scholarly journals Maresin-1 Prevents Liver Fibrosis by Targeting Nrf2 and NF-κB, Reducing Oxidative Stress and Inflammation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3406
Author(s):  
María José Rodríguez ◽  
Matías Sabaj ◽  
Gerardo Tolosa ◽  
Francisca Herrera Vielma ◽  
María José Zúñiga ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Activity Index ◽  
Antioxidant Response ◽  
Treated Group ◽  
Hepatocyte Proliferation ◽  
Sprague Dawley ◽  
Ki 67 ◽  
Maresin 1 ◽  
Anti Inflammatory

Liver fibrosis is a complex process characterized by the excessive accumulation of extracellular matrix (ECM) and an alteration in liver architecture, as a result of most types of chronic liver diseases such as cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Maresin-1 (MaR1) is derivative of ω-3 docosahexaenoic acid (DHA), which has been shown to have pro-resolutive and anti-inflammatory effects. We tested the hypothesis that the application of MaR1 could prevent the development of fibrosis in an animal model of chronic hepatic damage. Sprague-Dawley rats were induced with liver fibrosis by injections of diethylnitrosamine (DEN) and treated with or without MaR1 for four weeks. In the MaR1-treated animals, levels of AST and ALT were normalized in comparison with DEN alone, the hepatic architecture was improved, and inflammation and necrotic areas were reduced. Cell proliferation, assessed by the mitotic activity index and the expression of Ki-67, was increased in the MaR1-treated group. MaR1 attenuated liver fibrosis and oxidative stress was induced by DEN. Plasma levels of the pro-inflammatory mediators TNF-α and IL-1β were reduced in MaR1-treated animals, whereas the levels of IL-10, an anti-inflammatory cytokine, increased. Interestingly, MaR1 inhibited the translocation of the p65 subunit of NF-κB, while increasing the activation of Nrf2, a key regulator of the antioxidant response. Finally, MaR1 treatment reduced the levels of the pro-fibrotic mediator TGF-β and its receptor, while normalizing the hepatic levels of IGF-1, a proliferative agent. Taken together, these results suggest that MaR1 improves the parameters of DEN-induced liver fibrosis, activating hepatocyte proliferation and decreasing oxidative stress and inflammation. These results open the possibility of MaR1 as a potential therapeutic agent in fibrosis and other liver pathologies.

scholarly journals Mesenchymal Stromal Cells Suppress Hepatic Fibrosis Via Modulating the Expression of Fibronectin and Integrin and Inhibiting DNA Fragmentation in Rats

2021 ◽  
Author(s):  
sherine ibrahim ◽  
ahmed fayez ◽  
ahmed maher
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Dna Fragmentation ◽  
Inflammatory Markers ◽  
Treated Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Stromal Stem Cells

IntroductionLiver fibrosis is currently the 11th most common cause of death worldwide. Because of self-renewal, available sources for isolation, and high differentiation properties, multipotent mesenchymal stromal stem cells are suggested to be potential tool for treatment of liver fibrosis. In this study, we examined the anti-fibrotic and anti-inflammatory activity of bone marrow-derived multipotent mesenchymal stromal stem cells (MSCs) on liver fibrosis induced by carbon tetrachloride on rats relative to silymarin as a standard drug.Material and methodsThis study was performed on 40 male Sprague Dawley rats divided into 4 groups of ten rats each: Group 1 served as controls, Group 2 served as CCl4 (diseased) group, Group 3 served as silymarin treated group and Group 4 served as MSCs treated group. Liver fibrosis was assessed by determination of liver markers and fibrogenesis related genes together with the anti-inflammatory markers in the liver tissue. DNA fragmentation was assessed by Comet assay.ResultsMSCs treatment reduced all liver fibrosis markers as well as the oxidative stress and inflammatory markers. Additionally, MSCs reduced the expression of integrins and fibronectin compared with the control group as well as decreasing DNA fragmentation.ConclusionsTreatment by MSCs significantly ameliorates liver fibrosis in rats. This amelioration was a result of acting on both the anti-inflammatory and anti-fibrotic activity of hepatocytes.

scholarly journals Vinpocetine attenuates thioacetamide-induced liver fibrosis in rats

2020 ◽  
pp. 096032712094745
Author(s):  
Ahmed A Elnfarawy ◽  
Asmaa E Nashy ◽  
Alaa M Abozaid ◽  
Ibrahim F Komber ◽  
Rawan H Elweshahy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Fibrosis ◽  
Vinca Alkaloid ◽  
Sprague Dawley ◽  
Ki 67 ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Synthetic Derivative

Liver fibrosis is associated with increased mortality and morbidity. However, there is not effective treatment so far. Vinpocetine (Vinpo) is a synthetic derivative of vinca alkaloid vincamine. Limited previous reports have shown some beneficial effects of Vinpo in different organ fibrosis, but the ability of Vinpo to inhibit liver fibrosis induced by thioacetamide (TAA) has not been reported, that is why we investigate the potential ability of this vinca alkaloid derivative to attenuate liver fibrosis. Hepatic fibrosis was induced in male Sprague Dawley rats by TAA (200 mg/kg; ip; 3 times/week) for 6 weeks. Daily treatments with Vinpo (10–20 mg/kg/day; orally) ameliorated TAA-induced hepatic oxidative stress and histopathological damage as indicated by a decrease in liver injury markers, LDH, hepatic MDA, and NOx levels, as well as increase anti-oxidative parameters. Besides, the anti-fibrotic efficacy of Vinpo was confirmed by decreasing hydroxyproline, and α-SMA. Also, the anti-inflammatory effect of Vinpo was explored by decreasing IL-6 and TNF-α levels. Our novel findings were that Vinpo decreased VEGF/Ki-67 expression in the liver confirming its effect on angiogenesis and proliferation. These findings reveal the anti-fibrotic effect of Vinpo against TAA-induced liver fibrosis in rats, and suggest the modulation of oxidative stress, inflammation, angiogenesis and proliferation as mechanistic cassette underlines this effect.

scholarly journals Comparative Study on Effect of Mesenchymal Stem Cells and Endothelial Progenitor Cells on Treatment of Experimental CCL4 Induced Liver Fibrosis

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
D Sabry ◽  
W A Khalifa ◽  
M M Abdelgwad ◽  
M Alhelf ◽  
Z M Altaib
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Treated Group ◽  
Ki 67

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) and human umbilical cord endothelial progenitor cells (UC-EPCs) have several benefits for liver regeneration. We speculate huge impacts of rat BM-MSCs and UC-EPCs on reversal of hepatic injury and improvement of liver function in liver fibrosis induced by carbon tetrachloride (CCl4). Methods Forty adult rats were divided into 4 groups; control group, CCl4 group, CCl4/BM-MSCs group and CCl4/UCEPCs group. Blood samples were driven from rats at 1, 2 and 3months to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of HGF,TGF-β, MMP-2, and VEGF were assessed by polymerase chain reaction. Histological examination of the liver tissue was performed. α-SMA immunohistochemistry to identify the myoepithelial cells (MECs) and Ki-67 to identify cell prolifration immunohistochemistry are detected in groups injected with cells to confirm cells regeneration. Results Regarding liver function, there was elevating albumin (P < 0.05) and reducing ALT (P < 0.05) concentrations in groups treated with BM-MSCs and UC-EPCs effect compared to untreated CCL4 group. Concerning gene expression, UC-EPCs treated group have significantly higher MMP-2 and VEGF (P < 0.01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BM-MSCs in increasing gene expression of HGF (P < 0.05) and immunohistochemistry of α-SMA and Ki-67 (P < 0.01). BM-MSCs have significantly lower TGF- β (P < 0.00) compared to UC-EPCs. Conclusion This study highlighted on liver regeneration role of both human UC-EPCs and BM-MSCs in liver fibrosis by different signaling mechanistic.

scholarly journals Cocoa Flavonoids Reduce Inflammation and Oxidative Stress in a Myocardial Ischemia-Reperfusion Experimental Model

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 167 ◽  
Author(s):  
Sajeela Ahmed ◽  
Naseer Ahmed ◽  
Alessio Rungatscher ◽  
Daniele Linardi ◽  
Bibi Kulsoom ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Sprague Dawley ◽  
Myocardial Apoptosis ◽  
Sprague Dawley Rats ◽  
Coronary Ischemia ◽  
Coronary Events ◽  
Myocardial Ischemia Reperfusion ◽  
Membrane Peroxidation

Consumption of flavonoid-rich nutraceuticals has been associated with a reduction in coronary events. The present study analyzed the effects of cocoa flavonols on myocardial injury following acute coronary ischemia-reperfusion (I/R). A commercially available cocoa extract was identified by chromatographic mass spectrometry. Nineteen different phenolic compounds were identified and 250 mg of flavan-3-ols (procyanidin) were isolated in 1 g of extract. Oral administration of cocoa extract in incremental doses from 5 mg/kg up to 25 mg/kg daily for 15 days in Sprague Dawley rats (n = 30) produced a corresponding increase of blood serum polyphenols and become constant after 15 mg/kg. Consequently, the selected dose (15 mg/kg) of cocoa extract was administered orally daily for 15 days in a treated group (n = 10) and an untreated group served as control (n = 10). Both groups underwent surgical occlusion of the left anterior descending coronary artery and reperfusion. Cocoa extract treatment significantly reversed membrane peroxidation, nitro-oxidative stress, and decreased inflammatory markers (IL-6 and NF-kB) caused by myocardial I/R injury and enhanced activation of both p-Akt and p-Erk1/2. Daily administration of cocoa extract in rats is protective against myocardial I/R injury and attenuate nitro-oxidative stress, inflammation, and mitigates myocardial apoptosis.

Undernutrition enhances alcohol-induced hepatocyte proliferation in the liver of rats fed via total enteral nutrition

2007 ◽  
Vol 293 (1) ◽  
pp. G355-G364 ◽  
Author(s):  
January N. Baumgardner ◽  
Kartik Shankar ◽  
Sohelia Korourian ◽  
Thomas M. Badger ◽  
Martin J. J. Ronis
Keyword(s):  
Oxidative Stress ◽  
Cellular Proliferation ◽  
Liver Steatosis ◽  
Hepatocyte Proliferation ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cyp 2E1 ◽  
Increased Risk ◽  
Etoh Group

To assess the relative contributions of undernutrition and ethanol (EtOH) exposure to alcohol-induced hepatotoxicity, female Sprague-Dawley rats were intragastrically infused liquid diets containing 187 or 154 kcal·kg−3/4·day−1 with or without 11 g·kg−1·day−1 EtOH. EtOH clearance was impaired in the 154 kcal·kg−3/4·day−1 EtOH group ( P ≤ 0.05). A combination of undernutrition and EtOH also increased the induction of hepatic cytochrome P-450 (CYP)2E1 and CYP4A1 mRNA, apoprotein, and activities ( P ≤ 0.05). This was accompanied by increased oxidative stress ( P ≤ 0.05). The severity of liver steatosis, macrophage infiltration, and focal necrosis was comparable in both EtOH groups. Alanine aminotransferase levels were elevated ( P ≤ 0.05) but did not significantly differ between the two EtOH groups. TUNEL analysis also demonstrated a comparable increase in apoptosis in the two EtOH groups ( P ≤ 0.05). The development of alcohol-induced liver pathology was accompanied by little change in fatty acid (FA) synthesis or degradation at 187 kcal·kg−3/4·day−1 but at 154 kcal·kg−3/4·day−1 was accompanied by decreased expression of FA synthesis genes and increased expression of peroxisome proliferator-activated receptor-α (PPAR-α)-regulated FA degradation pathways ( P ≤ 0.05). In addition, 154 kcal·kg−3/4·day−1 EtOH group livers exhibited greater hepatocyte proliferation ( P ≤ 0.05). We conclude that undernutrition does not exacerbate alcoholic steatohepatitis despite additional oxidative stress produced by an increased induction of CYP2E1 and CYP4A1. However, enhanced ethanol-induced cellular proliferation, perhaps as a result of enhanced PPAR-α signaling, may contribute to an increased risk of hepatocellular carcinoma in undernourished alcoholics.

Effects of probiotic bacteria on mucosal polyamines levels in dogs with IBD and colonic polyps: a preliminary study

2018 ◽  
Vol 9 (2) ◽  
pp. 247-255 ◽  
Author(s):  
G. Rossi ◽  
M. Cerquetella ◽  
S. Scarpona ◽  
G. Pengo ◽  
K. Fettucciari ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Caspase 3 ◽  
Cellular Proliferation ◽  
Activity Index ◽  
Clinical Activity ◽  
High Concentration ◽  
Ki 67 ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Spermine (SPM) and its precursor putrescine (PUT), regulated by ornithine decarboxylase (ODC) and diamino-oxidase (DAO), are polyamines required for cell growth and proliferation. Only a few studies have investigated the anti-inflammatory and tumour inhibitory properties of probiotics on mucosal polyamine levels. We investigated the effects of a high concentration multistrain probiotic for human use on colonic polyamine biosynthesis in dogs. Histological sections (inflammatory bowel disease, n=10; polyposis, n=5) were assessed after receiving 112 to 225×109 lyophilised bacteria daily for 60 days at baseline (T0) and 30 days after treatment end (T90). Histology scores, expression of PUT, SPM, ODC and DAO, and a clinical activity index (CIBDAI) were compared at T0 and T90. In polyps, cellular proliferation (Ki-67 expression), and apoptosis (caspase-3 protein expression) were also evaluated. After treatment, in inflammatory bowel disease significant decreases were observed for CIBDAI (P=0.006) and histology scores (P<0.001); PUT, SPM and ODC expression increased (P<0.01). In polyps, a significant decrease in polyamine levels, ODC activity, and Ki-67, and a significant increase in caspase-3 positivity and DAO expression (P=0.005) was noted. Our results suggest potential anti-proliferative and anti-inflammatory effects of the probiotic mixture in polyps and inflammation, associated with reduced mucosal infiltration and up-regulation of PUT, SPM, and ODC levels.

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

2021 ◽  
pp. 036354652110598
Author(s):  
Halil Sezgin Semis ◽  
Cihan Gur ◽  
Mustafa Ileriturk ◽  
Fatih Mehmet Kandemir ◽  
Ozgur Kaynar
Keyword(s):  
Oxidative Stress ◽  
Achilles Tendinopathy ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alternative Treatment Option ◽  
Markers Of Oxidative Stress ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The One

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

scholarly journals Maresin 1, a Proresolving Lipid Mediator, Ameliorates Liver Ischemia-Reperfusion Injury and Stimulates Hepatocyte Proliferation in Sprague-Dawley Rats

2020 ◽  
Vol 21 (2) ◽  
pp. 540 ◽  
Author(s):  
Gonzalo Soto ◽  
María José Rodríguez ◽  
Roberto Fuentealba ◽  
Adriana V. Treuer ◽  
Iván Castillo ◽  
...  
Keyword(s):  
Cell Division ◽  
Liver Injury ◽  
Mitotic Activity ◽  
Activity Index ◽  
Ischemia Reperfusion ◽  
Hepatocyte Proliferation ◽  
Liver Ischemia ◽  
Tnf Α ◽  
Mitotic Activity Index ◽  
Maresin 1

Maresin-1 (MaR1) is a specialized pro-resolving mediator, derived from omega-3 fatty acids, whose functions are to decrease the pro-inflammatory and oxidative mediators, and also to stimulate cell division. We investigated the hepatoprotective actions of MaR1 in a rat model of liver ischemia-reperfusion (IR) injury. MaR1 (4 ng/gr body weight) was administered prior to ischemia (1 h) and reperfusion (3 h), and controls received isovolumetric vehicle solution. To analyze liver function, transaminases levels and tissue architecture were assayed, and serum cytokines TNF-α, IL-6, and IL-10, mitotic activity index, and differential levels of NF-κB and Nrf-2 transcription factors, were analyzed. Transaminase, TNF-α levels, and cytoarchitecture were normalized with the administration of MaR1 and associated with changes in NF-κB. IL-6, mitotic activity index, and nuclear translocation of Nrf-2 increased in the MaR1-IR group, which would be associated with hepatoprotection and cell proliferation. Taken together, these results suggest that MaR1 alleviated IR liver injury, facilitated by the activation of hepatocyte cell division, increased IL-6 cytokine levels, and the nuclear localization of Nrf-2, with a decrease of NF-κB activity. All of them were related to an improvement of liver injury parameters. These results open the possibility of MaR1 as a potential therapeutic tool in IR and other hepatic pathologies.

scholarly journals Skimmin, a Coumarin fromHydrangea paniculata, Slows down the Progression of Membranous Glomerulonephritis by Anti-Inflammatory Effects and Inhibiting Immune Complex Deposition

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sen Zhang ◽  
Hongqi Xin ◽  
Yan Li ◽  
Dongming Zhang ◽  
Jing Shi ◽  
...  
Keyword(s):  
Rat Model ◽  
Interleukin 1 ◽  
Membranous Glomerulonephritis ◽  
Treated Group ◽  
Sprague Dawley ◽  
Tubulointerstitial Injury ◽  
Model Control ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Pharmacologically Active

Skimmin is one of the major pharmacologically active molecules present inHydrangea paniculata, a medical herb used in the traditional Chinese medicine as an anti-inflammatory agent. In the current study, we attempted to investigate its renoprotective activity and underlying mechanisms in a rat model of membranous glomerulonephritis induced by cationic bovine serum albumin (c-BSA). Sprague-Dawley (SD) rats were divided into five groups, including normal control, model control, Mycophenolate Mofetil-treated group, and two skimming-treated groups (15 mg/kg and 30 mg/kg). Our research showed that treatment with skimmin significantly reduced the levels of blood urea nitrogen (BUN), urinary albumin excretion (UAE), and serum creatinine (Scr) as compared with model control after experimental induction of membranous glomerulonephritis (P<0.01). Moreover, glomerular hypercellularity, tubulointerstitial injury, and glomerular deposition of IgG were less intense after skimmin treatment. By immunochemistry analysis, we demonstrated that skimmin could significantly inhibit interleukin-1β(IL1β) and IL-6 expression (P<0.05), reduce the loss of nephrin and podocin, and suppress the infiltration of renal interstitium by CD3-positive T cell and CD20-positive B cell. These results suggest that treatment with skimmin can significantly improve renal function and suppress the IgG deposition as well as the development of glomerular lesions in a rat model of membranous glomerulonephritis.

Astilbin Protects Against Carbon Tetrachloride-Induced Liver Fibrosis in Rats

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Xiao-Hui Sun ◽  
He Zhang ◽  
Xiao-Ping Fan ◽  
Zhao-Hui Wang
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Food Plants ◽  
Sprague Dawley ◽  
Glutamate Cysteine Ligase ◽  
Collagen Production ◽  
And Oxidative Stress

<b><i>Background:</i></b> Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. <b><i>Objectives:</i></b> This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. <b><i>Methods:</i></b> Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. <b><i>Results:</i></b> We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. <b><i>Conclusions:</i></b> Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.

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