scholarly journals A modified animal model of hepatic regeneration induced by hilar bile duct ligation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Li ◽  
Yichao Chai ◽  
Pengkang Chang ◽  
Fenggang Reng ◽  
Zhao Xue ◽  
...  
Keyword(s):  
Animal Model ◽  
Bile Acid ◽  
Bile Duct ◽  
Liver Function ◽  
Liver Regeneration ◽  
Sham Group ◽  
Rabbit Model ◽  
Lateral Lobe ◽  
Duct Ligation ◽  
Acid Pathway

AbstractMechanisms of the proliferation of liver are mainly studied in animal model of liver regeneration after partial hepatectomy (PH). However, the PH model involves complex regeneration mechanisms, including hemodynamic factors, cytokines, growth factors, and metabolites. Among liver metabolites, bile acid (BA) is a key signaling molecule that regulates liver regeneration. This study aimed to establish a new type of rapid liver hyperplasia model induced mainly by bile acid pathway through hepatoenteral circulation with hilar bile duct ligation (HBDL). We first established the HBDL model by ligating the bile duct of all hepatic lobes but the right lateral lobe in rabbits and compared with the PVL model and sham operation group. Changes in the liver lobe and hemodynamics were observed. Liver function and the bile acid level were also analyzed. Then we verified the HBDL model in mice. Liver function and the levels of bile acids and cytokines were tested. The protein and mRNA levels of FXR, FGF15, CYP7A1 and FoxM1b in liver tissue were also analyzed. After hilar ligation of the biliary tract, the unligated liver lobes proliferated significantly. Compared with those in the sham group, the volume and weight of the unligated right lateral lobe of the liver in the HBDL group and the PVL group increased significantly (P < 0.05). Transient liver function impairment occurred both in the HBDL group and PVL group in the rabbit model as well as the mouse models. The bile acid levels in the HBDL groups of the rabbit model and mouse model increased significantly within first week after surgery (P < 0.05). The immunohistochemistry results confirmed the proliferation of hepatocytes in the unligated liver lobe. Compared with those in the sham group, the levels of FXR, FGF15 and FoxM1b in the HBDL group were significantly increased (P < 0.05), while the expression of CYP7A1 was inhibited. Compared with those in the HBDL group, the postoperative hemodynamic changes in the PVL group were significant (P < 0.05). The levels of IL-6 and TNF-α in the HBDL group were higher than those in the sham group. The HBDL model is simple to establish and exhibits good surgical tolerance. The model has definite proliferative effect and strong specificity of bile acid pathway. This is an ideal animal model to study the mechanism of liver regeneration through bile acid pathway.

scholarly journals Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats

1991 ◽  
Vol 280 (2) ◽  
pp. 373-377 ◽  
Author(s):  
S Dueland ◽  
J Reichen ◽  
G T Everson ◽  
R A Davis
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Liver Function ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Microsomal Cytochrome ◽  
Duct Ligation ◽  
Cytochrome P 450

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

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 Effect of bile duct ligation on bile acid composition in mouse serum and liver

2011 ◽  
Vol 32 (1) ◽  
pp. 58-69 ◽  
Author(s):  
Youcai Zhang ◽  
Ji-Young Hong ◽  
Cheryl E. Rockwell ◽  
Bryan L. Copple ◽  
Hartmut Jaeschke ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Acid Composition ◽  
Bile Duct Ligation ◽  
Mouse Serum ◽  
Duct Ligation

Plasma alkaline phosphodiesterase I in intrahepatic cholestasis induced by α-naphthylisothiocyanate in rats

1988 ◽  
Vol 75 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Julie A. Quayle ◽  
Alison Capstick ◽  
Anthony I. Morris ◽  
David Billington
Keyword(s):  
Alkaline Phosphatase ◽  
Bile Acid ◽  
Bile Duct ◽  
Intrahepatic Cholestasis ◽  
Bile Duct Ligation ◽  
Gel Filtration ◽  
Extrahepatic Cholestasis ◽  
Rat Serum ◽  
Duct Ligation ◽  
Dose Dependent

1. Administration of α-naphthylisothiocyanate (ANIT) to rats produced dose-dependent increases in plasma bile acid and bilirubin concentrations. Similar increases in plasma bile acid and bilirubin concentrations were evident in bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models. 2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S. R. Simpson, K. Rahman & D. Billington (1984) Clinical Science 67, 647–652] where, after bile duct ligation, serum alkaline phosphodiesterase I was elevated sixfold before any increase in alkaline phosphatase activity became apparent. Thus, plasma alkaline phosphodiesterase I does not offer as sensitive a marker of intrahepatic cholestasis (induced by ANIT) as it does of extrahepatic cholestasis (induced by bile duct ligation). 3. Hepatic alkaline phosphodiesterase I was unaffected by ANIT pretreatment while hepatic alkaline phosphatase was increased up to seven times. It is suggested that raised plasma alkaline phosphodiesterase I is due to regurgitation of the biliary enzyme rather than overspill of the enzyme from liver into blood. 4. Gel filtration showed that 24 h and 96 h after ANIT administration, rat serum contained a high molecular weight form of alkaline phosphodiesterase I, suggesting a different isoenzyme profile.

Inhibitory Effect of Short-Term Bile Duct Ligation on Hepatic Cytochrome P450 of Bile Acid-Depleted Rats

Pathobiology ◽  
2001 ◽  
Vol 69 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Rut M. Agüero ◽  
Cristian Favre ◽  
Emilio A. Rodriguez-Garay
Keyword(s):  
Cytochrome P450 ◽  
Bile Acid ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Inhibitory Effect ◽  
Short Term ◽  
Duct Ligation ◽  
Hepatic Cytochrome

scholarly journals Increased Phosphatase of Regenerating Liver-1 by Placental Stem Cells Promotes Hepatic Regeneration in a Bile-Duct-Ligated Rat Model

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2530
Author(s):  
Jong Ho Choi ◽  
Sohae Park ◽  
Gi Dae Kim ◽  
Jae Yeon Kim ◽  
Ji Hye Jun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bile Duct ◽  
Liver Regeneration ◽  
Rat Model ◽  
Hepatocyte Proliferation ◽  
Hepatic Regeneration ◽  
Regenerating Liver ◽  
Duct Ligation ◽  
Phosphatase Of Regenerating Liver ◽  
Proliferation Of Hepatocytes

Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

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.

Cardiac Changes in An Animal Model of Liver Disease Using Bile Duct Ligation

2001 ◽  
Vol 101 (s45) ◽  
pp. 12P-12P
Author(s):  
RJ Hunter ◽  
VB Patel ◽  
AJ Baker ◽  
PJ Richardson ◽  
VR Preedy
Keyword(s):  
Animal Model ◽  
Liver Disease ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Duct Ligation
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