The effects of TNF-α inhibitors on carbon tetrachloride-induced nephrotoxicity

Background: Over the years, Alisma Shugan Decoction (ASD), because of its potent anti-inflammation activity, has been used in traditional Chinese medicine (TCM) for treatment of many inflammation-associated disorders including those of the heart, blood vessel and brain. Methods: Herein, we examined the probable therapeutic effect of ASD in carbon tetrachloride (CCI4)-induced liver injury and fibrosis mice models. Results: Our results demonstrate that ASD dose-dependently reduced the fibrosis-related increased collagen deposition secondary to liver tissue exposure to CCI4. Data from our biochemical analyses showed significantly less liver damage biomarkers including ALT, AST and hydroxyproline in the ASD-treated samples, suggesting hepato-protective effect of ASD. Furthermore, we demonstrated that treatment with ASD significantly reversed CCI4-induced elevation of TNF-α, IL-6, IL-1β and MCP-1. Comparative immunohistochemical staining of liver samples revealed that ASD dose-dependently downregulated the expression of pro-apoptotic, Bax while upregulating anti-apoptotic Bcl2 protein. Interestingly, NF-κB signaling, a principal regulator of inflammation was markedly suppressed by ASD treatment. In addition, treatment with ASD deregulated stress signaling pathways by suppressing the expression of markers of unfolded protein response, such as ATF6, IRE and GRP78. Conclusion: In conclusion, the present study provides preclinical evidence for the use of ASD as an efficacious therapeutic option in cases of chemical-induced liver damage and/or fibrosis. Further large-cohort validation of these findings is warranted.

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Preventive Effect of Blueberry Extract on Liver Injury Induced by Carbon Tetrachloride in Mice

Foods ◽

10.3390/foods8020048 ◽

2019 ◽

Vol 8 (2) ◽

pp. 48 ◽

Cited By ~ 10

Author(s):

Bihui Liu ◽

Yuan Fang ◽

Ruokun Yi ◽

Xin Zhao

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Messenger Rna ◽

Tbars Level ◽

Preventive Effect ◽

Polyphenol Content ◽

Sod Activity ◽

Standard Drug ◽

Tnf Α ◽

Ifn Γ

The blueberry is a common fruit that is rich in nutritional value and polyphenol substances. In this study, the blueberry polyphenol content in extract was analysed by spectrophotometry. The results showed that the blueberry polyphenol content in the extract reached 52.7%. A mouse model of liver injury induced by carbon tetrachloride (CCl4) was established to study the preventive effect of blueberry extract (BE) on liver injury in mice and the experimental animals were examined using biochemical and molecular biological methods. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are important clinical liver function indicators; the changes of triglyceride (TG) and total cholesterol (TC) are observed after liver injury; interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) are important inflammatory indexes; superoxide dismutase (SOD) activity and thiobarbituric acid reactive substances (TBARS) are important changes of oxidative stress indexes. The in vivo animal experiment results showed that BE decreased the liver index of mice with liver injury, BE could reduce the AST, ALT, TG and TC levels and also could reduce the serum cytokine IL-6, TNF-α and IFN-γ levels in mice with liver injury. Moreover, BE increased the SOD activity and decreased the TBARS level in the gastric tissues of mice with liver injury. After treatment with the highest concentration of BP in liver injury mice, these levels returned close to those obtained after treatment with the standard drug of silymarin. Detection of messenger RNA (mRNA) in liver tissue showed that BE upregulated the Cu/Zn-SOD, Mn-SOD and chloramphenicol acetyltransferase (CAT) expression levels and downregulated cyclooxygenase (COX)-2 expression. The effect of BE on mice with liver injury was positively correlated with the BE concentration and was similar to that of silymarin, which is a drug for liver injury, suggesting that BE had a good preventive effect on liver injury. Thus, BE rich in polyphenols is a bioactive substance with value for development and utilization.

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EGR-1 mediated TNF α production is associated with hepatoprotection after acute carbon tetrachloride exposure in mice

Cytokine ◽

10.1016/j.cyto.2009.07.504 ◽

2009 ◽

Vol 48 (1-2) ◽

pp. 119

Author(s):

Michele T. Pritchard ◽

Jessica I. Cohen ◽

Sanjoy Roychowdhury ◽

Laura E. Nagy

Keyword(s):

Carbon Tetrachloride ◽

Tnf Α

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The protective effect of chrysin against carbon tetrachloride-induced kidney and liver tissue damage in rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000653 ◽

2020 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Burcu Gul Baykalir ◽

Aslihan Sur Arslan ◽

Seda Iflazoglu Mutlu ◽

Tuba Parlak Ak ◽

Ismail Seven ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Group Treatment ◽

Histopathological Examination ◽

Kidney Tissue ◽

Control Group ◽

Protective Effects ◽

Sod Activity ◽

Tnf Α ◽

Liver And Kidney ◽

Factor Α

Abstract: The aim of this study was to investigate the possible protective effects of chrysin on oxidative status and histological alterations against carbon tetrachloride (CCl4)-induced liver and kidney tissue in rats. The animals were randomly divided into four groups; the control, chrysin (100 mg/kg), CCl4 (0.5 ml/kg) and chrysin + CCl4 groups. Liver and kidney injuries were assessed by biochemical and histopathological examinations. The levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity were measured in tissues. Serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels were also measured in blood samples. MDA, serum TNF-α, AST, ALT, urea, and creatinine levels (p < 0.05) were significantly higher, and SOD activity and GSH level were significantly (p < 0.05) lower in the CCl4 group than in the control group. Treatment with chrysin in the chrysin + CCl4 group decreased MDA, AST, ALT, creatinine, and TNF-α levels (p < 0.05), and increased SOD activity, GSH levels (p < 0.05), and serum TNF-α levels (p < 0.05). In addition, body weight change (BWC) (p < 0.05) and feed intake (FI) were significantly lower (p < 0.001) in the CCl4 group than in the control group. Moreover, treatment with chrysin increased BWC and FI in the chrysin + CCl4 group compared with that in the CCl4 group. These findings also confirmed by histopathological examination. The chrysin treatment ameliorated the CCl4-induced biochemical and pathological alterations. These results demonstrated that chrysin provided amelioration on the rat liver and kidney tissues CCl4-induced injury by increasing the antioxidant activity.

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Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats

Drug Research ◽

10.1055/a-1589-5395 ◽

2021 ◽

Author(s):

Ahmad Reza Dehpour ◽

Hasan Yousefi-Manesh ◽

Mohammad Sheibani ◽

Mohammad Amin Sadeghi ◽

Sara Hemmati ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Histopathological Examination ◽

Serum Levels ◽

Control Group ◽

Adult Rats ◽

Toxic Agents ◽

Tnf Α ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Pre Treatment

AbstractThe liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1β and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.

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Therapeutic Effect of Biejiaxiaozheng Pills on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through the NF-κB/Nrf2 Pathway

Gastroenterology Research and Practice ◽

10.1155/2021/3954244 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Weibin Wu ◽

Liqiang Li ◽

Jian Yang ◽

Pinyu Li ◽

Yuying Hu ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Function ◽

Hepatic Fibrosis ◽

Inflammatory Cytokine ◽

Nrf2 Pathway ◽

Tnf Α ◽

Cytokine Levels ◽

Commercial Kits ◽

Plasma Antioxidant ◽

Masson Staining

Aims. To explore the effects of Biejiaxiaozheng pills on carbon tetrachloride-induced hepatic fibrosis in rats through the NF-κB/Nrf2 pathway and to explore the possible antifibrotic mechanisms of the drug. Material and Method. A rat model of hepatic fibrosis was established via CCl4 induction. Liver function and antioxidant indices were detected using commercial kits. Hematoxylin-eosin and Masson staining were used to detect pathological changes in hepatic tissues. ELISA was used to measure plasma TNF-α, IL-β, and IL-6 levels. RT-PCR was used to measure changes in TNF-α, IL-β, and IL-6 levels in hepatic tissues. Changes in p65, P-p65, Nrf2, and HO-1 protein expression were detected using western blotting. Results. In rats with hepatic fibrosis, Biejiaxiaozheng pills effectively improved liver function, alleviated fibrosis in hepatic tissues, and significantly reduced collagen accumulation. The pills significantly downregulated inflammatory cytokine expression in hepatic tissues by suppressing p65 phosphorylation and reduced plasma inflammatory cytokine levels to some extent. The pills upregulated Nrf2 and HO-1 expression in hepatic tissues, enhanced antioxidant potential, and upregulated plasma antioxidant levels. Conclusion. Biejiaxiaozheng pills improved hepatic fibrosis symptoms and lesions in rats, likely by inhibiting the NF-κB pathway and promoting the Nrf2 pathway.

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Antisense Tissue Factor Oligodeoxynucleotides Protected Diethyl Nitrosamine/Carbon Tetrachloride-Induced Liver Fibrosis Through Toll Like Receptor4-Tissue Factor-Protease Activated Receptor1 Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.676608 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maha M. Shouman ◽

Rania M. Abdelsalam ◽

Mahmoud M. Tawfick ◽

Sanaa A. Kenawy ◽

Mona M. El-Naa

Keyword(s):

Gene Expression ◽

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Tissue Factor ◽

Transforming Growth Factor ◽

Liver Enzymes ◽

Smooth Muscle Actin ◽

Coagulation Factor ◽

Enzymes Activities ◽

Tnf Α

Tissue factor (TF) is a blood coagulation factor that has several roles in many non-coagulant pathways involved in different pathological conditions such as angiogenesis, inflammation and fibrogenesis. Coagulation and inflammation are crosslinked with liver fibrosis where protease-activated receptor1 (PAR1) and toll-like receptor4 (TLR4) play a key role. Antisense oligodeoxynucleotides are strong modulators of gene expression. In the present study, antisense TF oligodeoxynucleotides (TFAS) was evaluated in treating liver fibrosis via suppression of TF gene expression. Liver fibrosis was induced in rats by a single administration of N-diethyl nitrosamine (DEN, 200 mg/kg; i. p.) followed by carbon tetrachloride (CCl4, 3 ml/kg; s. c.) once weekly for 6 weeks. Following fibrosis induction, liver TF expression was significantly upregulated along with liver enzymes activities and liver histopathological deterioration. Alpha smooth muscle actin (α-SMA) and transforming growth factor-1beta (TGF-1β) expression, tumor necrosis factor-alpha (TNF-α) and hydroxyproline content and collagen deposition were significantly elevated in the liver. Blocking of TF expression by TFAS injection (2.8 mg/kg; s. c.) once weekly for 6 weeks significantly restored liver enzymes activities and improved histopathological features along with decreasing the elevated α-SMA, TGF-1β, TNF-α, hydroxyproline and collagen. Moreover, TFAS decreased the expression of both PAR1 and TLR4 that were induced by liver fibrosis. In conclusion, we reported that blockage of TF expression by TFAS improved inflammatory and fibrotic changes associated with CCl4+DEN intoxication. In addition, we explored the potential crosslink between the TF, PAR1 and TLR4 in liver fibrogenesis. These findings offer a platform on which recovery from liver fibrosis could be mediated through targeting TF expression.

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

International Journal of Molecular Sciences ◽

10.3390/ijms19082212 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2212 ◽

Cited By ~ 22

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.

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AMELIORATIVE EFFECT OF HESPERIDIN ON CARBON TETRACHLORIDE INDUCED LIVER FIBROSIS IN RATS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i7.17611 ◽

2017 ◽

Vol 9 (7) ◽

pp. 45 ◽

Cited By ~ 2

Author(s):

Asmaa Ramadan Abdel-sttar ◽

Marwa Mahmoud Khalaf ◽

Amira M. Aboyoussef ◽

Ali Ahmed Abosaif

Keyword(s):

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Liver Function ◽

Lipid Profile ◽

Transforming Growth Factor ◽

Density Lipoprotein ◽

Liver Weight ◽

Transforming Growth Factor Β1 ◽

Control Group ◽

Tnf Α

Objective: Exposure to carbon tetrachloride leads to serious liver injury and fibrosis. This study was aimed to evaluate the hepatoprotective effects of hesperidin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats compared with the reference drug silymarin. Methods: Wistar albino rats were divided into five groups, each of eight rats. Animals were allocated into a control group, corn oil group and fibrosis control group. The remaining two groups received in addition to CCl4, silymarin (100 mg/kg/d) as a reference treatment and hesperidin (200 mg/kg/d). At the end of experimental period, the biomarkers of specific fibrosis [hepatic transforming growth factor β1 (TGF-β1) and hydroxyproline (HYP)], liver function [serum alanine transaminase (ALT), aspartate transaminase (AST), albumin and total bilirubin], oxidative stress [hepatic malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)], inflammatory [hepatic myeloperoxidase (MPO), serum tumor necrosis factor alpha (TNF-α)], relative liver weight, lipid profile [total cholesterol, serum triglycerides, high-density lipoprotein cholesterol (HDL-Ch) and low density lipoprotein cholesterol (LDL-Ch)] were evaluated, supported by liver histopathological study and immunohistochemistry of alpha-smooth muscle actin (α-SMA) in liver sections.Results: Hesperidin significantly decreased hepatic transforming growth factor β1, hydroxyproline, the serum liver function markers of ALT, AST and total bilirubin, the hepatic content of MDA and MPO activity, the serum pro-inflammatory cytokine TNF-α, relative liver weight, and the serum lipid profile markers cholesterol, triglycerides and LDL. On the other hand, Hesperidin significantly increased albumin, the hepatic content of GSH and CAT, and serum lipid profile of LDL. In addition, liver sections obtained from these groups showed marked histopathological and immunohistochemistry of α-SMA improvement.Conclusion: Hesperidin may be promising protective agent against liver fibrosis through improvement of liver function, modulation of the fibrous scar formation, anti-inflammatory and antioxidant potentials.

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