scholarly journals Red Quinoa Bran Extracts Protects against Carbon Tetrachloride-Induced Liver Injury and Fibrosis in Mice via Activation of Antioxidative Enzyme Systems and Blocking TGF-β1 Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 395 ◽  
Author(s):  
Ting-An Lin ◽  
Bo-Jun Ke ◽  
Cheng-Shih Cheng ◽  
Jyh-Jye Wang ◽  
Bai-Luh Wei ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Agricultural Waste ◽  
Ethanol Extract ◽  
Inflammatory Factor ◽  
High Concentration ◽  
Necrosis Factor Alpha ◽  
Tgf Β1

The late stages of liver fibrosis are considered to be irreversible. Red quinoa (Chenopodium formosanum Koidz), a traditional food for Taiwanese aborigines, was gradually developed as a novel supplemental food due to high dietary fibre and polyphenolic compounds. Its bran was usually regarded as the agricultural waste, but it contained a high concentration of rutin known as an antioxidant and anti-inflammatory agent. This study is to explore the effect of red quinoa bran extracts on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis. BALB/c mice were intraperitoneally injected CCl4 to induce liver fibrosis and treated with red quinoa whole seed powder, bran ethanol extracts, bran water extracts, and rutin. In the results, red quinoa powder provided more protection than rutin against CCl4-induced oxidative stress, pro-inflammatory factor expression and fibrosis development. However, the bran ethanol extract with high rutin content provided the most liver protection and anti-fibrosis effect via blocking the tumor necrosis factor alpha (TNF-α)/interleukin 6 (IL-6) pathway and transforming growth factor beta 1 (TGF-β1) pathway.

scholarly journals Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Manal G. Mahmoud ◽  
Mohsen S. Asker ◽  
Mohamed E. El Awady ◽  
Amal I. Hassan ◽  
Nadia A. R. Zaharan ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Periodate Oxidation ◽  
Hepatic Tissue ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Glutamyl Transferase ◽  
Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

scholarly journals Sedum sarmentosum Total Flavonoids Alleviate Schistosomiasis-Induced Liver Fibrosis by Altering TGF-β1 and Smad7 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Peng-chun Yang ◽  
Wei-zhe Bai ◽  
Jing Wang ◽  
Cai-hua Yan ◽  
Wei-feng Huang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Schistosomiasis Japonica ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Tgf Β1 ◽  
Liver Tissues

Objectives. Schistosomiasis is a parasitic disease that affects over 142 million people worldwide. The main causes of death of schistosomiasis include liver granuloma and secondary hepatic cirrhosis resulting from severe fibrosis. Despite intensive research, controlling liver fibrosis associated with schistosomiasis remains challenging. Sedum sarmentosum total flavonoid (SSTF) is a promising agent to reduce liver fibrosis with an unknown mechanism. Thus, the objectives of this study are to validate its effect on the liver fibrosis caused by schistosomiasis and to explore the underlying molecular mechanism. Methods. Sixty male Sprague-Dawley rats were randomly divided into six groups: one group of normal control and five groups of liver fibrosis induced by schistosomiasis japonica with or without SSTF or colchicine treatment, the latter serving as the positive control. Liver tissues from each animal were harvested to observe the degree and grade of hepatic fibrosis. We also measured the expression of transforming growth factor-beta 1 (TGF-β1) and Smad7 using RT-qPCR, Western blot, and immunohistochemistry. Results. Compared with the untreated model group, groups treated with SSTF at all three tested doses had significantly reduced hepatic fibrosis ( P < 0.05 ). Each dose of SSTF also significantly reduced TGF-β1 protein expression and mRNA levels in the liver tissues ( P < 0.05 ). In contrast, the middle and high doses of SSTF significantly increased Smad7 protein expression and mRNA levels ( P < 0.05 ). Immunohistochemistry showed that each dose of SSTF reduced TGF-β1 protein expression ( P < 0.05 ). Conclusion. Our results demonstrated that SSTF alleviated schistosomiasis japonica-induced hepatic fibrosis by inhibiting the TGF-β1/Smad7 pathway.

scholarly journals Therapeutic Effect of Dunaliella salina Microalgae on Thioacetamide- (TAA-) Induced Hepatic Liver Fibrosis in Rats: Role of TGF-β and MMP9

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Farouk K. El-Baz ◽  
Abeer Salama ◽  
Rania A. A. Salama
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Dunaliella Salina ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Elevated Serum ◽  
Serum Levels ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Liver Histopathology

Liver fibrosis represents a serious global health-care problem and is the outcome of many chronic liver diseases, cirrhosis, hepatitis, and toxin accumulation. The present study aimed to evaluate the antifibrotic curative effect of Dunaliella salina (D. salina) on thioacetamide- (TAA-) induced liver fibrosis in rats. Liver fibrosis was induced by TAA (200mg/kg; i.p.) twice per week for 6 weeks. D. salina was given orally (100 and 200 mg/kg) and silymarin was given orally (100 mg/kg) daily, for 4 weeks after TAA. Serum transaminase activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA significantly (p<0.05) elevated serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and serum levels of total bilirubin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β) with a reduction in albumin. In addition, TAA increased hepatic contents of collagen I, a-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase (TIMP-1), reduced matrix metalloproteinase 9 (MMP9), and finally produced marked degeneration and fibrosis of hepatocytes. Treatment with D. salina or silymarin improved the histological feature of hepatocytes and ameliorated the deleterious effects of TAA in a dose-dependent manner. Based on these results, it could be concluded that the use of D. salina could be assigned for liver fibrosis treatment via its anti-inflammatory and antifibrotic properties.

Effect of intestinal colonisation by two Lactobacillus strains on the immune response of gnotobiotic mice

2014 ◽  
Vol 5 (4) ◽  
pp. 409-419 ◽  
Author(s):  
R.S. Steinberg ◽  
M. Lima ◽  
N.L. Gomes de Oliveira ◽  
A. Miyoshi ◽  
J.R. Nicoli ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Necrosis Factor Alpha ◽  
Interleukin 5 ◽  
Germ Free ◽  
Intestinal Colonisation ◽  
Tnf Α ◽  
Tgf Β1 ◽  
Intragastric Gavage

The effect of intestinal colonisation on the immune system was investigated in germ-free mice monoassociated with Lactobacillus strains isolated from calf faeces. Single doses of Lactobacillus acidophilus L36 or Lactobacillus salivarius L38 were administered to germ-free mice by intragastric gavage. Ten days later, the mice were euthanised. Gene expression levels of interleukin 5 (IL-5), IL-6, IL-10, IL-12b, IL-17a, gamma interferon (IFN-γ), transforming growth factor beta 1 (TGF-β1), and tumour necrosis factor alpha (TNF-α) were quantified in segments of the small and large intestines by real time quantitative polymerase chain reaction. All the mice were colonised rapidly after Lactobacillus administration with intestinal counts ranging from 6.53 to 8.26 log cfu/g. L. acidophilus L36 administration increased the expression of cytokines involved with the Th2 (IL-5, IL-6 and TGF-β1) and Th17 (IL-17a, TNF-α and IL-6) inflammatory response, whereas L. salivarius L38 appeared to stimulate a pattern of less diversified cytokines in the intestine. Intragastric gavage of L. acidophilus L36 and L. salivarius L38 induced similar levels of colonisation in the digestive tracts of germ-free mice but stimulated different immune responses in the intestinal mucosa. The different immunomodulation patterns might facilitate the potential use of these lactobacilli as probiotics to treat distinct pathological conditions, for example protection against Citrobacter rodentium infection by stimulating IL-17 production.

scholarly journals Hyaluronic acid and TGF-β1 in dogs with hepatobiliary diseases

2018 ◽  
Vol 87 (3) ◽  
pp. 231-240 ◽  
Author(s):  
Václav Ceplecha ◽  
Kristína Řeháková ◽  
Corinne Lendon ◽  
Pavel Proks ◽  
Miša Škorič ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Vascular Anomaly ◽  
Non Invasive ◽  
Portosystemic Shunts ◽  
Advanced Liver Fibrosis ◽  
Tgf Β1

The aim of the study was to assess serum hyaluronic acid (HA) and transforming growth factor beta 1 (TGF-β1) concentrations: 1) to differentiate hepatic fibrosis from other forms of liver disease, and 2) for the non-invasive staging of canine liver fibrosis. We also evaluated the association between serum HA concentration and the size of the shunt vessel as an indirect marker of decreased liver clearance in patients with single congenital vascular anomaly. Forty-one healthy client-owned dogs and forty dogs diagnosed with hepatobiliary disease were enrolled in the prospective study. Patients were divided into 4 subgroups: 1) congenital portosystemic shunts (CPSS); 2) parenchymal diseases (a. mild and moderate fibrosis, b. advanced fibrosis and cirrhosis); 3) hepatic neoplasia; 4) biliary tract disorders based on thorough clinical, ultrasound and histopathological examination. Serum HA and TGF-β1 concentrations were measured using ELISA. The HA concentration was significantly increased in patients with advanced liver fibrosis/cirrhosis (P < 0.001) and CPSS (P < 0.001) compared to healthy dogs. Using a cut-off HA concentration of 135.94 ng/ml, the sensitivity and specificity for diagnosis for advanced liver fibrosis/cirrhosis was 100% (95% CI, 50.6–100) and 90.8% (95% CI, 81.6–95.7), respectively. The TGF-β1 levels did not significantly differ among groups (P = 0.180). Negligible correlation was found between serum HA concentration and the size of portosystemic shunt vessel (rs = 0.07; P = 0.831). These findings suggest that serum HA concentration is a potential non-invasive biomarker for advanced liver fibrosis and/or cirrhosis in dogs. The utility of measuring serum concentration of TGF-β1 for diagnosing canine liver fibrosis was not supported.

Hepatoprotective effect of Linagliptin against liver fibrosis induced by carbon tetrachloride in mice

2020 ◽  
Author(s):  
Maaly Abd Elmaaboud ◽  
Haidy Khattab ◽  
Shahinaz Shalaby
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Biochemical Parameters ◽  
Transforming Growth Factor ◽  
Corn Oil ◽  
Smooth Muscle Actin ◽  
Mammalian Target Of Rapamycin ◽  
Metavir Score ◽  
Tgf Β1

The current study aimed to investigate linagliptin for its potential role in the prevention of liver fibrosis progression. Balb-C mice were randomly allocated into 5 groups (10 each), (1) control, (2) mice were injected intraperitoneally with 50 μl carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 μl /g 3 times a week for 4 weeks, (3) linagliptin was orally administered in a dose of 10 mg/kg/day simultaneously with CCl4, (4) silymarin was orally in a dose of 200 mg/kg/day concomitantly with CCl4, (5) linagliptin only. Hepatic injury was manifested in CCl4 group by elevation of biochemical parameters; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of α-smooth muscle actin (α-SMA), also, increased liver tissue oxidative stress parameters, transforming growth factor-β1 (TGF-β1) and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis; evident histopathologically with reduced METAVIR score and α-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-β1, and mTOR, this was associated with improvement of serum biochemical parameters; ALT and AST. In conclusion, linagliptin might help to protect the liver against persistent injury-related consequences.

Cryptolepine derivative-6h inhibits liver fibrosis in TGF-β1-induced HSC-T6 cells by targeting the Shh pathway

2016 ◽  
Vol 94 (9) ◽  
pp. 987-995 ◽  
Author(s):  
Ying-Hua He ◽  
Zeng Li ◽  
Ming-Ming Ni ◽  
Xing-Yan Zhang ◽  
Ming-Fang Li ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
African Countries ◽  
Shh Pathway ◽  
Tgf Β1

Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-β1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-β1-induced HSC-T6 cells.

scholarly journals MicroRNA-34a Promotes EMT and Liver Fibrosis in Primary Biliary Cholangitis by Regulating TGF-β1/smad Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ying Pan ◽  
Jing Wang ◽  
Lan He ◽  
Fengchun Zhang
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Peripheral Blood ◽  
Transforming Growth Factor ◽  
Primary Biliary Cholangitis ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Growth Factor Beta ◽  
Tgf Β1

Background and Aims. Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease. We found microRNA-34a (miR-34a), as the downstream gene of p53, was overexpressed in some of fibrogenic diseases. In this study, we sought to explore whether miR-34a plays a role in the fibrosis of PBC. Methods. The peripheral blood of PBC patients and controls was collected to analyze the level of miR-34a. Human intrahepatic biliary epithelial cells (HIBEC) were cultured. The expression of miR-34a was regulated by miR-34a mimics and inhibitor. The biomarkers of epithelium-mesenchymal transition (EMT), fibrogenesis, inflammation, and transforming growth factor- (TGF-) β1/smad pathway were analyzed. Results. We found that miR-34a was overexpressed in the peripheral blood in PBC patients. In vitro, overexpressed miR-34a increased the EMT and fibrogenesis activity of HIBEC. Transforming growth factor-beta type 1 receptor (TβR1), TGF-β1, and p-smad2/3 were upregulated by miR-34a. Inflammatory factors such as IL-6 and IL-17 were also upregulated. Finally, we showed that miR-34a promoted EMT and liver fibrosis in PBC by targeting the TGF-β1/smad pathway antagonist transforming growth factor-beta-induced factor homeobox 2 (TGIF2). Conclusions. Our findings show that miR-34a plays an important role in the EMT and fibrosis of PBC through the TGF-β1/smad pathway by targeting TGIF2. This study suggests that miR-34a may be a new marker of fibrogenesis in PBC. Inhibition of miR-34a may be a promising strategy in treating PBC and improving the prognosis of the disease.

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