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.

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

scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Simultaneous Inhibition of Three Major Cytokines and Its Therapeutic Effects: A Peptide-Based Novel Therapy against Endotoxemia in Mice

2021 ◽  
Vol 11 (5) ◽  
pp. 436
Author(s):  
Hung-Jen Shih ◽  
Chao-Yuan Chang ◽  
Milton Chiang ◽  
Van Long Le ◽  
Hao-Jen Hsu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Therapeutic Effects ◽  
The Novel ◽  
Tissue Water ◽  
Novel Therapy ◽  
Binding Domains ◽  
Tnf Α ◽  
Simultaneous Inhibition ◽  
Factor Α ◽  
Liver Tissues

Three major cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, mediate endotoxemia-induced liver injury. With the similar structures to the binding domains of the three cytokines to their cognate receptors, the novel peptide KCF18 can simultaneously inhibit TNF-α, IL-1β, and IL-6. We elucidated whether KCF18 can alleviate injury of liver in endotoxemic mice. Adult male mice (BALB/cJ) were intraperitoneally (i.p.) administered lipopolysaccharide (LPS, 15 mg/kg; LPS group) or LPS with KCF18 (LKCF group). Mice in the LKCF group received KCF18 (i.p.) at 2 h (0.6 mg/kg), 4 h (0.3 mg/kg), 6 h (0.3 mg/kg), and 8 h (0.3mg/kg) after LPS administration. Mice were sacrificed after receiving LPS for 24 h. Our results indicated that the binding levels of the three cytokines to their cognate receptors in liver tissues in the LKCF group were significantly lower than those in the LPS group (all p < 0.05). The liver injury level, as measured by performing functional and histological analyses and by determining the tissue water content and vascular permeability (all p < 0.05), was significantly lower in the LKCF group than in the LPS group. Similarly, the levels of inflammation (macrophage activation, cytokine upregulation, and leukocyte infiltration), oxidation, necroptosis, pyroptosis, and apoptosis (all p < 0.05) in liver tissues in the LKCF group were significantly lower than those in the LPS group. In conclusion, the KCF18 peptide–based simultaneous inhibition of TNF-α, IL-1β, and IL-6 can alleviate liver injury in mice with endotoxemia.

scholarly journals Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 139-145
Author(s):  
Jelena Vucic ◽  
Miodrag Vucic ◽  
Tatjana Stankovic ◽  
Hristina Stamenkovic ◽  
Sandra Stankovic ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Late Onset ◽  
Complex Function ◽  
Preterm Neonates ◽  
Control Group ◽  
Premature Neonates ◽  
Early Onset Sepsis ◽  
Ifn Γ ◽  
Venous Plasma

Abstract Not fully maturated immune system in preterm neonates may contribute to the increased susceptibility to infection. The levels of some cytokines can be useful in the prediction and diagnosis of sepsis in premature neonates. In the present study, we evaluated the potential predictive role of IFN-γ and IL-5 in cord and venous blood, together with the determination of C-reactive protein and procalcitonin (PCT) for sepsis development in premature neonates. A total of 80 participants were included. The laboratory results and clinical histories showed that 21 participants had sepsis. Early onset sepsis was detected in 3 patients while late onset sepsis was observed in 18 participants. The venous plasma levels of IFN-γ and PCT was markedly increased in sepsis groups when compared to the participants without sepsis. On the other hand, levels of IL-5 did not significantly change in the evaluated groups of sepsis and in the control group of participants. Simultaneously, plasma venous levels were not altered in any of the evaluated groups. Obtained findings suggest that venous plasma levels of IFN-γ, rather than levels of IFN-γ in cord blood plasma, and PCT may have predictive potential for sepsis development in preterm neonates. Further studies are necessary to get more comprehension of the complex function of cytokines for sepsis development in preterm neonates.

Effect of Curculigo orchioides on Reflux Esophagitis by Suppressing Proinflammatory Cytokines

2012 ◽  
Vol 40 (06) ◽  
pp. 1241-1255 ◽  
Author(s):  
Sae-Kang Ku ◽  
Jae-Soo Kim ◽  
Young-Bae Seo ◽  
Yong-Ung Kim ◽  
Seung-Lark Hwang ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Group Treatment ◽  
Control Group ◽  
Esophageal Mucosa ◽  
Dependent Manner ◽  
Protective Effects ◽  
Model Group ◽  
Curculigo Orchioides ◽  
Intact Group ◽  
Tnf Α

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

scholarly journals Dynamic Changes in MMP1 and TIMP1 in the Antifibrotic Process of Dahuang Zhechong Pill in Rats with Liver Fibrosis

2019 ◽  
Vol 17 (1) ◽  
pp. 346-356
Author(s):  
Jiayu Lin ◽  
Chaowen Deng ◽  
Yanzhong Peng ◽  
Jie Zheng ◽  
Liya Wei ◽  
...  
Keyword(s):  
Treatment Group ◽  
Liver Fibrosis ◽  
Differentially Expressed ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Dynamic Changes ◽  
Matrix Metalloproteinase 1 ◽  
Liver Tissues

AbstractOn the basis of carbon tetrachloride (CCl4)induced liver fibrosis in rats, this study aims to investigate the dynamic changes in matrix metalloproteinase 1 (MMP1) and the tissue inhibitor of metalloproteinase 1 (TIMP1) in the antifibrotic process of Dahuang Zhechong Pill (DHZCP). A total of 50 male Sprague Dawley rats, aged 8 weeks, were randomly divided into 3 groups: the control group, the model group (the group treated with CCl4), and the treatment group (the group treated with CCl4 and DHZCP). Rats were sacrificed at Weeks 4 and 8. Liver tissues were separated for RNA sequencing and bioinformatics analysis. Real-time PCR, Western blot analysis, and histological staining were conducted to confirm the gene expression and pathological change in liver tissues. Compared with control group, rats in model group showed poor mental state and slow weight gain. The liver tissues of the rats in the model group exhibited a damaged hepatic lobule structure, fibrous connective tissue hyperplasia, and inflammatory cell infiltration among the hyperplastic tissues. DHZCP could significantly improve the appearance of rats and alleviate CCl4-induced fibrosis. Compared to model group, 798 differentially expressed mRNAs were found in the treatment group, of which 120 were up-regulated and 678 were down-regulated. Differentially expressed mRNAs between the CCl4-induced group and the DHZCP-treated group were mainly focused on the following KEGG pathways: focal adhesion, phagosome, tight junction, and ECM–receptor interactions. Relative to those in the control group, MMP1 was downregulated, whereas, TIMP1 and Col1A1 were upregulated in the CCl4-induced group at Weeks 4 and 8. DHZCP could reverse MMP1, TIMP1, and Col1A1 expression.DHZCP protects against liver injury and exerts an antifibrotic effect on liver fibrosis induced by CCl4 in rats. Its mechanism may be related to the upregulation of MMP1, downregulation of TIMP1, and promotion of collagen degradation.

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