scholarly journals STAT3 Promotes Schistosome-Induced Liver Injury by Inflammation, Oxidative Stress, Proliferation and Apoptosis Signal Pathway

2020 ◽  
Author(s):  
Jie Zhao ◽  
Xin Liu ◽  
Yao Chen ◽  
Lin-Shuang Zhang ◽  
Ya-Rong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Signal Pathway ◽  
Granuloma Formation ◽  
Schistosome Infection ◽  
Proliferation And Apoptosis ◽  
Stress Proliferation

Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms that explain the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and signal transducer and activator of transcription 3 (Stat3)flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum. Liver injury, effector molecule levels and RNA transcriptome resequencing of liver were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there has obvious liver fibrosis. A sustained pathological process such as inflammation, oxidative stress, proliferation and apoptosis occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we found the activation of the STAT3 pathway in hepatic injury during S. japonicum infection by RNA transcriptome resequencing. Liver p-STAT3 deficiency alleviated infection-induced liver dysfunction, hepatic granuloma formation and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation and apoptosis are involved in S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.

Aspirin induces autophagy and alleviates liver fibrosis by reducing oxidative stress and inflammation in mice model of chronic liver injury

2020 ◽  
Vol 73 ◽  
pp. S527
Author(s):  
Adil Bhat ◽  
Sudrishti Chaudhary ◽  
Gaurav Yadav ◽  
Anupama Parasar ◽  
Chhagan Bihari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver ◽  
Mice Model ◽  
Chronic Liver Injury

Melittin attenuates liver injury in thioacetamide-treated mice through modulating inflammation and fibrogenesis

2011 ◽  
Vol 236 (11) ◽  
pp. 1306-1313 ◽  
Author(s):  
Ji-Hyun Park ◽  
Yoon-Seup Kum ◽  
Tae-Im Lee ◽  
Soo-Jung Kim ◽  
Woo-Ram Lee ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Liver Inflammation ◽  
Amphipathic Peptide ◽  
Bioactive Component ◽  
Factor Α ◽  
Necrosis Factor

Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. Melittin, the major bioactive component in the venom of honey bee Apis mellifera, is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and proinflammatory properties. However, the molecular mechanisms responsible for the anti-inflammatory activity of melittin have not been elucidated in liver fibrosis. We investigated whether melittin ameliorates liver inflammation and fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co-treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic stellate cells (HSCs) were cultured with tumor necrosis factor α in the absence or presence of melittin. Melittin suppresses the expression of proinflammatory cytokines through the nuclear factor (NF)- κB signaling pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken together, melittin prevents TAA-induced liver fibrosis by inhibiting liver inflammation and fibrosis, the mechanism of which is the interruption of the NF- κB signaling pathway. These results suggest that melittin could be an effective agent for preventing liver fibrosis.

Effects ofUrtica dioicaon oxidative stress, proliferation and apoptosis after partial hepatectomy in rats

2013 ◽  
Vol 31 (5) ◽  
pp. 475-484 ◽  
Author(s):  
Serhat Oguz ◽  
Mehmet Kanter ◽  
Mustafa Erboga ◽  
Toygar Toydemir ◽  
Mustafa Burak Sayhan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Partial Hepatectomy ◽  
Proliferation And Apoptosis ◽  
Stress Proliferation

scholarly journals Impaired endothelial autophagy promotes liver fibrosis by aggravating the oxidative stress response during acute liver injury

2019 ◽  
Vol 70 (3) ◽  
pp. 458-469 ◽  
Author(s):  
Maria Ruart ◽  
Laia Chavarria ◽  
Genís Campreciós ◽  
Nuria Suárez-Herrera ◽  
Carla Montironi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Oxidative Stress Response

scholarly journals Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 976
Author(s):  
Chongshan Dai ◽  
Hui Li ◽  
Yang Wang ◽  
Shusheng Tang ◽  
Tony Velkov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Protective Effect ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Liver Tissues

This study investigates the protective effect of baicalein on carbon tetrachloride (CCl4)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl4 injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl4 exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl4-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl4. In vitro, baicalein treatment improved CCl4 -induced decreases of cell viabilities and knockdown of Nrf2 and arachidonate 12-lipoxygenase (ALOX12) genes partly abolished the protective effect of baicalein on CCl4 -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl4-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.

scholarly journals Attenuation of acute and chronic liver injury in rats by iron-deficient diet

2008 ◽  
Vol 294 (2) ◽  
pp. R311-R320 ◽  
Author(s):  
Kohji Otogawa ◽  
Tomohiro Ogawa ◽  
Ryoko Shiga ◽  
Kazuki Nakatani ◽  
Kazuo Ikeda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Liver Injuries ◽  
Iron Deficient

Oxidative stress due to iron deposition in hepatocytes or Kupffer cells contributes to the initiation and perpetuation of liver injury. The aim of this study was to clarify the association between dietary iron and liver injuries in rats. Liver injury was initiated by the administration of thioacetamide or ligation of the common bile duct in rats fed a control diet (CD) or iron-deficient diet (ID). In the acute liver injury model induced by thioacetamide, serum levels of aspartate aminotransferase and alanine aminotransferase, as well as hepatic levels of lipid peroxide and 4-hydroxynonenal, were significantly decreased in the ID group. The expression of 8-hydroxydeoxyguanosine and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling positivity showed a similar tendency. The expression of interleukin-1β and monocyte chemotactic protein-1 mRNA was suppressed in the ID group. In liver fibrosis induced by an 8-wk thioacetamide administration, ID suppressed collagen deposition and smooth muscle α-actin expression. The expressions of collagen 1A2, transforming growth factor β, and platelet-derived growth factor receptor β mRNA were all significantly decreased in the ID group. Liver fibrosis was additionally suppressed in the bile-duct ligation model by ID. In culture experiments, deferoxamine attenuated the activation process of rat hepatic stellate cells, a dominant producer of collagen in the liver. In conclusion, reduced dietary iron is considered to be beneficial in improving acute and chronic liver injuries by reducing oxidative stress. The results obtained in this study support the clinical usefulness of an iron-reduced diet for the improvement of liver disorders induced by chronic hepatitis C and alcoholic/nonalcoholic steatohepatitis.

scholarly journals Astaxanthin Prevents Diet-Induced NASH Progression by Shaping Intrahepatic Immunity

2021 ◽  
Vol 22 (20) ◽  
pp. 11037
Author(s):  
Ming Yang ◽  
Eric T. Kimchi ◽  
Kevin F. Staveley-O’Carroll ◽  
Guangfu Li
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Stellate Cell ◽  
In Vitro Studies ◽  
Alcoholic Fatty Liver ◽  
Duct Ligation

Dietary change leads to a precipitous increase in non-alcoholic fatty liver disease (NAFLD) from simple steatosis to the advanced form of non-alcoholic steatohepatitis (NASH), affecting approximately 25% of the global population. Although significant efforts greatly advance progress in clarifying the pathogenesis of NAFLD and identifying therapeutic targets, no therapeutic agent has been approved. Astaxanthin (ASTN), a natural antioxidant product, exerts an anti-inflammation and anti-fibrotic effect in mice induced with carbon tetrachloride (CCl4) and bile duct ligation (BDL); thus, we proposed to further investigate the potential effect of ASTN on a diet-induced mouse NASH and liver fibrosis, as well as the underlying cellular and molecular mechanisms. By treating pre-development of NASH in mice induced with a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD), we have demonstrated that oral administration ASTN preventively ameliorated NASH development and liver fibrosis by modulating the hepatic immune response, liver inflammation, and oxidative stress. Specifically, ASTN treatment led to the reduction in liver infiltration of monocyte-derived macrophages, hepatic stellate cell (HSC) activation, oxidative stress response, and hepatocyte death, accompanied by the decreased hepatic gene expression of proinflammatory cytokines such as TNF-α, TGF-β1, and IL-1β. In vitro studies also demonstrated that ASTN significantly inhibited the expression of proinflammatory cytokines and chemokine CCL2 in macrophages in response to lipopolysaccharide (LPS) stimulation. Overall, in vivo and in vitro studies suggest that ASTN functions as a promising therapeutic agent to suppress NASH and liver fibrosis via modulating intrahepatic immunity.

scholarly journals Methane-Rich Saline Counteracts Cholestasis-Induced Liver Damage via Regulating the TLR4/NF-κB/NLRP3 Inflammasome Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zeyu Li ◽  
Dongdong Chen ◽  
Yifan Jia ◽  
Yang Feng ◽  
Cong Wang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Inflammatory Cells ◽  
Protective Mechanism ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Associated Proteins ◽  
Anti Inflammatory ◽  
Cholestatic Liver Injury

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.

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