scholarly journals AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats

2019 ◽  
Vol 7 (6) ◽  
pp. 925-936
Author(s):  
Hesham M. Mahmoud ◽  
Mona Osman ◽  
Osama Elshabrawy ◽  
Heba M. I. Abdallah ◽  
Ahmed Khairallah
Keyword(s):  
Lipid Peroxidation ◽  
Bile Duct ◽  
Liver Injury ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Bile Duct Ligation ◽  
Receptor Activation ◽  
Cb2 Receptor ◽  
Duct Ligation ◽  
Cb2 Receptors

BACKGROUND: The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury. AIM: In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury. METHODS: Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed. RESULTS: Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers. CONCLUSION: In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

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 Vitamin A Supplementation Alleviates Extrahepatic Cholestasis Liver Injury through Nrf2 Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Guiyang Wang ◽  
Peng Xiu ◽  
Fu Li ◽  
Cheng Xin ◽  
Kewei Li
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Liver Function ◽  
Vitamin A ◽  
Western Blotting ◽  
Bile Duct Ligation ◽  
Retinyl Palmitate ◽  
Binding Activity ◽  
Extrahepatic Cholestasis ◽  
Duct Ligation

Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

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

scholarly journals Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

10.3791/52438 ◽  
2015 ◽  
Author(s):  
Carmen G. Tag ◽  
Sibille Sauer-Lehnen ◽  
Sabine Weiskirchen ◽  
Erawan Borkham-Kamphorst ◽  
René H. Tolba ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Obstructive Cholestasis

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.

scholarly journals Ascorbate lacks significant influence in rats with bile duct ligation-induced liver injury

2017 ◽  
Vol 80 (9) ◽  
pp. 539-550 ◽  
Author(s):  
Hsin-Ling Ho ◽  
Teh-Ia Huo ◽  
Ting Chang ◽  
Wen-Shin Lee ◽  
I-Fang Hsin ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Significant Influence ◽  
Bile Duct Ligation ◽  
Duct Ligation
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