A Preliminary Study on the Effect of Hydrogen Gas on Alleviating Early CCl4-Induced Chronic Liver Injury in Rats

As a small-molecule reductant substance, hydrogen gas has an obvious antioxidant function. It can selectively neutralize hydroxyl radicals (•OH) and peroxynitrite (ONOO•) in cells, reducing oxidative stress damage. The purpose of this study was to investigate the effect of hydrogen gas (3%) on early chronic liver injury (CLI) induced by CCl4 and to preliminarily explore the protective mechanism of hydrogen gas on hepatocytes by observing the expression of uncoupling protein 2 (UCP2) in liver tissue. Here, 32 rats were divided into four groups: the control group, CCl4 group, H2 (hydrogen gas) group, and CCl4 + H2 group. The effect of hydrogen gas on early CLI was observed by serological tests, ELISA, hematoxylin and eosin staining, and oil red O staining. Immunohistochemical staining and Western blotting were used to observe the expression of UCP2 in liver tissues. We found that CCl4 can induce significant steatosis in hepatocytes. When the hydrogen gas was inhaled, hepatocyte steatosis was reduced, and the UCP2 expression level in liver tissue was increased. These results suggest that hydrogen gas might upregulate UCP2 expression levels, reduce the generation of intracellular oxygen free radicals, affect lipid metabolism in liver cells, and play a protective role in liver cells.

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Study on the Mechanism of Salvia Miltiorrhiza Polysaccharides in Relieving Liver Injury of Broilers Induced by Fluorophenicol

10.21203/rs.3.rs-179923/v1 ◽

2021 ◽

Author(s):

Yumeng Geng ◽

Chunyu Lu ◽

Guozhong Jin ◽

Shuying Li ◽

Yuqing Cui ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Liver Tissue ◽

Tap Water ◽

Salvia Miltiorrhiza ◽

Serum Levels ◽

Mapk Signaling ◽

Liver Cells ◽

Control Group ◽

Daily Gain

Abstract In order to explore the transcriptomics and proteomics targets and pathways of Salvia miltiorrhiza polysaccharides (SMPs) alleviating florfenicol (FFC)-induced liver injury in broilers,60 1-day-old broilers were randomly divided into 3 groups: control group ( GP1) was fed tap water, FFC model (GP2) was given tap water containing FFC 0.15 g/L, and SMPs treatment group (GP3) was given tap water containing FFC 0.15 g/L and SMPs 5 g/L.Starting from 1 day of age, the drug was administered continuously for 5 days. On the 6th day, blood was collected from the heart and the liver was taken. Then 3 chickens were randomly taken from each group, and their liver tissues were aseptically removed and placed in an enzyme-free tube. Using high-throughput mRNA sequencing and TMT-labeled quantitative proteomics technology, the transcriptome and proteome of the three groups of broiler liver were analyzed respectively. The results of the study showed that the liver tissue morphology of the chicks in the GP1 and GP3 groups was complete, and there were no obvious necrotic cells in the liver cells. The liver tissue cells in the GP2 group showed obvious damage, the intercellular space increased, and the liver cells showed extensive vacuolation and steatosis. Compared with the GP1 group, the daily gain of chicks in the GP2 group was significantly reduced (P < 0.0 5 or P < 0.01). Compared with the GP2 group, the GP3 group significantly increased the daily gain of chicks (P <0.0 5 or P <0.01). Compared with the GP1 group, the serum levels of ALT, AST, liver LPO, ROS and IL-6 in the GP2 group were significantly increased (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4 and IL-10 in the liver were significantly decreased (P < 0.0 5 o r P < 0.01). After SMPs treatment, the serum levels of ALT, AST, liver LPO, ROS and IL-6 were significantly reduced (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4 and IL-10 in the liver were significantly increased (P < 0.0 5 or P < 0.01). There were 380 mRNA and 178 protein differentially expressed between GP2 group and GP3 group. Part of DEGs was randomly selected for QPCR verification, and the expression results of randomly selected FABP1, SLC16A1, GPT2, AACS and other genes were verified by QPCR to be consistent with the sequencing results, which demonstrated the accuracy of transcriptation-associated proteomics sequencing. The results showed that SMPs could alleviate the oxidative stress and inflammatory damage caused by FFC in the liver of chicken and restore the normal function of the liver. SMPs may alleviate the liver damage caused by FFC by regulating the drug metabolism - cytopigment P450, PPAR signaling pathway, MAPK signaling pathway, glutathione metabolism and other pathways.

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Defying death: the hepatocyte's survival kit

Clinical Science ◽

10.1042/cs20040090 ◽

2004 ◽

Vol 107 (1) ◽

pp. 13-25 ◽

Cited By ~ 27

Author(s):

Marieke H. SCHOEMAKER ◽

Han MOSHAGE

Keyword(s):

Cell Death ◽

Liver Injury ◽

Viral Hepatitis ◽

Cell Survival ◽

Apoptotic Cell ◽

Liver Cells ◽

Chronic Liver ◽

Chronic Liver Injury ◽

Cellular Mechanisms ◽

Protective Mechanisms

Acute liver injury can develop as a consequence of viral hepatitis, drug- or toxin-induced toxicity or rejection after liver transplantation, whereas chronic liver injury can be due to long-term exposure to alcohol, chemicals, chronic viral hepatitis, metabolic or cholestatic disorders. During liver injury, liver cells are exposed to increased levels of cytokines, bile acids and oxidative stress. This results in death of hepatocytes. In contrast, stellate cells become active and are resistant against cell death. Eventually, acute and chronic liver injury is followed by loss of liver function for which no effective therapies are available. Hepatocytes are well equipped with protective mechanisms to prevent cell death. As long as these protective mechanisms can be activated, the balance will be in favour of cell survival. However, the balance between cell survival and cell death is delicate and can be easily tipped towards cell death during liver injury. Therefore understanding the cellular mechanisms controlling death of liver cells is of clinical and scientific importance and can lead to the identification of novel intervention targets. This review describes some of the mechanisms that determine the balance between cell death and cell survival during liver diseases. The strict regulation of apoptotic cell death allows therapeutic intervention strategies. In this light, receptor-mediated apoptosis and mitochondria-mediated cell death are discussed and strategies are provided to selectively interfere with these processes.

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Faculty Opinions recommendation of Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718077423.793488042 ◽

2013 ◽

Author(s):

Domenico Alvaro ◽

Vincenzo Cardinale

Keyword(s):

Liver Injury ◽

Chronic Liver ◽

Chronic Liver Injury

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Faculty Opinions recommendation of Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718535300.793521138 ◽

2016 ◽

Author(s):

Malcolm Alison

Keyword(s):

Stem Cell ◽

Liver Injury ◽

Mouse Model ◽

Chronic Liver ◽

Chronic Liver Injury

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Nonselective inhibition of prostaglandin-endoperoxide synthases by naproxen ameliorates acute or chronic liver injury in animals

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2013.10.017 ◽

2014 ◽

Vol 96 (1) ◽

pp. 27-35 ◽

Cited By ~ 3

Author(s):

Ralf Bahde ◽

Sorabh Kapoor ◽

Sanjeev Gupta

Keyword(s):

Liver Injury ◽

Chronic Liver ◽

Chronic Liver Injury ◽

Prostaglandin Endoperoxide

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Ductular reactions provide a structural biliary network to preserve bile drainage in the CDE-model of hepatocellular chronic liver injury

Journal of Hepatology ◽

10.1016/s0168-8278(17)30274-x ◽

2017 ◽

Vol 66 (1) ◽

pp. S6

Author(s):

L.-A. Clerbaux ◽

R. Manco ◽

N. Van Hul ◽

R. Español-Suñer ◽

C. Bouzin ◽

...

Keyword(s):

Liver Injury ◽

Chronic Liver ◽

Chronic Liver Injury ◽

Bile Drainage

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Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00370.2020 ◽

2021 ◽

Author(s):

Tetsuo Takehara ◽

Naoki Mizutani ◽

Hayato Hikita ◽

Yoshinobu Saito ◽

Yuta Myojin ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Injury ◽

Cell Viability ◽

Liver Regeneration ◽

Adaptor Protein ◽

Chronic Liver ◽

Hepatocyte Apoptosis ◽

Chronic Liver Injury ◽

The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

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