The Protective Effect of Aesculus hippocastanum (Venoplant®) Against Concanavalin A-Induced Liver Injury

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 196-206 ◽  
Author(s):  
Shujin Wu ◽  
Rina Sa ◽  
Zhirong Gu ◽  
Pei Zhao ◽  
Jing Yu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cytochrome C ◽  
Concanavalin A ◽  
Cell Apoptosis ◽  
Liver Tissue ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Aesculus Hippocastanum ◽  
Tnf Α ◽  
Ifn Γ

Aim: The present study was performed to investigate the effect of Aesculus hippocastanum (AH; Venoplant®) on concanavalin A (ConA)-induced acute liver injury and explore the mechanism in mice. Methods: ConA (20 mg/kg) was administered via tail vein injection to induce hepatic damage. The groups of AH (Venoplant®) were given at 65.8, 131.6, and 263.2 mg/kg by oral gavages for 20 days. The serum levels of aspartate transaminase (AST), alanine aminotransferase (ALT), total protein (TP), and albumin (Alb) were determined by automatic biochemical analyzer, and the Alb/globulin (A/G) ratio was calculated. Tumor necrosis factor-α (TNF-α) and IFN-γ levels were assayed by enzyme-linked immunosorbent assay. The liver tissue was attained by hematoxylin and eosin, and the histopathological changes were calculated. The cell apoptosis was assayed by terminal dUTP nick-end labeling. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) content of liver tissue were assayed by related kits. The activity of caspase-3 was detected by spectrophotometry. The expressions of cytochrome c, Bax, Bcl-2, c-Jun N-terminal kinase (JNK), and p-JNK were detected by western blot. Results: The results showed that the levels of ALT, AST, IFN-γ, and TNF-α in AH (Venoplant®) groups were significantly lower than those in ConA-injured group, while the levels of TP, Alb, and A/G were significantly higher. The SOD and GSH levels were significantly increased, and the MDA level was decreased; liver histopathology was changed consistently with the serological indicators, AH (Venoplant®) treatment significantly reduced the pathological damage and cell apoptosis; while in AH (Venoplant®) group, the expressions of cytochrome c, caspase-3, Bax/Bcl-2 ratio, and p-JNK were significantly decreased. Conclusion: AH (Venoplant®) could significantly protect the ConA-induced acute liver injury in mice via inhibition of reactive oxygen species and JNK pathway.

scholarly journals SHED ameliorated concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis

2020 ◽  
Author(s):  
Yikun Zhou ◽  
Ruili Yang ◽  
Lingsu Zhu ◽  
Huaming Huang ◽  
Shengjie Cui ◽  
...  
Keyword(s):  
Liver Injury ◽  
Autoimmune Hepatitis ◽  
Concanavalin A ◽  
Acute Liver Injury ◽  
Deciduous Teeth ◽  
Protective Effects ◽  
Hepatocyte Apoptosis ◽  
Con A ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background：Autoimmune hepatitis (AIH) is serious autoimmune liver diseases that threaten people’s health worldwide, emphasizing the need to identify novel treatment. Stem cells from human exfoliated deciduous teeth (SHED), which is easy to obtain and non-invasive, showed pronounced proliferation and immunomodulation capacity. This study aims to investigate the effect of SHED on ConA-induced AIH and the potential underlying mechanisms.Methods: We used a concanavalin A (ConA) induced acute hepatitis mouse model and in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis and the underlying mechanisms.Results: SHED infusion could prevent aberrant histopathological architecture of liver with infiltration of abundant of CD3+, CD4+, TNF-α+ and IFN-γ+ inflammatory cells induced by ConA. The expression of ALT and AST which indicated the liver function significantly elevated in hepatitis mice. While SHED infusion could block the elevation of ALT and AST induced by ConA. Mechanistically, Con-A upregulated TNF-α and IFN-γ expression activated NF-κB pathways to induced hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from Con-A-induced apoptosis. Conclusions: These results demonstrated that SHED alleviated ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the NF-κB pathways. Our findings could provide a potential prevention and therapeutic strategy for hepatitis and acute hepatic injury.

IL-6, IFN-γ and TNF-α production by liver-associated T cells and acute liver injury in rats administered concanavalin A

1998 ◽  
Vol 76 (6) ◽  
pp. 542-549 ◽  
Author(s):  
Qi Cao ◽  
Robert Batey ◽  
Gerald Pang ◽  
Adrian Russell ◽  
Robert Clancy
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Concanavalin A ◽  
Acute Liver Injury ◽  
Tnf Α ◽  
Ifn Γ

Protective effect of Trillium tschonoskii saponin on CCl4-induced acute liver injury of rats through apoptosis inhibition

2016 ◽  
Vol 94 (12) ◽  
pp. 1291-1297 ◽  
Author(s):  
Hao Wu ◽  
Yong Qiu ◽  
Ziyang Shu ◽  
Xu Zhang ◽  
Renpeng Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Protective Role ◽  
High Dose ◽  
Dependent Manner ◽  
Hepatocyte Apoptosis ◽  
Liver Index ◽  
Tnf Α ◽  
Trillium Tschonoskii

To explore hepatoprotective role and underlying mechanisms of Trillium tschonoskii Maxim (TTM), 36 rats were randomly divided into control, CCl4-induced liver injury model, and biphenyl dimethyl dicarboxylate (DDB) and low-, moderate-, and high-dose TTM treatment groups. After CCl4-induced model establishment, the rats from DDB and TTM groups were administrated with DDB at 0.2 g/kg per day and TTM at 0.1, 0.5, and 1.0 g/kg per day, while the rats from control and model groups were administrated with saline. After 5 days of treatments, all rats were sacrificed for determining serum ALT and AST levels and liver index, examining histopathological changes in liver through HE and TUNEL staining, and evaluating TNF-α and IL-6 mRNA expression by real-time PCR, and caspase-3, Bcl-2, and Bax expression by Western blot. Results indicated that CCl4 could induce acute liver injury and abnormal liver function in rats with obvious hepatomegaly, increased liver index, high ALT and AST levels, up-regulated TNF-α and IL-6, and overexpressed Bax and caspase-3. However, DDB and TTM could execute protective role in CCl4-induced liver injury in rats through reducing ALT and AST levels, rescuing hepatomegaly, down-regulating inflammatory factors and inhibiting hepatocyte apoptosis in a dose-dependent manner. Therefore, TTM has obvious protective role in CCl4-induced liver injury of rats through inhibiting hepatocyte apoptosis.

Short-form Ron receptor is required for normal IFN-γ production in concanavalin A-induced acute liver injury

2007 ◽  
Vol 292 (1) ◽  
pp. G253-G261 ◽  
Author(s):  
Cynthia C. Wetzel ◽  
Mike A. Leonis ◽  
Arlene Dent ◽  
Meredith A. Olson ◽  
Angela M. Longmeier ◽  
...  
Keyword(s):  
Liver Injury ◽  
Concanavalin A ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Ex Vivo ◽  
Short Form ◽  
Cell Receptor ◽  
Ron Receptor ◽  
Ifn Γ

Abrogation of Ron receptor tyrosine kinase function results in defects in macrophage activation and dysregulated acute inflammatory responses in vivo. Several naturally occurring constitutively active alternative forms of Ron have been identified, including from primary human tumors and tumor cell lines. One of these alternative forms, short-form (SF) Ron, is generated from an alternative start site in intron 10 of the Ron gene that eliminates most of the extracellular portion of the receptor and is overexpressed in several human cancers. To test the physiological significance of SF-Ron in vivo, mice were generated that solely express the full-length form of Ron (FL-Ron). Our results show that elimination of the capacity to express SF-Ron in vivo leads to augmented production of IFN-γ from splenocytes following stimulation ex vivo with either concanavalin A or anti-CD3/T cell receptor monoclonal antibody. Moreover, in a concanavalin A-induced murine model of acute liver injury, FL-Ron mice have increased production of serum INF-γ and serum alanine aminotransferase levels and worsened liver histology and overall survival compared with wild-type control mice. Taken together, these results suggest for the first time that SF-Ron impacts the progression of inflammatory immune responses in vivo and further support a role for the Ron receptor and its various forms in liver pathophysiology.

scholarly journals The molecular mechanism of acute liver injury and inflammatory response induced by Concanavalin A

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Xiaoxiao Liu ◽  
Ting Yu ◽  
Yuzhu Hu ◽  
Longzhen Zhang ◽  
Junnian Zheng ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Injury ◽  
Concanavalin A ◽  
Acute Liver Injury ◽  
Mapk Pathway ◽  
Underlying Mechanism ◽  
Kinase Domain ◽  
Mitogen Activated Protein Kinase ◽  
Tnf Α ◽  
Hepatocyte Death

AbstractAcute liver injury is a common but urgent clinical condition, and its underlying mechanism remains to be further elucidated. Concanavalin A (ConA)-induced liver injury was investigated in the study. Different from the caspase-dependent cell apoptosis in lipopolysaccharide/D-aminogalactose (LPS/D-GalN) induced liver injury, ConA-induced hepatocyte death was independent on caspase. Increased hepatocytic expressions of mixed lineage kinase domain like (MLKL) and receptor-interacting protein kinase 1 (RIPK1), and higher serum concentration of tumor necrosis factor-α (TNF-α) were noticed in mice with ConA-induced liver injury. Inhibition of RIPK1 protein or deletion of MLKL gene could significantly attenuate the acute liver injury and improve mice survival. Besides, the ConA treatment induced severe hepatic inflammation in wide type (WT) mice in comparison with Mlkl−/− mice, suggesting the RIPK1-MLKL-mediated hepatocellular necroptosis might participate in the process of liver injury. Moreover, mitochondrial damage associated molecular patterns (DAMPs) were subsequently released after the hepatocyte death, and further activated the p38 mitogen-activated protein kinase (MAPK) pathway, which could be reduced by deletion or inhibition of Toll-like receptor 9 (TLR9). Taken together, our research revealed that ConA-induced acute liver injury was closely related to TNF-α-mediated cell necroptosis, and inhibiting RIPK1 or deleting MLKL gene could alleviate liver injury in mice. The mitochondrial DNA released by dead hepatocytes further activated neutrophils through TLR9, thus resulting in the exacerbation of liver injury.

scholarly journals Hepatoprotective Effects of Lactobacillus on Carbon Tetrachloride-Induced Acute Liver Injury in Mice

2018 ◽  
Vol 19 (8) ◽  
pp. 2212 ◽  
Author(s):  
Xiaoyong Chen ◽  
Jing Zhang ◽  
Ruokun Yi ◽  
Jianfei Mu ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Lactobacillus Plantarum ◽  
Protein Level ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Lactobacillus Fermentum ◽  
Expression Levels ◽  
Tnf Α

The aim of this study was to investigate and compare the effects of heat-killed and live Lactobacillus on carbon tetrachloride (CCl4)-induced acute liver injury mice. The indexes evaluated included liver pathological changes, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the serum, related gene expression (IL-1β, TNF-α, Bcl-2, and Bax), and related proteins levels (Bax, Bcl-2, Caspase 3, and NF-κB p65). Compared with the model group, the results indicated that the levels of ALT, AST, and MDA in the serum, the expression levels of IL-1β, TNF-α, and Bax, and the protein levels of Bax, Caspase 3, and NF-κB p65 significantly decreased, and the pathologic damage degree all significantly reduced after live Lactobacillus fermentum (L-LF) and live Lactobacillus plantarum (L-LP) treatment. Additionally, the levels of SOD and GSH in the serum, the gene expression of Bcl-2, and the protein level of Bcl-2 significantly increased after L-LF and L-LP treatment. Although HK-LF and HK-LP could also have obvious regulating effects on some of the evaluated indexes (ALT, AST, the expression levels of TNF-α and Bax, and the protein level of Bcl-2) and play an important role in weakening liver damage, the regulating effects of L-LF or L-LP on these indexes were all better compared with the corresponding heat-killed Lactobacillus fermentum (HK-LF) and heat-killed Lactobacillus plantarum (HK-LP). Therefore, these results suggested that LF and LP have an important role in liver disease.

scholarly journals Magnesium isoglycyrrhizinate protects against concanavalin A-induced immunological liver injury in a mouse model

2019 ◽  
Vol 27 (3) ◽  
pp. 281-290
Author(s):  
Zhengyan Jiang ◽  
Liang Zheng
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Concanavalin A ◽  
Plasma Levels ◽  
Control Group ◽  
Model Group ◽  
Tnf Α ◽  
Ifn Γ ◽  
Magnesium Isoglycyrrhizinate ◽  
Liver Tissues

Abstract Background: To evaluate the protective effects of magnesium isoglycyrrhizinate on a mouse model of concanavalin A (ConA)-induced immunological liver injury. Materials and Methods: Forty-eight mice were randomly divided into a normal control group, a model group, three dose groups of magnesium isoglycyrrhizinate (12.5, 25, 50 mg/kg) and a dexamethasone group (2.5 mg/kg). Magnesium isoglycyrrhizinate was intraperitoneally injected for 5 consecutive days, and the model of immunological liver injury was established on the fifth day after caudal vein injection of ConA (20 mg/kg). Blood was collected to detect the activities of alanine transaminase (ALT) and aspartate transaminase (AST) as well as the levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The levels of neopterin (NP) and malondialdehyde (MDA) and the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in liver tissues were measured, and histopathological changes were observed. Results: The serum levels of ALT and AST in the model group increased. Hepatic lobules had necrotic foci and inflammatory cell infiltration. The plasma levels of TNF-α and IFN-γ increased. In liver tissues, the levels of NP, MDA and MPO rose, but that of SOD decreased. Magnesium isoglycyrrhizinate significantly attenuated the activities of ALT and AST (P<0.05). Histopathological staining showed that inflammation of the liver was relieved significantly. Magnesium isoglycyrrhizinate also decreased the levels of NP, MDA and MPO in liver tissues (P<0.05), raised that of SOD and reduced the plasma levels of TNF-α and IFN-γ (P<0.05). Conclusion: Magnesium isoglycyrrhizinate protected against ConA-induced immunological liver injury in mice, probably through immune regulation and antioxidation.

scholarly journals The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Su-Zhi Xie ◽  
Xiang-Yang Zhai ◽  
Sheng-Yan Xi ◽  
Ying-Kun Qiu ◽  
Yu-Mei Zhang ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Protein Expression ◽  
Liver Tissue ◽  
Intraperitoneal Injection ◽  
Acute Liver Injury ◽  
Peanut Oil ◽  
Protective Effects ◽  
Liver Index ◽  
Tnf Α

Background:Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI).Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms.Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined.Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI.Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

scholarly journals Protective effect of Toxocara vitulorum extract against alpha-naphthylisothiocyanate-induced cholangitis in rat

2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Abeer Mahmoud Badr ◽  
Mohamed Farid ◽  
Ahmed Abdel Aziz Biomy ◽  
Ayman Saber Mohamed ◽  
Noha Ahmed Mahana ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Wistar Rat ◽  
Liver Function Tests ◽  
T Helper ◽  
Standard Drug ◽  
Toxocara Vitulorum ◽  
Stress Markers ◽  
Tnf Α ◽  
Ifn Γ ◽  
Antioxidant Markers

Abstract Background Cholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. The present study aims to evaluate the protective impact of an ascarid nematode Toxocara vitulorum extract (TvE) against alpha-naphthylisothiocyanate (ANIT)-induced cholangitis male wistar rat model compared to ursodeoxycholic acid (UDCA) as a standard drug. Results Pretreatment with TvE and/or UDCA induced a marked reduction in the levels of liver function tests and malondialdehyde, while antioxidant markers were increased compared to cholestatic rats. Pretreatment with either TvE or combination before cholangitis induction attenuated the predominant Th1-related cytokines (IFN-γ and TNF-α) to Th2 (IL-13 and IL-10). TvE administration promoted higher expression levels of Bcl-2 protein and lower levels of caspase-3 compared to cholestatic rats. Conclusions Treatment with TvE has improved the liver functions and elevated the levels of oxidative stress markers. The upregulation of Th2-related cytokines and suppression of apoptosis through caspase-3 might be considered as a potential mechanism of TvE. Thereby, this natural extract revealed an opportunity for use in treatment of cholangitis disease.

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