs in a dose-dependent manner. In mice showing overexpression of epiregulin, the expression of PCNA on hepatocytes was increased significantly. Finally, LPCs emerged around the portal area after epiregulin gene delivery. We concluded that epiregulin promotes the proliferation of LPCs and DNA synthesis by hepatocytes and is upregulated in the serum of patients with liver injury. Furthermore, induction of epiregulin leads to the appearance of LPCs. Epiregulin would be a useful biomarker of liver regeneration.

rhIL-1Ra reduces hepatocellular apoptosis in mice with acute liver failure mainly by inhibiting the activities of Kupffer cells

2019 ◽  
Vol 854 ◽  
pp. 338-346 ◽  
Author(s):  
Xiaolan Yu ◽  
Liang Zhou ◽  
Qing Deng ◽  
Xiaoyue Chen ◽  
Quanhui Tan ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Kupffer Cells ◽  
Hepatocellular Apoptosis

scholarly journals Liver injury mediated by the UII and its receptor (UT) system is possibly associated with the activation of autophagy-related and apoptosis-resisted pathways of Kupffer cells in acute liver failure

2021 ◽  
Vol 19 ◽  
pp. 205873922110274
Author(s):  
Huan Zhong ◽  
Yu He ◽  
Xue Yang ◽  
Qin-Qin Si ◽  
Pin Xie ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Kupffer Cells ◽  
Caspase 3 ◽  
Innate Immune ◽  
Urotensin Ii ◽  
Proapoptotic Protein ◽  
Specific Antagonist ◽  
Autophagy Inhibition

The system of urotensin II (UII) and its receptor (UT) (or: UII/UT system) mediates hepatic immune inflamed injury in acute liver failure (ALF) with autophagy inhibition. However, it is unknown whether the system has an effect on liver autophagy in ALF. In this study, we attempted to explore hepatic autophagy response in ALF through blocking the UII/UT signal. Autophagy-related genes were examined in the liver tissues of lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced ALF after pretreatment of UT receptor specific antagonist urantide. And then, the levels of autophagy- and apoptosis-related genes were assayed in LPS-stimulated KCs via urantide pretreatment. We found that the expressions of hepatic autophagy related genes, including Beclin-1, Atg5, Atg7, LC3 and p62 mRNA, and LC3 II and p62 protein, were significantly downregulated in LPS/D-GalN-induced ALF mice; but they were not affected by pretreatment of urantide, a special UT receptor antagonist. To probe inflammatory mechanisms of the UII/UT system, we further investigated the effect of the system on Kupffer cells (KCs), the innate immune cells in liver. We found that urantide pretreatment significantly inhibited production of inflammatory injury molecules including TRAF6 and ROS in LPS-stimulated KCs. LPS stimulation induced LC3 and p62 mRNA and LC3 II and p62 protein expression in KCs. After urantide pretreatment, LC3 and p62 mRNA and LC3 II protein were downregulated, while p62 protein was upregulated in LPS-stimulated KCs. In addition, antiapoptotic protein Bcl-2 inhibition and proapoptotic protein cleaved caspase-3 increase were observed in LPS-stimulated KCs, and the effects were enhanced after urantide pretreatment in the study. We conclude that liver injury mediated by the UII/UT system is possibly associated with the activation of autophagy-related and apoptosis-resisted pathways of KCs in ALF.

scholarly journals Noncanonical Wnt5a/JNK Signaling Contributes to the Development of D-Gal/LPS-Induced Acute Liver Failure

2021 ◽  
Author(s):  
Xiang-fen Ji ◽  
Yu-chen Fan ◽  
Fei Sun ◽  
Jing-wei Wang ◽  
kai wang
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Inflammatory Cytokines ◽  
Dependent Manner ◽  
Jnk Signaling ◽  
Wnt5a Expression ◽  
Jnk Activation

Abstract Acute liver failure (ALF) is a deadly clinical disorder with few effective treatments and unclear pathogenesis. In our previous study, we demonstrated that aberrant Wnt5a expression was involved in acute on chronic liver failure. However, the role of Wnt5a in ALF is unknown. We investigated the expression of Wnt5a and its downstream signaling of c-jun N-terminal kinase (JNK) in a mouse model of ALF established by co-injection of D-galactosamine (D-Gal) and lipopolysaccharide (LPS) in C57BL/6 mice. We also investigated the role of Box5, a Wnt5a antagonist in vivo. Moreover, the effect of Wnt5a/JNK signaling on downstream inflammatory cytokines expression, phagocytosis and migration in THP-1 macrophages was studied in vitro. Aberrant Wnt5a expression and JNK activation were detected in D-Gal/LPS-induced ALF mice. Box5 pretreatment reversed JNK activation, and eventually decreased the mortality rate of D-Gal/LPS-treated mice with reduced hepatic necrosis and apoptosis, serum ALT and AST levels, and liver inflammatory cytokines expression, although the last was not significant. We further demonstrated that recombined Wnt5a (rWnt5a) induced tumor necrosis α (TNF-α) and Interleukin-6 (IL-6) mRNA expression, and increased the phagocytosis ability of THP-1 macrophages in a JNK-dependent manner, which could be restored by Box5. In addition, rWnt5a-induced migration of THP-1 macrophages was also turned by Box5. Our findings suggested that Wnt5a/JNK signaling play important role in the development of ALF, and Box5 could have particular hepatoprotecive effects in ALF.

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