scholarly journals Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yaru Xue ◽  
Qiangqiang Deng ◽  
Qingli Zhang ◽  
Zhenghua Ma ◽  
Binfan Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Nordihydroguaiaretic Acid ◽  
Hepatic Inflammation ◽  
Cpla2 Activation ◽  
Inflammatory Processes ◽  
Mrna And Protein Expression ◽  
Lox Inhibitors ◽  
Jnk Activation

AbstractArachidonic acid (AA) signaling pathway is an important constituent of inflammatory processes. In our previous study, it was found that dihydro-stilbene gigantol relieved hepatic inflammation in mice with CCl4-induced acute liver injury. This study aimed to investigate the involvement of arachidonate metabolic cascade in this process. Our results showed CCl4 activated AA metabolism with the evidence of cPLA2 phosphorylation, which was dependent on the MAPK/JNK activation. Pretreatment with JNK inhibitor SU3327 or gigantol abolished the cPLA2 activation, along with the attenuation of liver damage. Besides, gigantol markedly decreased immune cells activation. Metabolomic analysis revealed that gigantol universally reversed the upregulation of major AA metabolites in injured mouse livers induced by CCl4, especially 12-hydroxyeicosatetraenoic acid (12-HETE). Gigantol also decreased the mRNA and protein expression of platelet-, and leukocyte-type 12-lipoxxygenase (LOX) in the liver. Furthermore, pan-LOX inhibitor nordihydroguaiaretic acid (NDGA) and specific 12-LOX inhibitors baicalein and ML351 attenuated the liver injury to the same extent as gigantol. Overall, our study elucidated a comprehensive profile of AA metabolites during hepatic inflammation caused by CCl4, highlighting the role of 12-LOX-12-HETE pathway in this process. And gigantol alleviated liver inflammation partly through inhibiting the JNK/cPLA2/12-LOX pathway.

scholarly journals The role of non-steroidal anti-inflammatory drugs in acute liver injury.

BMJ ◽  
1992 ◽  
Vol 305 (6858) ◽  
pp. 865-868 ◽  
Author(s):  
L. A. Garcia Rodriguez ◽  
S. Perez Gutthann ◽  
A. M. Walker ◽  
L. Lueck
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

scholarly journals Role of procoagulant microparticles in mediating complications and outcome of acute liver injury/acute liver failure

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 304-313 ◽  
Author(s):  
R. Todd Stravitz ◽  
Regina Bowling ◽  
Robert L. Bradford ◽  
Nigel S. Key ◽  
Sam Glover ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury

The role of Cell-free DNA as a marker to predict acute liver injury in rats

2013 ◽  
Vol 30 ◽  
pp. 194-194
Author(s):  
B. F. Gruenbaum ◽  
M. Boyko ◽  
A. Leibowitz ◽  
R. Kutz ◽  
A. Zlotnik
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury

2010 ◽  
Vol 89 (3) ◽  
pp. 433-442 ◽  
Author(s):  
Kiminori Kimura ◽  
Satoshi Sekiguchi ◽  
Seishu Hayashi ◽  
Yukiko Hayashi ◽  
Tsunekazu Hishima ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Cell ◽  
Acute Liver Injury ◽  
Interleukin 18 ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

scholarly journals Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziheng Yang ◽  
Jie Zhang ◽  
Yan Wang ◽  
Jing Lu ◽  
Quan Sun
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Caveolin 1 ◽  
Hepatic Macrophages ◽  
M1 Phenotype

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.

scholarly journals The role of urea on the prognosis of severe acute liver injury and acute liver failure

2020 ◽  
Vol 73 ◽  
pp. S217-S218
Author(s):  
Ana Craciun ◽  
Carolina Simões ◽  
Ana Valente ◽  
Cilénia Baldaia ◽  
Carlos Freitas ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Liver Injury
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