Pretreatment with dihydroquercetin, a dietary flavonoid, protected against concanavalin A-induced immunological hepatic injury in mice and TNF-α/ActD-induced apoptosis in HepG2 cells

2018 ◽  
Vol 9 (4) ◽  
pp. 2341-2352 ◽  
Author(s):  
Jiajie Chen ◽  
Xu Sun ◽  
Tingting Xia ◽  
Qiqi Mao ◽  
Liang Zhong
Keyword(s):  
Concanavalin A ◽  
Hepg2 Cells ◽  
Hepatic Injury ◽  
Hepatoprotective Effect ◽  
Con A ◽  
Tnf Α ◽  
Dietary Flavonoid ◽  
Induced Apoptosis

We have previously demonstrated the hepatoprotective effect of dihydroquercetin (DHQ) against concanavalin A (Con A)-induced immunological hepatic injury in mice.

Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat

2014 ◽  
Vol 92 (6) ◽  
pp. 490-497 ◽  
Author(s):  
Doaa Ibrahim Mohamed ◽  
Ahmed Abdel salam Mohamed Elmelegy ◽  
Lubna Foaad A. El-Aziz ◽  
Hala Salah Abdel kawy ◽  
Abeer Ahmed AbdEl-Samad ◽  
...  
Keyword(s):  
Body Mass ◽  
Concanavalin A ◽  
Hepatic Injury ◽  
Histopathological Examination ◽  
Smooth Muscle Actin ◽  
Portal Pressure ◽  
Control Group ◽  
Con A ◽  
Alpha Smooth Muscle Actin ◽  
Tnf Α

Tumor necrosis factor alpha (TNF-α) plays an important role in the pathogensis of hepatitis C virus (HCV) infection induced liver injury. This study aimed to evaluate the effects of TNF-α inhibition with pentoxifylline (PTX) on concanavalin A (Con A)-induced hepatic injury in rats. The rats were distributed among 3 groups: (i) control group (1 mL saline·week–1 by intravenous injection (i.v.)); (ii) Con A treatment group (20 mg Con A·(kg body mass)–1·week–1, i.v.), and (iii) rats treated with Con A and with PTX (200 mg PTX·(kg body mass)–1·day–1, per oral) group. Blood samples and livers were collected at the end of weeks 1, 2, 4, and 8 of Con A treatment. Portal pressure (PP) was measured at the end of week 8. The administration of PTX was found to confer significant protection against the injurious effects of Con A on the liver, by reducing serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic TNF-α, and malondialdehyde. Histopathological examination revealed that treatment with PTX significantly suppressed early inflammation, reduced alpha smooth muscle actin, and the apoptosis of hepatocytes induced by Con A. Moreover, PTX significantly (P < 0.05) reduced PP, and quantitative analyses of the area of fibrosis induced by treatment with Con A showed a significant reduction at the end of week 8. We conclude that rats treated with PTX revealed a more or less normal hepatocyte architecture as well as marked improvement in fibrosis and PP.

Hepatoprotective effect of Omega-3 PUFAs against acute paracetamol-induced hepatic injury confirmed by FTIR

2020 ◽  
pp. 096032712095452
Author(s):  
Zeinab A El-Gendy ◽  
Seham A El-Batran ◽  
SAH Youssef ◽  
A Ramadan ◽  
Walid El Hotaby ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Hepatoprotective Effect ◽  
Omega 3 ◽  
Oral Ingestion ◽  
Tnf Α ◽  
Hepatoprotective Agent ◽  
Biochemical Analyses ◽  
Protein Alterations

Acute paracetamol over dose-induced hepatotoxicity is considered an important medical hazard especially among women. Omega-3 long-chain polyunsaturated fatty acids (Omega-3 PUFAs) daily doses are nowadays recommended for their antioxidant and anti-inflammatory potentials. Fourier transform infrared (FTIR) spectroscopy is considered a reliable method in analyzing cellular alterations and is now efficiently used to diagnose several diseases and the efficacy of drugs even in the early stages. The aim of our study was to evaluate the hepatoprotective effect of Omega-3 PUFAs against paracetamol-induced hepatotoxicity in rats confirmed through measuring protein alterations in hepatocytes by FTIR. Rats were pretreated with Omega-3 PUFAs (50 and 100 mg/kg) for 21 days prior to oral ingestion of paracetamol. FTIR results revealed that Omega-3 PUFAs (50 mg/kg) limited the toxic effects of paracetamol by restoring the hepatic amide I to amide II ratio. In addition; biochemical analyses demonstrated that serum ALT, AST, Cholesterol, LDL-cholesterol and Il-6 levels as well as hepatic TNF-α, MDA, NOx levels were decreased. Besides; serum HDL-cholesterol level and hepatic GSH level were increased. Histopathological examinations of hepatic sections validated the hepatoprotective potential. The overall effect of this dose was comparable to those of the usual recommended hepatoprotective supplement; silymarin. In conclusion; it would be recommended to use Omega-3 PUFAs in low doses on daily bases as a hepatoprotective agent.

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.

scholarly journals Extracts from Fermented Black Garlic Exhibit a Hepatoprotective Effect on Acute Hepatic Injury

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1112 ◽  
Author(s):  
Jen-Chieh Tsai ◽  
Yi-An Chen ◽  
Jung-Tsung Wu ◽  
Kuan-Chen Cheng ◽  
Ping-Shan Lai ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Interleukin 1 ◽  
Water Layer ◽  
Hepatoprotective Effect ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Acute Hepatic Injury ◽  
Factor Alpha ◽  
Anti Inflammatory

The mechanism of hepatoprotective compounds is usually related to its antioxidant or anti-inflammatory effects. Black garlic is produced from garlic by heat treatment and its anti-inflammatory activity has been previously reported. Therefore, the aim of this study was to investigate the hepatoprotective effect of five different extracts of black garlic against carbon tetrachloride (CCl4)-induced acute hepatic injury (AHI). In this study, mice in the control, CCl4, silymarin, and black garlic groups were orally administered distilled water, silymarin, and different fraction extracts of black garlic, respectively, after CCl4 was injected intraperitoneally to induce AHI. The results revealed that the n-butanol layer extract (BA) and water layer extract (WS) demonstrated a hepatoprotective effect by reducing the levels of alanine aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA). Furthermore, the BA and WS fractions of black garlic extract increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), tumor necrosis factor alpha (TNF-α), and the interleukin-1 (IL-1β) level in liver. It was concluded that black garlic exhibited significant protective effects on CCl4-induced acute hepatic injury.

TNFR1/TNF-α and mitochondria interrelated signaling pathway mediates quinocetone-induced apoptosis in HepG2 cells

2013 ◽  
Vol 62 ◽  
pp. 825-838 ◽  
Author(s):  
Chaoming Zhang ◽  
Congcong Wang ◽  
Shusheng Tang ◽  
Yu Sun ◽  
Dongxu Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Tnf Α ◽  
Induced Apoptosis

scholarly journals 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Tingmei Ye ◽  
Xueting Cai ◽  
Jie Yang ◽  
Wuguang Lu ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Human Tumor ◽  
Tumor Burden ◽  
Tumor Xenograft ◽  
Apoptotic Protein ◽  
Dietary Flavonoid ◽  
Induced Apoptosis

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burdenin vivoin a HepG2 tumor xenograft model. Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2. These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy.

scholarly journals Protective Effect of Eugenol against Acetaminophen-Induced Hepatotoxicity in Human Hepatocellular Carcinoma Cells via Antioxidant, Anti-Inflammatory, and Anti-Necrotic Potency

2021 ◽  
Vol 9 (A) ◽  
Author(s):  
Florenly Florenly ◽  
Liena Sugianto ◽  
I Nyoman Ehrich Lister ◽  
Ermi Girsang ◽  
Chrismis Novalinda Ginting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepg2 Cells ◽  
Hepatoprotective Effect ◽  
Protective Effects ◽  
Cyp 2E1 ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Apoptotic Activity ◽  
Factor Α

BACKGROUND: Overdoses acetaminophen (APAP) could cause acute liver failure, even though it used is for analgesics. APAP could cause hepatotoxicity due to multiple mediators of inflammation and oxidative stress. Eugenol has been reported to have anti-inflammatory and antioxidant activity but its hepatoprotective effect has not been widely reported. AIM: The purpose of this research is to know if eugenol could protect HepG2 cells from APAP. METHODS: HepG2 that induced by APAP as hepatotoxicity cells model was treated by using eugenol at 6.25 and 25 μg/mL. The protective effects of eugenol toward hepatotoxicity were evaluated by determine tumor necrosis factor-α (TNF-α) concentration, apoptotic activity, reactive oxygen species (ROS) level, also cytochrome (CYP)2E1 and GPX gene expression. RESULTS: Eugenol at 6.25 and 25 μg/mL concentration can reduce TNF-α concentration, the apoptotic, necrotic, dead cells, and ROS level. Besides it can increase the gene expression (GPX and CYP2E1). The best hepatoprotective effect was found when using the eugenol at 25 μg/mL. CONCLUSION: Therefore, eugenol can be used to protect HepG2 cells against APAP.

Concanavalin A-induced Aggregation of Human Blood Platelets

1975 ◽  
Vol 33 (02) ◽  
pp. 354-360 ◽  
Author(s):  
Heinrich Patscheke ◽  
Reinhard Brossmer
Keyword(s):  
Concanavalin A ◽  
Binding Capacity ◽  
Specific Binding ◽  
Blood Platelets ◽  
Residual Effect ◽  
Independent Effect ◽  
Con A ◽  
Experimental Conditions ◽  
Main Effect ◽  
Induced Aggregation

SummaryConcanavalin A (CON A) causes platelets to aggregate. A Ca++-independent effect of CON A could be separated from a main effect which depends on Ca++. The main effect probably is a consequence of the CON A-induced platelet release reaction and therefore is platelet-specific. The weak residual effect observed in the presence of Na2EDTA may be due to a similar mechanism as has been demonstrated for CON A-induced aggregations of several other normal and malignant transformed animal cells.Na2EDTA did not inhibit the carbohydrate-specific binding capacity of CON A. Therefore, Na2EDTA appears not to demineralize the CON A molecules under these experimental conditions.α-methyl-D-glucoside inhibits the Ca++-independent as well as the Ca++-dependent effect of CON A.Pretreatment by neuraminidase stimulated the platelet aggregation induced by CON A. It is possible that removal of terminal sialic acid residues makes additional receptors accessible for the binding of CON A.

Induction of Apoptosis by Nano‐Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Thoria Diab ◽  
Tarek M. Mohamed ◽  
Alaa Hamed ◽  
Mohamed Gaber
Keyword(s):  
Cell Cycle ◽  
Metal Complexes ◽  
Hepg2 Cells ◽  
Therapeutic Potential ◽  
Free Ligand ◽  
Organometallic Complexes ◽  
Phase Cell ◽  
Sod Activity ◽  
Induced Apoptosis

Background: Chemotherapy is currently the most utilized treatment for cancer. Therapeutic potential of metal complexes in cancer therapy has attracted a lot of interest. The mechanisms of action of most organometallic complexes are poorly understood. Objective: This study was designed to explore the mechanisms governing the anti-proliferative effect of the free ligand N1,N6‐bis((2‐hydroxynaphthalin‐1‐yl)methinyl)) adipohydrazone (H2L) and its complexes of Mn(II), Co(II), Ni(II) and Cu(II). Methods: Cells were exposed to H2L or its metal complexes where cell viability determined by MTT assay. Cell cycle was analysed by flow cytometry. In addition, qRT-PCR was used to monitor the expression of Bax and Bcl-2. Moreover, molecular docking was carried out to find the potentiality of Cu(II) complex as an inhibitor of Adenosine Deaminase (ADA). ADA, Superoxide Dismutase (SOD) and reduced Glutathione (GSH) levels were measured in the most affected cancer cell line. Results: The obtained results demonstrated that H2L and its Cu(II) complex exhibited a strong cytotoxic activity compared to other complexes against HepG2 cells (IC50 = 4.14±0.036μM/ml and 3.2±0.02μM/ml), respectively. Both H2L and its Cu(II) complex induced G2/M phase cell cycle arrest in HepG2 cells. Additionally, they induced apoptosis in HepG2 cells via upregulation of Bax and downregulation of Bcl-2. Interestingly, the activity of ADA was decreased by 2.8 fold in HepG2 cells treated with Cu(II) complex compared to untreated cells. An increase of SOD activity and GSH level in HepG2 cells compared to control was observed. Conclusion: The results concluded that Cu(II) complex of H2L induced apoptosis in HepG2 cells. Further studies are needed to confirm its anti-cancer effect in vivo.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

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