scholarly journals Potential Antifibrotic and Angiostatic Impact of Idebenone, Carnosine and Vitamin E in Nano-Sized Titanium Dioxide-Induced Liver Injury

2015 ◽  
Vol 35 (6) ◽  
pp. 2402-2411 ◽  
Author(s):  
Samy A. Abdelazim ◽  
Hebatallah A. Darwish ◽  
Sanaa A. Ali ◽  
Maha Z. Rizk ◽  
Mai O. Kadry
Keyword(s):  
Titanium Dioxide ◽  
Vitamin E ◽  
Growth Factor ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Hepatic Cell ◽  
Hepatic Tissue ◽  
Combination Regimen ◽  
Hepatic Cell Lines

Background/Aim: The present study investigated the in vitro and in vivo effects of individual and combined doses of idebenone, carnosine and vitamin E on ameliorating some of the biochemical indices of nano-sized titanium dioxide (n-TiO2) in mice liver. Methods: The in vitro cytotoxic effect of nano-sized anatase TiO2 (21 nm) on hepatic cell lines (HepG 2) was investigated. Additionally, n-TiO2 was orally administered (150 mg/kg/day) for 2 weeks, followed by a daily intragastric gavage of the aforementioned antioxidants for 1 month. Results: n-TiO2 induced significant cytotoxicity in hepatic cell lines and elevated the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic total antioxidant capacity (TAC) and nitrite/nitrate (NOx) levels. Meanwhile, glutathione-S-transferase (GST) activity was significantly reduced. Moreover, RT-PCR and western blot analysis showed that n-TiO2 significantly altered the mRNA and protein expressions of transforming growth factor-beta (TGF-β1) and Smad-2, as well as vascular endothelium growth factor (VEGF). Histopathological examination of hepatic tissue reinforced these results.Conclusion: Idebenone, carnosine and vitamin E ameliorated the deviated parameters with the combination regimen demonstrating the most pronounced effect. Oxidative stress, liver fibrosis and angiogenesis may be implicated in n-TiO2-induced liver toxicity.

Cellular crosstalk mediated by platelet-derived growth factor BB and transforming growth factor β during hepatic injury activates hepatic stellate cells

2018 ◽  
Vol 96 (8) ◽  
pp. 728-741 ◽  
Author(s):  
Sowmya Mekala ◽  
SubbaRao V. Tulimilli ◽  
Ramasatyaveni Geesala ◽  
Kanakaraju Manupati ◽  
Neha R. Dhoke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Platelet Derived Growth Factor ◽  
Hepatic Tissue

Apoptotic hepatocytes release factors that activate hepatic stellate cells (HSCs), thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride, or thioacetamide. Histology of hepatotoxicant-induced diseased hepatic tissue correlated with differential expression of fibrosis-related genes. A marked increase in co-staining of transforming growth factor β receptor type II (TGFRIIβ) – desmin or α-smooth muscle actin – platelet-derived growth factor receptor β (PDGFRβ), markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V – cytokeratin expressing hepatocytes. To understand the molecular mechanisms of disease pathology, in vitro experiments were designed using the conditioned medium (CM) of hepatotoxicant-treated HepG2 cells supplemented to HSCs. A significant increase in HSC proliferation, migration, and expression of fibrosis-related genes and protein was observed, thereby suggesting the characteristics of an activated phenotype. Treating HepG2 cells with hepatotoxicants resulted in a significant increase in mRNA expression of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ). CM supplemented to HSCs resulted in increased phosphorylation of PDGFRβ and TGFRIIβ along with its downstream effectors, extracellular signal-related kinase 1/2 and focal adhesion kinase. Neutralizing antibodies against PDGF-BB and TGFβ effectively perturbed the hepatotoxicant-treated HepG2 cell CM-induced activation of HSCs. This study suggests PDGF-BB and TGFβ as potential molecular targets for developing anti-fibrotic therapeutics.

Dioscorea villosa Leaf Extract Enhances in vitro Wound Healing and Expression of Extra Cellular Matrix Factors Transforming Growth Factor-Beta 1 and Collagen-1 in L929 Cell Lines

2019 ◽  
Vol 15 (66) ◽  
pp. 483
Author(s):  
SurapaneniKrishna Mohan ◽  
Murad Alsawalha ◽  
AbeerMohammed Al-Subaie ◽  
ReemYousuf Al-Jindan ◽  
SrinivasaRao Bolla ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Leaf Extract ◽  
Transforming Growth Factor ◽  
L929 Cell ◽  
Growth Factor Beta ◽  
Matrix Factors

Hepcidin Inhibition by Modified Heparins without Anticoagulant Activity

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 483-483
Author(s):  
Maura Poli ◽  
Domenico Girelli ◽  
Annamaria Naggi ◽  
Natascia Campostrini ◽  
Dario Finazzi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Conflicts Of Interest ◽  
Anticoagulant Activity ◽  
Hepatic Cell ◽  
Maximum Effect ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Hepatic Cell Lines

Abstract Abstract 483 Background. There is an increasing interest in the development of pharmacological agents able to modulate hepcidin, the peptide hormone that critically regulates iron metabolism. In particular, hepcidin antagonist may have a therapeutic role in the anemia of chronic diseases, where hepcidin levels are often increased by pro-inflammatory cytokines. We previously demonstrated that heparin is a potent inhibitor of hepcidin expression in hepatic cell lines, probably by interfering with BMP/HJV/SMAD signalling, and that it was also effective in reducing hepcidin expression in mice (Poli M, Blood 2011; 117:997–1004). Since the therapeutic use of heparin for hepcidin modulation is hampered by its strong anticoagulant activity, we were interested in evaluating modified heparins without such activity. Methods. Heparins modified to inactivate the antithrombin binding site, with different molecular weight and degree of sulfation, were supplied to hepatic cell lines and mice to evaluate their potential modulation of hepcidin expression. We analysed their interference with the BMP/SMAD signalling, as well as serum hepcidin levels in mice by mass spectrometry. Results. Over 20 modified heparins were initially screened by evaluating their dose-dependent suppression of hepcidin expression before and after BMP induction. All of them showed a certain degree of anti-hepcidin activity, with two glycol-split molecules being as potent as classical unfractionated heparin. These two molecules suppressed BMP/SMAD signalling in HepG2 cells at pharmacological concentrations with maximum inhibition after 6 hours. In mice, treatments with 20 or 60 mg/Kg did not affect coagulation but strongly reduced liver pSMAD, hepcidin mRNA and serum hepcidin. Again, the maximum effect on liver hepcidin expression was observed 6 hours after the injection. This effect was observed also in conditions of high hepcidin caused by experimental inflammation or iron overload. Conclusions. Some non-anticoagulant heparins have strong anti-hepcidin activity both in vitro and in vivo, and may represent promising hepcidin antagonist with potential therapeutic applications. Disclosures: No relevant conflicts of interest to declare.

Human placental trophoblast as an in vitro model for tumor progression

2002 ◽  
Vol 80 (2) ◽  
pp. 142-149 ◽  
Author(s):  
P K Lala ◽  
B P Lee ◽  
G Xu ◽  
C Chakraborty
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Negative Regulator ◽  
Extravillous Trophoblast ◽  
Epithelial Tumor ◽  
Genetic Changes

The human placenta is a highly invasive tumor-like structure in which a subpopulation of placental trophoblast cells known as the "extravillous trophoblast" (EVT) invades the uterine decidua and its vasculature to establish adequate fetal–maternal exchange of molecules. By utilizing in vitro-propagated short-lived EVT cell lines we found that molecular mechanisms responsible for their invasiveness are identical to those of cancer cells; however, unlike cancer cells, their proliferation, migration, and invasiveness in situ are stringently controlled by decidua-derived transforming growth factor (TGF)-β. By SV40T antigen transfection of normal EVT cells followed by a forced crisis regimen in culture we produced an immortalized premalignant derivative that is hyperproliferative, hyperinvasive, and deficient in gap-junctional intercellular communication. Both premalignant and malignant EVT (JAR and JEG-3 choriocarcinoma) cell lines were found to be TGF-β-resistant. Using these cell lines, we investigated genetic changes responsible for transition of the normal EVT cells to premalignant and malignant phenotype. Hyperinvasiveness in both cases resulted from a downregulation of tissue inhibitor of metalloprotease (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 genes. In contrast to normal EVT cells, both cell types failed to upregulate these genes in response to TGF-β. Loss of TGF-β response in malignant EVT cells was explained by the loss of expression of Smad3 gene. Differential mRNA display of normal and premalignant EVT cells identified up- and down-regulation of numerous known or novel genes in premalignant EVT cells, with potential oncogenic and (or) tumor-suppressor functions, e.g., loss of fibronectin and insulin-like growth factor binding protein (IGFBP-5). Premalignant EVT cells also lost IGF receptor type 2 (IGFR-II). IGFBP-5 was shown to be a negative regulator of IGF-1-induced proliferation of premalignant EVT cells, so that loss of IGFBP-5 as well as IGFR-II permitted their unrestricted proliferation in an IGF-I-rich microenvironment of the fetal–maternal interface. The present model may be a good prototype for identifying genetic changes underlying epithelial tumor progression.Key words: trophoblast, TGF-β, IGFBP-5, fibronectin, choriocarcinoma.

Impact of counterions on the toxicity of metallic nanoparticles on hepatic cell lines in vitro

2017 ◽  
Vol 280 ◽  
pp. S216
Author(s):  
Albert Braeuning ◽  
Holger Sieg ◽  
Linda Böhmert ◽  
Dajana Lichtenstein ◽  
Alfonso Lampen
Keyword(s):  
Cell Lines ◽  
Metallic Nanoparticles ◽  
Hepatic Cell ◽  
Hepatic Cell Lines

Evaluation of the Cytotoxic Effects of MEIC Chemicals 31–50 on Primary Culture of Rat Hepatocytes and Hepatic and Non-hepatic Cell Lines

1997 ◽  
Vol 25 (4) ◽  
pp. 423-436
Author(s):  
Xavier Ponsoda ◽  
Cristina Núñez ◽  
José Vicente Castell ◽  
Maria José Gómez-Lechón
Keyword(s):  
Primary Culture ◽  
Cell Lines ◽  
Rat Hepatocytes ◽  
In Vitro Cytotoxicity ◽  
Hepatic Cell ◽  
Cellular Systems ◽  
Human Toxicity ◽  
Response Curves ◽  
Hepatic Cell Lines

The cytotoxicities of 20 chemicals (numbers 31–50) from the Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme were assessed with a primary culture of rat hepatocytes and with two hepatic cell lines (Hep G2 and FaO) and one non-hepatic cell line (3T3). The cytotoxicities of the chemicals were evaluated by using the MTT test after the cells had been exposed to the chemicals for 24 hours. For a better evaluation of results, dose–response curves were mathematically linearised and cytotoxicity was expressed as IC50 values and IC10 values (the concentration causing 50% and 10% loss of cell viability, respectively). We found that all the compounds showed similar acute basal cytotoxicity in all four cellular systems (regardless of whether the cells were, or were not, metabolically competent or were or were not of human origin). When these results were used to predicit human toxicity in terms of a mathematical parameter (prediction error [PE]), we found that all four systems gave similar predictions of human toxicity. The best cytotoxicity parameter included in the PE calculation was the IC50/10, because of an underestimation of human toxicity by in vitro systems. However, when PEs were calculated for rodent toxicity, better results were obtained. Data from the literature obtained by using other experimental models for predicting human toxicity were analysed according to the same criteria. We conclude that cellular systems are better predictive tools for human toxicity than are prokaryotic cells or whole-organism models.

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