Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating cholestatic liver injury in a rat model of bile duct ligation

2018 ◽  
Vol 392 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Enas S. Nabih ◽  
Omnyah A. El-kharashi
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Rat Model ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Bid-mediated apoptosis does not contribute to cholestatic liver injury following bile duct ligation

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
P Nalapareddy ◽  
S Schüngel ◽  
MP Manns ◽  
H Jaeschke ◽  
A Vogel
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

scholarly journals Cell-specific regulatory effects of CXCR2 on cholestatic liver injury

2019 ◽  
Vol 317 (6) ◽  
pp. G773-G783 ◽  
Author(s):  
Takanori Konishi ◽  
Rebecca M. Schuster ◽  
Holly S. Goetzman ◽  
Charles C. Caldwell ◽  
Alex B. Lentsch
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Liver Damage ◽  
Chemokine Receptor ◽  
Therapeutic Target ◽  
Bile Duct Ligation ◽  
Wild Type ◽  
Neutrophil Accumulation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

The CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2−/− mice were subjected BDL. CXCR2 chimeric mice were created to assess the cell-specific role of CXCR2 on liver injury after BDL. SB225002, a selective CXCR2 antagonist, was administrated intraperitoneally after BDL to investigate the potential of pharmacological inhibition. CXCR2−/− mice had significantly less liver injury than wild-type mice at 3 and 14 days after BDL. There was no difference in biliary fibrosis among groups. The chemokines CXCL1 and CXCL2 were induced around areas of necrosis and biliary structures, respectively, both areas where neutrophils accumulated after BDL. CXCR2−/− mice showed significantly less neutrophil accumulation in those injured areas. CXCR2Liver+/Myeloid+ and CXCR2Liver−/Myeloid− mice recapitulated the wild-type and CXCR2-knockout phenotypes, respectively. CXCR2Liver+/Myeloid+ mice suffered higher liver injury than CXCR2Liver+/Myeloid− and CXCR2Liver−/Myeloid+; however, only those chimeras with knockout of myeloid CXCR2 (CXCR2Liver+/Myeloid− and CXCR2Liver−/Myeloid−) showed reduction of neutrophil accumulation around areas of necrosis. Daily administration of SB225002 starting after 3 days of BDL reduced established liver injury at 6 days. In conclusion, neutrophil CXCR2 guides the cell to the site of injury, while CXCR2 on liver cells affects liver damage independent of neutrophil accumulation. CXCR2 appears to be a viable therapeutic target for cholestatic liver injury. NEW & NOTEWORTHY This study is the first to reveal cell-specific roles of the chemokine receptor CXCR2 in cholestatic liver injury caused by bile duct ligation. CXCR2 on neutrophils facilitates neutrophil recruitment to the liver, while CXCR2 on liver cells contributes to liver damage independent of neutrophils. CXCR2 may represent a viable therapeutic target for cholestatic liver injury.

scholarly journals C/EBP homologous protein-induced loss of intestinal epithelial stemness contributes to bile duct ligation-induced cholestatic liver injury in mice

Hepatology ◽  
2018 ◽  
Vol 67 (4) ◽  
pp. 1441-1457 ◽  
Author(s):  
Runping Liu ◽  
Xiaojiaoyang Li ◽  
Zhiming Huang ◽  
Derrick Zhao ◽  
Bhagyalaxmi Sukka Ganesh ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Intestinal Epithelial ◽  
Homologous Protein ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Su1247 FXR AGONIST TROPIFEXOR AMELIORATES CHOLESTATIC LIVER INJURY IN A NEONATAL PIGLET MODEL OF BILE DUCT LIGATION

2020 ◽  
Vol 158 (6) ◽  
pp. S-556-S-557
Author(s):  
YONGTAO XIAO ◽  
YANG LIU ◽  
XINBEI TIAN ◽  
WEI CAI
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Neonatal Piglet ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Cholestatic liver injury model of bile duct ligation and the protection of Huang-Lian-Jie-Du decoction by NMR metabolomic profiling

RSC Advances ◽  
2015 ◽  
Vol 5 (81) ◽  
pp. 66200-66211 ◽  
Author(s):  
Dandan Wei ◽  
Shanting Liao ◽  
Junsong Wang ◽  
Minghua Yang ◽  
Lingyi Kong
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Treatment Effects ◽  
Bile Duct Ligation ◽  
Metabolomic Profiling ◽  
Injury Model ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Bile duct ligation (BDL) induced cholestasis in rats and the treatment effects of Huang-Lian-Jie-Du decoction (HLJDD) were investigated by NMR-based metabolomics approach: biphasic feature of BDL model and bilateral adjustment of HLJDD were found.

Deteriorating effect of fluvastatin on the cholestatic liver injury induced by bile duct ligation in rats

2011 ◽  
Vol 30 (1) ◽  
pp. 66-74 ◽  
Author(s):  
H. Lotková ◽  
P. Staňková ◽  
T. Roušar ◽  
O. Kučera ◽  
L. Kohoutek ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

scholarly journals Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation

2018 ◽  
Vol 314 (3) ◽  
pp. G319-G333 ◽  
Author(s):  
Nadine Gehrke ◽  
Michael Nagel ◽  
Beate K. Straub ◽  
Marcus A. Wörns ◽  
Marcus Schuchmann ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Ex Vivo ◽  
Mapk Signaling ◽  
Caspase 8 ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP−/−) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1β, CCL2, CXCL1, and CXCL2), an increased presence of CD68+ macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP−/− mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP−/− mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological options in these indications.

1025 Ursolic Acid Ameliorates Cholestatic Liver Injury Caused by Bile Duct Ligation in the Rat

2012 ◽  
Vol 142 (5) ◽  
pp. S-942
Author(s):  
Kenichi Ikejima ◽  
Kumiko Arai ◽  
Kazuyoshi Kon ◽  
Shunhei Yamashina ◽  
Sumio Watanabe
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Ursolic Acid ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Cholestatic Liver Injury
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