Norbornene derived nanocarrier reduces isoniazid mediated liver toxicity: assessment in HepG2 cell line and zebrafish model

RSC Advances ◽  
2016 ◽  
Vol 6 (115) ◽  
pp. 114927-114936 ◽  
Author(s):  
Thangam Anju ◽  
Radhakrishnan Preetha ◽  
Raja Shunmugam ◽  
Shivshankar R. Mane ◽  
Jesu Arockiaraj ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Liver Toxicity ◽  
Toxicity Assessment ◽  
Hepg2 Cell Line ◽  
Stimuli Responsive ◽  
Zebrafish Model

The aim of this study was to investigate the protective effect of the stimuli-responsive norbornene-based nanocarrier complex of isoniazid, compared to pure isoniazid, on liver cells, by in vivo and in vitro methods.

scholarly journals Characterization of In Vitro 3D Cell Model Developed from Human Hepatocellular Carcinoma (HepG2) Cell Line

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2557
Author(s):  
Martina Štampar ◽  
Barbara Breznik ◽  
Metka Filipič ◽  
Bojana Žegura
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Cell Model ◽  
Human Hepatocellular Carcinoma ◽  
Time Dependent ◽  
Hepg2 Cell Line ◽  
Cell Models

In genetic toxicology, there is a trend against the increased use of in vivo models as highlighted by the 3R strategy, thus encouraging the development and implementation of alternative models. Two-dimensional (2D) hepatic cell models, which are generally used for studying the adverse effects of chemicals and consumer products, are prone to giving misleading results. On the other hand, newly developed hepatic three-dimensional (3D) cell models provide an attractive alternative, which, due to improved cell interactions and a higher level of liver-specific functions, including metabolic enzymes, reflect in vivo conditions more accurately. We developed an in vitro 3D cell model from the human hepatocellular carcinoma (HepG2) cell line. The spheroids were cultured under static conditions and characterised by monitoring their growth, morphology, and cell viability during the time of cultivation. A time-dependent suppression of cell division was observed. Cell cycle analysis showed time-dependent accumulation of cells in the G0/G1 phase. Moreover, time-dependent downregulation of proliferation markers was shown at the mRNA level. Genes encoding hepatic markers, metabolic phase I/II enzymes, were time-dependently deregulated compared to monolayers. New knowledge on the characteristics of the 3D cell model is of great importance for its further development and application in the safety assessment of chemicals, food products, and complex mixtures.

HGF ameliorates a high-fat diet-induced fatty liver

2007 ◽  
Vol 293 (1) ◽  
pp. G204-G210 ◽  
Author(s):  
Takashi Kosone ◽  
Hitoshi Takagi ◽  
Norio Horiguchi ◽  
Yasuyo Ariyama ◽  
Toshiyuki Otsuka ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fatty Liver ◽  
Cell Line ◽  
Hepg2 Cell ◽  
High Fat Diet ◽  
Normal Diet ◽  
Hepg2 Cell Line ◽  
High Fat

Hepatocyte growth factor (HGF) has various effects especially on epithelial cells. However, the precise role of HGF on lipogenesis is still not fully understood. A high-fat diet was administered to HGF transgenic mice and wild-type control mice in vivo. Furthermore, recombinant human HGF (rhHGF) was administered to HepG2 cell line in vitro. We performed an analysis regarding the factors relating to lipid metabolism. An overexpression of HGF dramatically ameliorates a high-fat diet-induced fatty liver. HGF transgenic mice showed an apparently reduced lipid accumulation in the liver. The activation of microsomal triglyceride transfer protein (MTP) and apolipoprotein B (ApoB) accompanying higher triglyceride levels in the serum were found in HGF transgenic mice on a normal diet. Interestingly, this upregulation of the MTP activation became more apparent in the high-fat diet. In addition, the administration of rhHGF stimulated MTP and ApoB expression while reducing reduced the intracellular lipid content in HepG2 cell line. However, this induction of MTP and ApoB by HGF was clearly inhibited by PD98059 (MAPK inhibitor). In conclusion, the data presented in this study indicated that HGF ameliorates a high-fat diet-induced fatty liver via the activation of MTP and ApoB.

Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma

2016 ◽  
Vol 397 (3) ◽  
pp. 257-267 ◽  
Author(s):  
Mohammed M.H. Al-Gayyar ◽  
Ahmed Abbas ◽  
Ahmed M. Hamdan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Extracellular Enzyme ◽  
Dependent Manner ◽  
Hepg2 Cell Line ◽  
Tnf Α ◽  
Dose Dependent

Abstract Sulfatase 2 (SULF2) is an extracellular enzyme that catalyzes the removal of 6-O-sulfate groups from the heparan sulfate (HS). As elevated SULF2 activity has been correlated with hepatocellular carcinoma (HCC), this study was conducted to evaluate the chemoprotective and the hepatoprotective roles of adiponectin, as a SULF2 inhibitor, against hepatocellular carcinoma both in vivo and in vitro. HCC was induced in rats using thioacetamide (200 mg/kg). Treated rats received adiponectin (5 μg/kg) once a week. Moreover, human hepatocellular carcinoma (HepG2) cell line was used as an in-vitro model. In both in-vivo and in-vitro models, adiponectin completely blocked HCC-induced SULF2 elevation. The antitumor activity of adiponectin was confirmed by 80% increased the survival rate, 73% reduction in the average number of nodules per nodule-bearing liver and 46% reduction in serum AFP. In addition, adiponectin ameliorated HCC-induced expression of tumor invasion markers, MMP9, syndecan-1 and FGF-2. Moreover, adiponectin attenuated HCC-induced elevation of nfκb and TNF-α levels. Moreover, treatment of HepG2 cell line with adiponectin showed dose-dependent reduction of HepG2 cell viability and elevation of cellular cytotoxicity. Besides, Adiponectin yielded the same results in HepG2 cells in a dose-dependent manner. Adiponectin achieved both hepatoprotective and chemoprotective effects against HCC through blocking of SULF2.

scholarly journals Synthesis and Antiplasmodial Evaluation of 4-Carboxamido- and 4-Alkoxy-2-Trichloromethyl Quinazolines

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3929
Author(s):  
Dyhia Amrane ◽  
Armand Gellis ◽  
Sébastien Hutter ◽  
Marion Prieri ◽  
Pierre Verhaeghe ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Alkoxy Group ◽  
Hepg2 Cell Line ◽  
Ccl3 Group ◽  
Falciparum Strain ◽  
Structure Activity ◽  
Trichloromethyl Group ◽  
Sar Study

From three previously identified antiplasmodial hit compounds (A–C) and inactive series (D), all based on a 2-trichloromethylquinazoline scaffold, we conducted a structure-activity relationship (SAR) study at position four of the quinazoline ring by synthesizing 42 novel derivatives bearing either a carboxamido- or an alkoxy-group, to identify antiplasmodial compounds and to enrich the knowledge about the 2-trichloromethylquinazoline antiplasmodial pharmacophore. All compounds were evaluated in vitro for their cytotoxicity towards the HepG2 cell line and their activity against the multiresistant K1 P. falciparum strain, using doxorubicin, chloroquine and doxycycline as reference drugs. Four hit-compounds (EC50 K1 P. falciparum ≤ 2 µM and SI ≥ 20) were identified among 4-carboxamido derivatives (2, 9, 16, and 24) and two among 4-alkoxy derivatives (41 and 44). Regarding the two most potent molecules (16 and 41), five derivatives without a 2-CCl3 group were prepared, evaluated, and appeared totally inactive (EC50 > 50 µM), showing that the 2-trichloromethyl group was mandatory for the antiplasmodial activity.

Evaluation of in vitro antioxidant activities of soyasaponins from soy hypocotyls in human HepG2 cell line

2016 ◽  
Vol 71 (3) ◽  
pp. 653-660 ◽  
Author(s):  
Lijie Zhu ◽  
Minghan Zhang ◽  
Xiuying Liu ◽  
He Liu ◽  
Yutang He ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Antioxidant Activities ◽  
Hepg2 Cell Line

Looking for synergy or additivity between 188Re and sorafenib on hepatoma cell lines.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 247-247
Author(s):  
Marc Pracht ◽  
Nicolas Lepareur ◽  
Julien Edeline ◽  
Laurence Lenoir ◽  
Valerie Ardisson ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
External Beam Radiotherapy ◽  
Combined Treatment ◽  
Hepatoma Cell Lines ◽  
Heparg Cell Line

247 Background: In case of non resectable HCC, radioembolization and sorafenib (S) are therapeutic options respectively for intermediate and advanced stages. In some other cancers, there is an increase of efficacy when external beam radiotherapy is done concomitantly with systemic chemotherapy or targeted therapies. So we wondered if there could be a synergistic or an additive activity when S is combined with a radionuclide. Methods: Hepatoma cell lines N1S1 (murine HCC), HepG2 (human hepatoblastoma) and HepaRG (human HCC) were treated with increasing concentrations of rhenium-188 (188Re) or S. On each cell line, we have studied the cellular toxicities of S and 188Re using Tetrazolium dye test, extra-cellular medium LDH level and morphologic analysis. This was done for different dosage of S and 188Re. We measured the lethal concentration killing 25% of cells (LC25) with the results of the Tetrazolium dye test. Secondly, we looked for synergy or additivity on cellular toxicity of these two compounds according to cell lines by combined treatment. Synergy or additivity was estimated with the combination index (CI) method (synergy if CI lower than 1, additivity if CI = 1, antagonism if CI upper to 1) based on the Tetrazolium dye test’s results. Results: Monotherapy dose-dependent toxicities were observed for all three cell lines with 188Re and for the N1S1 and HepG2 cell lines only with S. Combined treatment with 188Re and S showed synergy on HepaRG and N1S1 cell lines and additivity on the HepG2 cell line. Conclusions: The additive, and even synergistic, interest of a combined treatment with 188Re and S is demonstrated in vitro (for the first time to our knowledge) on hepatoma cell lines. This results, in particular for the HepaRG cell line (human HCC), could be explained by the down-regulation of the hepatic drug transporters which are responsible for the Sorafenib efflux in case of simultaneous DNA damages due to a radionuclide exposition. This promising approach now needs to be confirmed in vivo. [Table: see text]

scholarly journals Evaluation of Antioxidant and Antidiabetic Potential of Polyherbal Drug Made with Three Herbs: An In vitro Cell Culture Model

2021 ◽  
Vol 14 (4) ◽  
pp. 1627-1635
Author(s):  
P. Chandrasekaran
Keyword(s):  
Cell Culture ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Plant Extracts ◽  
Antioxidant Properties ◽  
Protein Glycation ◽  
Gas Chromatography Mass Spectrometry ◽  
Individual Plant ◽  
Hepg2 Cell Line

In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial “hyperglycemic spikes” may be relevant to the onset of cardiovascular complications has recently received much attention. Medicinal use of herbal medicine in the treatment and prevention of diseases including diabetes has a long history compared to conventional medicine. These plants have no side effects and many existing medicines are derived from the plants. Hence, the current investigation was planned to make a poly herbal drug (PHD) through Punica granatum (fruits), Illicium verum (flowers) and Nyctanthes arbor (leaves) and assess their antioxidant and antidiabetic activities in vitro and in HepG2 cell line. The respective plant methanolic extracts and PHD are exposed to phytochemical assessment and to discriminate the bioactive factors by Gas Chromatography–Mass Spectrometry. We evaluated the antioxidant properties 2, 2-diphenyl-1-picrylhydrazyl scavenging, hydrogen peroxide scavenging, thiobarbituric acid reactive substances and total antioxidant activity of individual plant extracts and the PHD. At the same time, In vitro and cell culture approaches were used to assess the anti-diabetic activity. The PHD has a higher concentration of secondary metabolites than individual plant extracts, according to our findings. On the other hand, we also notice that PHD demonstrated higher antioxidant capability and considerable in vitro glucose-lowering effects along with noteworthy inhibition of ɑ-amylase, glucosidase, lipase, dipeptidyl peptidase-IV, collagenase and protein glycation in HepG2 cell line. In conclusion, this study clearly demonstrated the significant antioxidant and antidiabetic activities of the PHD. Hence, PHD may be used as a potential source in the management of diabetes, hyperglycemia and the related state of oxidative stress.

Synthesis, Characterization and Anti-hepatoma Activity of New Hederagenin Derivatives

2020 ◽  
Vol 20 (3) ◽  
pp. 252-257
Author(s):  
Xiao Liu ◽  
Lu Sun ◽  
Qing-Hua Liu ◽  
Bao-Quan Chen ◽  
Yu-Ming Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Normal Cell ◽  
Biological Significance ◽  
Cancer Cell Line ◽  
Human Hepatocellular Carcinoma ◽  
Hepg2 Cell Line ◽  
Normal Cell Line

Background: Based on the biological significance of hederagenin-type saponins found in our previous investigation, a series of new hederagenin derivatives were designed and synthesized. Methods : Their in vitro antiproliferative activities were evaluated against the HepG2 liver cancer cell line and normal cell line L929 by MTT assay. Results: The preliminary bioassay results demonstrated that all the tested compounds 1-7 showed potent anti-hepatoma activities, and some compounds exhibited better effects than 5-fluorouracil against human hepatocellular carcinoma HepG2 cell line. Furthermore, compound 5 showed a significant antihepatoma activity against HepG2 cells with an IC50 value of 1.88 µM. Besides, all of the tested compounds showed a low cytotoxic effect against the normal cell line L929. Conclusion: All the compounds 1-7 displayed superior selectivity against human hepatocellular carcinoma HepG2 cell line, and the results suggest that the structural modifications of C ring on the hederagenin backbone are vital for modulating anti-hepatoma activities.

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