Protective effects of SRT1720 via the HNF1α/FXR signalling pathway and anti-inflammatory mechanisms in mice with estrogen-induced cholestatic liver injury

2016 ◽  
Vol 264 ◽  
pp. 1-11 ◽  
Author(s):  
Linxi Yu ◽  
Xiaoxin Liu ◽  
Xiaojiaoyang Li ◽  
Zihang Yuan ◽  
Hang Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signalling Pathway ◽  
Protective Effects ◽  
Anti Inflammatory ◽  
Cholestatic Liver Injury

scholarly journals Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-κB Signaling Pathway Inhibition in Bile Duct-Ligated Mice

2018 ◽  
Vol 49 (3) ◽  
pp. 1124-1137 ◽  
Author(s):  
Zhiyong Weng ◽  
Yue Chi ◽  
Jing Xie ◽  
Xuefeng Liu ◽  
Jiehua Hu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Inflammatory Responses ◽  
Protective Effects ◽  
Bile Duct Proliferation ◽  
Duct Ligation ◽  
Anti Inflammatory ◽  
Cholestatic Liver Injury ◽  
Lps Binding

Background/Aims: Clinically, biliary obstruction is often accompanied by progressive inflammation. Dehydroandrographolide (DA) possesses anti-inflammatory properties. However, the anti-inflammatory activities of DA in cholestatic liver injury remain unclear. Methods: Mice were administered with DA by intraperitoneal injection after bile duct ligation (BDL) on day 1. Then mice were subjected to an ileocecal vein injection of lipopolysaccharide (LPS). Liver function markers, histology, pro-inflammatory cytokine levels, NF-κB activation and fibrosis formation were evaluated in BDL mice with LPS. LPS binding to primary Kupffer cells was examined by high-content cytometers. Results: DA was shown to greatly lower initially higher than normal levels of alanine aminotransferase (ALT) and total bilirubin (TBIL) in the serum and liver of BDL mice with LPS. DA exerted hepatic protective effects that were also confirmed by prolonged survival of BDL mice with LPS. Liver histopathology showed reduced inflammatory cellular infiltration, bile duct proliferation, and biliary necrosis with DA treatment. Furthermore, DA reduced the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in liver tissue and plasma and showed decreased NF-κB activation in BDL mice with LPS. DA could prevent LPS binding to primary Kupffer cells in the normal liver and BDL mice liver. DA also suppressed LPS-stimulated inflammatory responses by blocking the interaction between LPS and TLR4 in primary Kupffer cells and human LX-2 cells, thereby inhibiting NF-κB activation. Conclusion: DA inhibition of inflammation against liver damage following BDL with LPS may be a promising agent for the treatment of cholestatic liver injury.

scholarly journals Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2509 ◽  
Author(s):  
Jing Zhang ◽  
Xin Guo ◽  
Taiji Hamada ◽  
Seiya Yokoyama ◽  
Yuka Nakamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Critical Role ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Fibrotic Liver ◽  
Intrahepatic Bile Ducts ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

scholarly journals Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2/HO-1/NQO1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Feng ◽  
Ruixia Cui ◽  
Zeyu Li ◽  
Xia Zhang ◽  
Yifan Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Hepatic Injury ◽  
Protective Effects ◽  
Serum Aminotransferase ◽  
Anti Inflammatory

Acetaminophen- (APAP-) induced hepatic injury is an important clinical challenge. Oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress (ERS) contribute to the pathogenesis. Methane has potential anti-inflammatory, antioxidant, and antiapoptotic properties. This project was aimed at studying the protective effects and relative mechanisms of methane in APAP-induced liver injury. In the in vivo experiment, C57BL/6 mice were treated with APAP (400 mg/kg) to induce hepatic injury followed by methane-rich saline (MRS) 10 ml/kg i.p. after 12 and 24 h. We observed that MRS alleviated the histopathological lesions in the liver, decreased serum aminotransferase levels, reduced the levels of inflammatory cytokines, suppressed the nuclear factor-κB expression. Further, we found that MRS relieved oxidative stress by regulating the Nrf2/HO-1/NQO1 signaling pathway and their downstream products after APAP challenge. MRS also regulated proteins associated with ERS-induced apoptosis. In the in vitro experiment, the L-02 cell line was treated with APAP (10 mM) to induce hepatic injury. We found that a methane-rich medium decreased the levels of reactive oxygen species (DHE fluorescent staining), inhibited apoptosis (cell flow test), and regulated the Nrf2/HO-1/NQO1 signaling pathway. Our data indicated that MRS prevented APAP-induced hepatic injury via anti-inflammatory, antioxidant, anti-ERS, and antiapoptotic properties involving the Nrf2/HO-1/NQO1 signaling pathway.

scholarly journals Resveratrol and Montelukast Alleviate Paraquat-Induced Hepatic Injury in Mice: Modulation of Oxidative Stress, Inflammation, and Apoptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Noha A. El-Boghdady ◽  
Nourtan F. Abdeltawab ◽  
Mohammed M. Nooh
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Antioxidant Properties ◽  
Protective Effects ◽  
Serum Total Protein ◽  
Stress Markers ◽  
Group I ◽  
Radical Generation ◽  
Anti Inflammatory ◽  
Induced Apoptosis

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF-α levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of p53, Bax, and Bcl-2. Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.

scholarly journals Protective Effects of Guava Pulp on Cholestatic Liver Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jian Peng ◽  
Chunyan Yue ◽  
Kai Qiu ◽  
Jie Chen ◽  
Maria-Angeles Aller ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Protective Effects ◽  
Western Blots ◽  
Duct Ligation ◽  
Stress Changes ◽  
Liver Fibrogenesis ◽  
Brdu Assay ◽  
Cholestatic Liver Injury

Background. Cholestatic liver injury is a leading cause of chronic liver diseases involved with oxidative stress changes and inflammation; thus, antioxidant and anti-inflammation compound-rich guava may play a pivotal role in protecting against the cholestatic liver damages. Our aims for this study are to determine whether guava pulp (GP) has protective effects on cholestatic liver injury-induced mouse model and on interleukin-6 (IL-6) mediated proliferation of QBC939 cholangiocarcinoma cell line. Methods. Mice were induced to cholestatic liver damage by left and median bile duct ligation (LMBDL) surgery and then treated with GP. Plasma and liver samples were collected for biochemical and pathological assays. 5-Bromo-2′-deoxyuridine (BrdU) assay and Western blots were used to detect proliferation and gene expression in QBC939 cells, respectively. Results. Compared with LMBDL only group, in GP-treated mice, the levels of alanine aminotransferase (ALT) and bilirubin decreased, biliary epithelial cell proliferation and liver fibrogenesis were suppressed, Src/MEK/ERK1/2/c-Myc pathway and expressions of transforming growth factor β1(TGF-β1), tissue inhibitor of metalloproteinases TIMP), and procollagen 1α1(COL1α1) were downregulated significantly. Moreover, the GP extract reduced IL-6-enhanced QBC939 cell proliferation, p-ERK, and c-Myc expression as well. Conclusions. GP may provide a new perspective for the treatment of cholestatic liver injury.

Velvet antler polypeptide prevents the disruption of hepatic tight junctions via inhibiting oxidative stress in cholestatic mice and liver cell lines

2020 ◽  
Vol 11 (11) ◽  
pp. 9752-9763
Author(s):  
Lihua Li ◽  
Fan Yang ◽  
Rongjun Jia ◽  
Pengfei Yan ◽  
Liman Ma
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Tight Junctions ◽  
Cell Lines ◽  
Liver Cell ◽  
Lithocholic Acid ◽  
Protective Effects ◽  
Velvet Antler ◽  
Velvet Antler Polypeptide ◽  
Cholestatic Liver Injury

The present study aims to examine the protective effects and mechanism of a velvet antler polypeptide (VAP) against lithocholic acid (LCA)-induced cholestatic liver injury in mice.

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