scholarly journals Carvedilol Attenuates the Progression of Hepatic Fibrosis Induced by Bile Duct Ligation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaopeng Tian ◽  
Chunhong Zhao ◽  
Jinbo Guo ◽  
Shurui Xie ◽  
Fengrong Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Antioxidant Properties ◽  
Dependent Manner ◽  
Sod Activity ◽  
Duct Ligation ◽  
Clinical Benefits

Background.The sympathetic nervous system (SNS) is responsible for hepatic stellate cells (HSCs) activation and the accumulation of collagen that occurs in hepatic fibrogenesis. Carvedilol has been widely used for the complication of hepatic cirrhosis in the clinic. Furthermore, it has powerful antioxidant properties. We assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may further enhance its clinical benefits.Methods.Using a bile duct ligation rat model of hepatic fibrosis, we studied the effects of carvedilol on the fibrosis, collagen deposition, and oxidative stress based on histology, immunohistochemistry, western blot, and RT-PCR analyses.Results.Carvedilol attenuated liver fibrosis, as evidenced by reduced hydroxyproline content and the accumulation of collagen, downregulated TIMP-1 and TIMP-2, and upregulated MMP-13. MMP-2 was an exception, which was decreased after carvedilol treatment for 2 weeks and upregulated after carvedilol treatment for 4 weeks. Carvedilol reduced the activation of HSCs, decreased the induction of collagen, transforming growth factor-β1, and MDA content, and strengthened the SOD activity. The antifibrotic effects were augmented as dosages increased.Conclusions.The study indicates that carvedilol attenuated hepatic fibrosis in a dose-dependent manner. It can decrease collagen accumulation and HSCs activation by the amelioration of oxidative stress.

scholarly journals Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4181
Author(s):  
Zi-Yu Chang ◽  
Chin-Chang Chen ◽  
Hsuan-Miao Liu ◽  
Yuan-Chieh Yeh ◽  
Tung-Yi Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Matrix Metalloproteinase 2 ◽  
Positive Effects ◽  
Duct Ligation

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-β, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.

scholarly journals MicroRNA-29a Alleviates Bile Duct Ligation Exacerbation of Hepatic Fibrosis in Mice through Epigenetic Control of Methyltransferases

2017 ◽  
Vol 18 (1) ◽  
pp. 192 ◽  
Author(s):  
Ya-Ling Yang ◽  
Feng-Sheng Wang ◽  
Sung-Chou Li ◽  
Mao-Meng Tiao ◽  
Ying-Hsien Huang
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Epigenetic Control ◽  
Duct Ligation

Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats

2003 ◽  
Vol 285 (5) ◽  
pp. G1004-G1013 ◽  
Author(s):  
Zhi Zhong ◽  
Matthias Froh ◽  
Mark Lehnert ◽  
Robert Schoonhoven ◽  
Liu Yang ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Control Diet ◽  
Free Radical Scavengers ◽  
Bile Duct Proliferation ◽  
Duct Ligation ◽  
Experimental Cholestasis

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-α1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of α-smooth muscle actin and transforming growth factor-β and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.

scholarly journals Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in rats

2008 ◽  
Vol 38 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Kazunori Maeda ◽  
Masahiko Koda ◽  
Tomomitsu Matono ◽  
Takaaki Sugihara ◽  
Satoru Yamamoto ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Preventive Effects

scholarly journals CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

2015 ◽  
Vol 52 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Keli Cristina Simões da SILVEIRA ◽  
Cassiana Macagnan VIAU ◽  
Josiane Raskopf COLARES ◽  
Jenifer SAFFI ◽  
Norma Possa MARRONI ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Membrane Potential ◽  
Bile Duct ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Bile Duct Ligation ◽  
Decompensated Cirrhosis ◽  
Biliary Cirrhosis ◽  
Duct Ligation

Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

scholarly journals Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

2019 ◽  
Vol 22 ◽  
pp. 301-312 ◽  
Author(s):  
Michael D Hambuchen ◽  
Michael D Berquist ◽  
Christy M Simecka ◽  
Mitchell R McGill ◽  
Melinda G Gunnell ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Bile Duct ◽  
Liver Dysfunction ◽  
Hepatic Dysfunction ◽  
Bile Duct Ligation ◽  
Dependent Manner ◽  
Duct Ligation ◽  
Male Wistar Rats ◽  
Experimental Treatments ◽  
Altered Liver

Purpose: Methamphetamine (METH) abuse is associated with hepatic dysfunction related comorbidities such as HIV, hepatitis C, and polysubstance abuse with acetaminophen-containing opioid formulations. We aimed to develop a bile duct ligation (BDL)-induced hepatic dysfunction model for studying both METH and experimental treatments for METH abuse in this comorbidity. Methods: Sham or BDL surgery was performed in male Wistar rats on day 0. Liver function was measured throughout the study. On days 7 and 19, serum pharmacokinetics studies were performed with 1 mg/kg subcutaneous (sc) METH. On day 21, this dose was repeated to determine 2 h post-METH brain concentrations. METH-induced open field behaviors were measured every other day (days 12 - 16) with ascending sc doses (0.3 – 3 mg/kg). Results: BDL transiently increased alanine aminotransferase levels and altered liver structure, which resulted in significantly greater METH serum and brain exposure. In the BDL compared to sham group, there was a longer duration of METH-induced locomotor activity (after 1 and 3 mg/kg) and stereotypy (after 3 mg/kg). Conclusions: In rats, liver dysfunction reduced METH clearance, increased brain METH concentrations, and enhanced METH effects on locomotor activity in a dose dependent manner. In addition, this model could be further developed to simulate the associated hepatic dysfunction of key METH abuse comorbidities for preclinical testing of novel pharmacotherapies for effectiveness and/or toxicity in vulnerable populations.

Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation

1999 ◽  
Vol 96 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Paula MAYORAL ◽  
Manuela CRIADO ◽  
Froilan HIDALGO ◽  
Olga FLORES ◽  
Miguel A. ARÉVALO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Nitric Oxide Synthase ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Western Blots ◽  
Circulatory Effects ◽  
Duct Ligation ◽  
Oxide Synthase

Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects.

[335] THE ANTI-FIBROTIC EFFECTS OF CELECOXIB IN BILE DUCT LIGATION- AND THIOACETAMIDE-INDUCED HEPATIC FIBROSIS MODELS IN RAT

2007 ◽  
Vol 46 ◽  
pp. S131
Author(s):  
Y.H. Paik ◽  
S.H. Kang ◽  
H.J. Lee ◽  
S.H. Ahn ◽  
K.H. Han ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats

2010 ◽  
Vol 112 (3) ◽  
pp. 259-269 ◽  
Author(s):  
Burhan Aksu ◽  
Hasan Umit ◽  
Mehmet Kanter ◽  
Ahmet Guzel ◽  
Cevat Aktas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methylene Blue ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Hepatic Damage ◽  
Duct Ligation
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