Indoline derivatives mitigate liver damage in a mouse model of acute liver injury

2017 ◽  
Vol 69 (5) ◽  
pp. 894-902 ◽  
Author(s):  
Efrat Finkin-Groner ◽  
Shlomi Finkin ◽  
Shani Zeeli ◽  
Marta Weinstock
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Liver Damage ◽  
Acute Liver Injury

scholarly journals Characterization and Evaluation of HGF-Loaded PLGA Nanoparticles in a CCl4-Induced Acute Liver Injury Mouse Model

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Chuxi Lin ◽  
Xueer Wang ◽  
Nuyun Liu ◽  
Qing Peng ◽  
Yang Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Acute Liver Injury ◽  
Redox Homeostasis ◽  
Plga Nanoparticles ◽  
Physical Characteristics ◽  
Sod Activity ◽  
Therapeutic Benefits ◽  
Antioxidant Proteins ◽  
Drug Free

Liver injury can be caused by various harmful factors since the liver is considered the key organ for detoxifying endogenous and exogenous substances. Hepatocyte growth factor (HGF) can regulate redox homeostasis through the expression of antioxidant proteins when the liver is under injury. However, HGF is easily degraded. In this study, we produced three kinds of HGF-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles with an initial addition of 2 μg HGF (NPs-HGF-2 μg), 4 μg HGF (NPs-HGF-4 μg), and drug-free nanoparticles (NPs) using the W/O/W emulsion-solvent evaporation method in accordance with our patent. The morphology and physical characteristics were analyzed, and effects of HGF-loaded PLGA nanoparticles on a CCl4-induced acute liver injury mouse model were investigated and compared with HGF solutions. We observed that the morphology and the physical characteristics of the nanoparticles were almost the same, with similar sizes, polydispersity, and zeta potential. HGF-loaded PLGA nanoparticles maintained higher HGF concentrations for a longer period of time in blood and liver tissues. HGF-loaded PLGA nanoparticles increased the SOD activity and GPX levels, decreased the MDA levels in the liver, reduced the necrotic areas of the liver, and decreased the levels of AST, ALT, ALP, T-BIL, BUN, and Scr in blood. In conclusion, our technique for preparing HGF-loaded PLGA nanoparticles was stable and the products were of good quality. HGF-loaded PLGA nanoparticles could provide greater therapeutic benefits on CCl4-induced acute liver injury, including antilipid peroxidation and a reduction in indicator enzymes of liver injury.

MicroRNA-29a protects against acute liver injury in a mouse model of obstructive jaundice via inhibition of the extrinsic apoptosis pathway

APOPTOSIS ◽  
2013 ◽  
Vol 19 (1) ◽  
pp. 30-41 ◽  
Author(s):  
Mao-Meng Tiao ◽  
Feng-Sheng Wang ◽  
Li-Tung Huang ◽  
Jiin-Haur Chuang ◽  
Ho-Chang Kuo ◽  
...  
Keyword(s):  
Liver Injury ◽  
Obstructive Jaundice ◽  
Mouse Model ◽  
Acute Liver Injury ◽  
Apoptosis Pathway ◽  
Extrinsic Apoptosis

Involvement of Th2 cytokines in the mouse model of flutamide-induced acute liver injury

2011 ◽  
Vol 32 (10) ◽  
pp. 815-822 ◽  
Author(s):  
Satonori Higuchi ◽  
Masanori Kobayashi ◽  
Azusa Yano ◽  
Koichi Tsuneyama ◽  
Tatsuki Fukami ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Acute Liver Injury ◽  
Th2 Cytokines

scholarly journals Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xichuan Wei ◽  
Chuanhong Luo ◽  
Yanan He ◽  
Haozhou Huang ◽  
Fei Ran ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Protein Expression ◽  
Acute Liver Injury ◽  
Quinone Oxidoreductase ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
The Impact

Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined.Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting.Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1.Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

scholarly journals Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury

2021 ◽  
Vol 13 (597) ◽  
pp. eaba8146
Author(s):  
Anissa A. Widjaja ◽  
Jinrui Dong ◽  
Eleonora Adami ◽  
Sivakumar Viswanathan ◽  
Benjamin Ng ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Liver Damage ◽  
Therapeutic Target ◽  
Nuclear Antigen ◽  
Autocrine Loop ◽  
Nadph Oxidase 4 ◽  
Adult Mice ◽  
Extracellular Signal ◽  
Dependent Cell

Acetaminophen (N-acetyl-p-aminophenol; APAP) toxicity is a common cause of liver damage. In the mouse model of APAP-induced liver injury (AILI), interleukin 11 (IL11) is highly up-regulated and administration of recombinant human IL11 (rhIL11) has been shown to be protective. Here, we demonstrate that the beneficial effect of rhIL11 in the mouse model of AILI is due to its inhibition of endogenous mouse IL11 activity. Our results show that species-matched IL11 behaves like a hepatotoxin. IL11 secreted from APAP-damaged human and mouse hepatocytes triggered an autocrine loop of NADPH oxidase 4 (NOX4)–dependent cell death, which occurred downstream of APAP-initiated mitochondrial dysfunction. Hepatocyte-specific deletion of Il11 receptor subunit alpha chain 1 (Il11ra1) in adult mice protected against AILI despite normal APAP metabolism and glutathione (GSH) depletion. Mice with germline deletion of Il11 were also protected from AILI, and deletion of Il1ra1 or Il11 was associated with reduced c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinase (ERK) activation and quickly restored GSH concentrations. Administration of a neutralizing IL11RA antibody reduced AILI in mice across genetic backgrounds and promoted survival when administered up to 10 hours after APAP. Inhibition of IL11 signaling was associated with the up-regulation of markers of liver regenerations: cyclins and proliferating cell nuclear antigen (PCNA) as well as with phosphorylation of retinoblastoma protein (RB) 24 hours after AILI. Our data suggest that species-matched IL11 is a hepatotoxin and that IL11 signaling might be an effective therapeutic target for APAP-induced liver damage.

P.149 HEPATOPROTECTIVE EFFECT OF INTERLEUKIN (IL-) 25 IN A MOUSE MODEL OF ACUTE LIVER INJURY

2010 ◽  
Vol 42 ◽  
pp. S155-S156
Author(s):  
M. Sarra ◽  
R. Bernardini ◽  
A. Rizzo ◽  
R. Caruso ◽  
C. Stolfi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Acute Liver Injury ◽  
Hepatoprotective Effect

scholarly journals Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yange Liu ◽  
Juan Wang ◽  
Lanzhou Li ◽  
Wenji Hu ◽  
Yidi Qu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Mouse Model ◽  
Caspase 3 ◽  
Acute Liver Injury ◽  
Nuclear Factor ◽  
Related Factors ◽  
Inflammatory Infiltration ◽  
Hepatoprotective Effects ◽  
Underlying Mechanisms

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

scholarly journals Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

2019 ◽  
Vol 116 (18) ◽  
pp. 9125-9134 ◽  
Author(s):  
Min-Jung Park ◽  
Louis G. D’Alecy ◽  
Michelle A. Anderson ◽  
Venkatesha Basrur ◽  
Yongjia Feng ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Half Life ◽  
Fas Ligand ◽  
Urea Cycle ◽  
Acute Liver Injury ◽  
Carbamoyl Phosphate ◽  
Human Bile ◽  
Cycle Enzyme ◽  
Short Half Life

Carbamoyl phosphate synthetase-1 (CPS1) is the major mitochondrial urea cycle enzyme in hepatocytes. It is released into mouse and human blood during acute liver injury, where is has a short half-life. The function of CPS1 in blood and the reason for its short half-life in serum are unknown. We show that CPS1 is released normally into mouse and human bile, and pathologically into blood during acute liver injury. Other cytoplasmic and mitochondrial urea cycle enzymes are also found in normal mouse bile. Serum, bile, and purified CPS1 manifest sedimentation properties that overlap with extracellular vesicles, due to the propensity of CPS1 to aggregate despite being released primarily as a soluble protein. During liver injury, CPS1 in blood is rapidly sequestered by monocytes, leading to monocyte M2-polarization and homing to the liver independent of its enzyme activity. Recombinant CPS1 (rCPS1), but not control r-transferrin, increases hepatic macrophage numbers and phagocytic activity. Notably, rCPS1 does not activate hepatic macrophages directly; rather, it activates bone marrow and circulating monocytes that then home to the liver. rCPS1 administration prevents mouse liver damage induced by Fas ligand or acetaminophen, but this protection is absent in macrophage-deficient mice. Moreover, rCPS1 protects from acetaminophen-induced liver injury even when given therapeutically after injury induction. In summary, CPS1 is normally found in bile but is released by hepatocytes into blood upon liver damage. We demonstrate a nonenzymatic function of CPS1 as an antiinflammatory protective cytokine during acute liver injury.

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