Hepatic inflammation and liver fibrogenesis: a potential target for the treatment of cystic echinococcosis–associated hepatic injury

This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl40.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg) was administered by gavage for 12 days before finishing the CCl4induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, andαSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβexpressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

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The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20071723 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1723 ◽

Cited By ~ 41

Author(s):

Jacopo Baglieri ◽

David Brenner ◽

Tatiana Kisseleva

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Cancer Associated Fibroblasts ◽

Hepatic Inflammation ◽

Therapeutic Approaches ◽

Chronic Liver Injury ◽

Mesenchymal Transition ◽

Liver Fibrogenesis ◽

Tumor Growth And Invasion

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and lacks effective therapeutic approaches. Most HCC develops in the setting of chronic liver injury, hepatic inflammation, and fibrosis. Hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs) are key players in liver fibrogenesis and hepatocarcinogenesis, respectively. CAFs, which probably derive from HSCs, activate into extracellular matrix (ECM)-producing myofibroblasts and crosstalk with cancer cells to affect tumor growth and invasion. In this review, we describe the different components which form the HCC premalignant microenvironment (PME) and the tumor microenvironment (TME), focusing on the liver fibrosis process and the biology of CAFs. We will describe the CAF-dependent mechanisms which have been suggested to promote hepatocarcinogenesis, such as the alteration of ECM, CAF-dependent production of cytokines and angiogenic factors, CAF-dependent reduction of immuno-surveillance, and CAF-dependent promotion of epithelial-mesenchymal transition (EMT). New knowledge of the fibrosis process and the role of CAFs in HCC may pave the way for new therapeutic strategies for liver cancer.

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A combination of pirfenidone and TGF-β inhibition mitigates cystic echinococcosis–associated hepatic injury

Parasitology ◽

10.1017/s0031182021000287 ◽

2021 ◽

pp. 1-39

Author(s):

Erqiang Wang ◽

Zhenyu Liao ◽

Lianghai Wang ◽

Yuan Liao ◽

Xiaodan Xu ◽

...

Keyword(s):

Cystic Echinococcosis ◽

Hepatic Injury

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Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis

Mediators of Inflammation ◽

10.1155/2016/1320365 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Yunan Gao ◽

Hongxiao Yang ◽

Yanbin Fan ◽

Lin Li ◽

Jiahui Fang ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Hepatic Injury ◽

Anticancer Agent ◽

Therapeutic Option ◽

Alanine Transaminase ◽

Oxygen Species ◽

Histopathological Changes ◽

Hepatic Inflammation ◽

Pediatric Cancers ◽

Saline Treatment

Doxorubicin (DOX) remains the most effective anticancer agent which is widely used in several adult and pediatric cancers, but its application is limited for its cardiotoxicity and hepatotoxicity. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for many diseases. In this study, we found that intraperitoneal injection of hydrogen-rich saline (H2 saline) ameliorated the mortality, cardiac dysfunction, and histopathological changes caused by DOX in rats. Meanwhile, serum brain natriuretic peptide (BNP), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), tissue reactive oxygen species (ROS), and malondialdehyde (MDA) levels were also attenuated after H2 saline treatment. What is more, we further demonstrated that H2 saline treatment could inhibit cardiac and hepatic inflammation and apoptosis relative proteins expressions by western blotting test. In conclusion, our results revealed a protective effect of H2 saline on DOX-induced cardiotoxicity and hepatotoxicity in rats by inhibiting inflammation and apoptosis.

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Effects of Nintedanib in an Animal Model of Liver Fibrosis

BioMed Research International ◽

10.1155/2020/3867198 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Lutz Wollin ◽

Dieudonnée Togbe ◽

Bernhard Ryffel

Keyword(s):

Animal Model ◽

Systemic Sclerosis ◽

Hepatic Injury ◽

Preventive Treatment ◽

Hepatic Necrosis ◽

Tissue Inhibitor Of Metalloproteinase ◽

Hepatic Inflammation ◽

Therapeutic Treatment ◽

Internal Organs ◽

Serum Alanine Aminotransferase

Systemic sclerosis can affect multiple internal organs, including the liver and lungs. Nintedanib, an antifibrotic approved for treatment of interstitial lung disease associated with systemic sclerosis, may have activity outside of the lungs. This study explored the effect of preventive and therapeutic nintedanib treatment in a 3-week carbon tetrachloride (CCL4)-induced (500 mg/kg/day twice weekly for 3 weeks) model of hepatic inflammation and fibrosis in C57Bl/6 mice (aged 8 weeks, n=5 per group). Mice also received nintedanib (30 or 60 mg/kg/day) either each day for 21 days (preventive treatment) or from day 7 or day 14 (therapeutic treatment). Preventive nintedanib treatment at both doses significantly reduced CCL4-induced increases in myeloperoxidase (p<0.01), hepatic collagen (p<0.001), and interleukin (IL)-6 (p<0.01) in the liver. Nintedanib also significantly reduced hepatic necrosis (p<0.01 and p<0.05), inflammation (p<0.001 and p<0.05), fibrosis (p<0.001 and p<0.05) and IL-1β (p<0.05 and p<0.001) at both 30 and 60 mg/kg/day, respectively. Therapeutic treatment with nintedanib at 30 and 60 mg/kg/day significantly reduced CCL4-induced serum alanine aminotransferase from day 7 (p<0.05 and p<0.001) and day 14 (p<0.01 and p<0.05), respectively. Increases in tissue inhibitor of metalloproteinase-1 were significantly reduced by nintedanib at 60 mg/kg/day from day 7 only (p<0.001), and nintedanib completely blocked elevation of IL-6 and IL-1β levels regardless of dose or start of treatment (p<0.05–p<0.001). In both the preventive and therapeutic treatment schedules of the study, nintedanib treatment was beneficial in attenuating CCL4-induced pathology and reducing hepatic injury, inflammation, and fibrosis, demonstrating that nintedanib has antifibrotic and anti-inflammatory activity outside of the lungs.

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Liver inflammation before spinal cord injury worsens neuropathology, hepatic injury, metabolic syndrome and locomotor deficits

10.1101/2020.07.15.204578 ◽

2020 ◽

Author(s):

Matthew T. Goodus ◽

Kaitlin E. Carson ◽

Andrew D. Sauerbeck ◽

Priyankar Dey ◽

Anthony N. Alfredo ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Macrophage Activation ◽

Hepatic Injury ◽

Cns Injury ◽

Liver Inflammation ◽

Hepatic Inflammation ◽

Fetuin A ◽

Cord Injury ◽

Locomotor Deficits

ABSTRACTLiver inflammation can enhance acute leukocyte recruitment to sites of central nervous system (CNS) injury. The consequences of hepatic inflammation on recovery after injury, however, are unknown. Here, we hypothesize that liver inflammation at the time of spinal cord injury (SCI) will exacerbate spinal cord pathology and impair recovery. Rats receiving SCI with concomitant liver inflammation had worse intraspinal pathology and greater locomotor deficits than rats with baseline liver inflammation. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia, insulin resistance and adiposity. Circulating and cerebrospinal levels of Fetuin-A were higher in SCI rats with liver inflammation. When microinjected into intact spinal cords, Fetuin-A caused robust macrophage activation, iron accumulation and neuron loss. These studies verify that outcomes from CNS injury are worse if the liver is concomitantly inflamed and implicate Fetuin-A as a potential neuropathological mediator. These novel data suggest hepatic inflammation is a potential clinical target for improving recovery from SCI.

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Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats

British Journal Of Nutrition ◽

10.1017/s000711451200517x ◽

2013 ◽

Vol 110 (3) ◽

pp. 493-499 ◽

Cited By ~ 12

Author(s):

Deniz Güney Duman ◽

Zarife Nigâr Özdemir Kumral ◽

Feriha Ercan ◽

Mustafa Deniz ◽

Güray Can ◽

...

Keyword(s):

Lipid Peroxidation ◽

Hepatic Injury ◽

Histological Analysis ◽

Control Level ◽

Neutrophil Infiltration ◽

Saccharomyces Boulardii ◽

Intestinal Transit ◽

Control Group ◽

Hepatic Inflammation ◽

Antibiotic Associated Diarrhoea

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTX-induced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

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Hepatoprotective effect oftrans-Chalcone on experimentally induced hepatic injury in rats: inhibition of hepatic inflammation and fibrosis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0071 ◽

2016 ◽

Vol 94 (8) ◽

pp. 879-887 ◽

Cited By ~ 17

Author(s):

Harsimran Singh ◽

Shabir Sidhu ◽

Kanwaljit Chopra ◽

M.U. Khan

Keyword(s):

Hepatic Fibrosis ◽

Body Mass ◽

Hepatic Injury ◽

Nitrosative Stress ◽

Hepatoprotective Effect ◽

Histopathological Study ◽

Hepatic Inflammation ◽

Liver Mass ◽

Oxidative And Nitrosative Stress ◽

Percent Change

The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-β1, collagen content), hepatic inflammation (TNF-α), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti-oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent.

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The hydroethanolic Litchi chinensis leaf extract alleviate hepatic injury induced by carbon tetrachloride (CCl4) through inhibition of hepatic inflammation

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.08.076 ◽

2018 ◽

Vol 107 ◽

pp. 929-936 ◽

Cited By ~ 3

Author(s):

Liliani Carolini Thiesen ◽

Maria Luisa de Oliveira Nunes ◽

Christiane Meyre-Silva ◽

Veronica Dávila Pastor ◽

Sérgio Faloni de Andrade ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Leaf Extract ◽

Hepatic Injury ◽

Hepatic Inflammation ◽

Litchi Chinensis

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Fat: Quality, or Quantity? What Matters Most for the Progression of Metabolic Associated Fatty Liver Disease (MAFLD)

Biomedicines ◽

10.3390/biomedicines9101289 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1289

Author(s):

Olga Estévez-Vázquez ◽

Raquel Benedé-Ubieto ◽

Feifei Guo ◽

Beatriz Gómez-Santos ◽

Patricia Aspichueta ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Palm Oil ◽

Fatty Liver Disease ◽

Hepatic Injury ◽

Male Mice ◽

Hepatic Inflammation ◽

High Concentration ◽

Fat Quality ◽

Serum Transaminases

Objectives: Lately, many countries have restricted or even banned transfat, and palm oil has become a preferred replacement for food manufacturers. Whether palm oil is potentially an unhealthy food mainly due to its high content of saturated Palmitic Acid (PA) is a matter of debate. The aim of this study was to test whether qualitative aspects of diet such as levels of PA and the fat source are risk factors for Metabolic Syndrome (MS) and Metabolic Associated Fatty Liver Disease (MAFLD). Methods: C57BL/6 male mice were fed for 14 weeks with three types of Western diet (WD): 1. LP-WD—low concentration of PA (main fat source—corn and soybean oils); 2. HP-WD—high concentration of PA (main fat source—palm oil); 3. HP-Trans-WD—high concentration of PA (mainly transfat). Results: All types of WD caused weight gain, adipocyte enlargement, hepatomegaly, lipid metabolism alterations, and steatohepatitis. Feeding with HP diets led to more prominent obesity, hypercholesterolemia, stronger hepatic injury, and fibrosis. Only the feeding with HP-Trans-WD resulted in glucose intolerance and elevation of serum transaminases. Brief withdrawal of WDs reversed MS and signs of MAFLD. However, mild hepatic inflammation was still detectable in HP groups. Conclusions: HP and HP-Trans-WD play a crucial role in the genesis of MS and MAFLD.

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