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 Shenqi Fuzheng Injection impairs bile duct ligation-induced cholestatic liver injury in vivo

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Fei Cao ◽  
Peng Liu ◽  
Xianbin Zhang ◽  
Yanfen Hu ◽  
Xin Dong ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Injury ◽  
Protective Function ◽  
Ppar Γ ◽  
Duct Ligation ◽  
Shenqi Fuzheng Injection ◽  
Cox 2 ◽  
Factor Α ◽  
Cholestatic Liver Injury

Abstract Background and aim: The aim of the present study sought to determine the protective function of Shenqi Fuzheng Injection (SFI) in cholestatic liver injury. Methods: Cholestatic liver injury was induced in a 7-day bile duct-ligated (BDL) rat model. Rats were divided into three groups that were comprised of: (1) Sham; (2) BDL model; and (3) SFI treatment. The sham and BDL groups were treated with an appropriate volume of 0.9% sodium chloride as the vehicle, and the SFI group was administered SFI at a dose of 20 ml/kg/day, via tail vein injection. Results: SFI significantly (all at P<0.01) decreased the levels of serum aspartate aminotransferase and alanine aminotransferase as compared with the BDL group, which was associated with reduced severity of inflammatory cell infiltration and hepatic damage. Moreover, SFI significantly decreased the levels of hepatic interleukin-6 (P<0.01), tumor necrosis factor-α (P=0.041), and malondialdehyde (P=0.026), and significantly increased the levels of total superoxide dismutase (P<0.01), and the GSH/GSSG ratio (P=0.041) in the liver. Western blot analysis showed that SFI increased PPAR-γ expression; however, SFI treatment decreased cyclooxygenase-2 (COX-2) expression and the phosphorylation of NF-κBp65. Conclusions: These data demonstrated that SFI attenuated both inflammation and oxidative stress, and disrupted cholestatic liver injury. The involved mechanism was dependent, at least in part, on regulating PPAR-γ, COX-2, and NF-κBp65 expression.

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.

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.

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.

scholarly journals Protective effects of PAMAM dendrimers against ANIT-induced cholestatic liver injury in mice

2020 ◽  
Author(s):  
Chuang Zhang ◽  
Xuelai Liu ◽  
Weirui Ren ◽  
Shaojie Liu ◽  
Xiangjian Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Functional Expression ◽  
Pamam Dendrimer ◽  
Pamam Dendrimers ◽  
Common Disease ◽  
Protective Effects ◽  
Tnf Α ◽  
Cholestatic Liver Injury

Abstract Background:Cholestatic liver disease (CLD) is a common disease of infancy, threatening infants’ health seriously. However, there is no effective drug to treat this disease.It is urgently to develop a new drug to overcome it. Polyamide-amine (PAMAM) dendrimer is a hyperbranched nano polymer, which has been found that has an anti-inflammatory effect recently. For this study, we aim to explore the protective effect and mechanism of PAMAM on CLD.Methods:In this study, a mouse model of cholestatic liver injury was created using ANIT,and TNF-α was utilized to stimulate human hepatocytes to investigate the protective effect and mechanism of 4.5th generation carboxyl-terminated PAMAM dendrimers (G4.5-COOH) in vivo and in vitro.Liver serum biochemistry, inflammatory, oxidative stress(OxS), endoplasmic reticulum(ER) stress and apoptosis indicators were determined.In addition, the effects of G4.5-COOH on PPAR-γ and PI3K/AKT/mTOR signaling pathway were studied. Data were analyzed by using one-way ANOVA. Results:We find the G4.5-COOH may inhibit TNF-α to damage hepatocytes and ameliorate the cholestatic liver injury. We also find that the protective effect of G4.5-COOH might be due to inhibition of P-Akt、P-mTOR expression by a mechanism that might be partly dependent on up-regulated functional expression of PPAR-γ.Conclusions:G4.5-COOH PAMAM dendrimer has a protective effect on CLD.

scholarly journals Protective Effects of Salidroside against Carbon Tetrachloride (CCl4)-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice

2019 ◽  
Vol 20 (13) ◽  
pp. 3187 ◽  
Author(s):  
Shi-Yu Lin ◽  
Xu Dan ◽  
Xia-Xia Du ◽  
Chong-Lin Ran ◽  
Xu Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Protein Kinase ◽  
Liver Injury ◽  
Liver Steatosis ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Mitogen Activated Protein ◽  
And Function

The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function.

scholarly journals Hepatoprotective Activity of the Ethanolic Extract of Polygonum multiflorum Thunb. against Oxidative Stress-Induced Liver Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
En-Yuan Lin ◽  
Amarzaya Chagnaadorj ◽  
Shyh-Jer Huang ◽  
Ching-Chiung Wang ◽  
Yung-Hsiao Chiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bile Acid ◽  
Liver Injury ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Dependent Manner ◽  
Polygonum Multiflorum ◽  
In Vivo Models ◽  
Duct Ligation

Oxidative stress is an important pathological mechanism in various liver diseases. Polygonum multiflorum Thunb. (PM) can be used for the treatment of diseases associated with aging, hyperlipidemia, and oxidative stress in traditional Chinese medicine. In this study, we examined the hepatoprotective effects of the ethanolic extract of PM (PME) in in vitro and in vivo models. The PME induced expression of antioxidant-response-element- (ARE-) related genes in HepG2 cells showed a dose-dependent manner. Pretreatment of HepG2 cell with PME suppressed H2O2- and acetaminophen- (APAP-) induced cellular reactive oxygen species (ROS) generation and cytotoxicity. In APAP-induced mouse liver injury, pretreatment with PME also showed ability to increase the survival rate and reduce the severity of liver injury. Treatment with PME attenuated bile duct ligation-induced extrahepatic cholestatic liver injury and further increased multidrug resistance protein 4 (MRP4) and reduced organic anion-transporting polypeptide (OATP) expression. Furthermore, increased nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) was observed after treatment with PME in both in vivo models. In conclusion, the current study showed the hepatoprotective activity of PME by regulating the redox state in liver injury through Nrf2 activation and controlling hepatic bile acid homeostasis in obstructive cholestasis, through bile acid transporter expression modulation.

scholarly journals Paeoniflorin Protects against ANIT-Induced Cholestatic Liver Injury in Rats via the Activation of SIRT1-FXR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lisheng Chen ◽  
Shizhang Wei ◽  
Honghong Liu ◽  
Jianyu Li ◽  
Manyi Jing ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Serum Levels ◽  
Water Soluble ◽  
Bile Acid Metabolism ◽  
Protective Effects ◽  
Caspase 1 ◽  
Tnf Α ◽  
Cholestatic Liver Injury

Paeoniflorin (PF), a water-soluble monoterpene glycoside, is initially isolated from the dried roots of Paeonia lactiflora Pall., which has effects on ameliorating cholestasis in our previous study. However, comprehensive approaches for understanding the protective effects and mechanisms underlying cholestatic liver injury from the regulating of bile acid metabolism have not been sufficiently elucidated. This study was aimed to explore the effectiveness as well as potential mechanism of PF on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Rats with cholestasis induced by ANIT was used to evaluate the protective effects and mechanism of PF by regulating SIRT1/FXR and NF-κB/NLRP3 signaling pathway. Rats were intragastrically administrated with ANIT to establish cholestatic liver injury model. Serum levels of ALT, AST, TBA, TBIL, ALP, γ-GT and ALB in rats were detected. The histopathology of the liver of rats was analyzed in vivo. The relative mRNA expression and protein expression levels of IL-18, IL-1β, TNF-α, HO-1, Nrf2, TLR4, NLRP3, Caspase-1, ASC, NF-κB, FXR, and SIRT1 in liver of rats were investigated. The results showed that the serum indexes and the liver histopathology were significantly improved by PF. The overexpression of IL-18, IL-1β, TNF-α, NLRP3, ASC, and Caspase-1 in liver was markedly reduced by PF. Furthermore, PF dramatically increased the mRNA and protein expressions of SIRT1, FXR, HO-1, and Nrf2, but decreased NF-κB p65 and TLR4 levels in liver of rats. Taken together, the protective effects of PF on cholestatic liver injury were possibly related to the activation of the SIRT1/FXR and inhibition of NF-κB/NLRP3 inflammasome signaling pathway. These findings might provide a potential protection for 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 Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 504
Author(s):  
Iulia Olimpia Pfingstgraf ◽  
Marian Taulescu ◽  
Raluca Maria Pop ◽  
Remus Orăsan ◽  
Laurian Vlase ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Failure ◽  
Tissue Injury ◽  
Taraxacum Officinale ◽  
Chronic Liver ◽  
Root Extract ◽  
Protective Effects ◽  
Stress Tests ◽  
Chronic Liver Failure

Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.

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