scholarly journals Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 195
Author(s):  
Quaiser Saquib ◽  
Abdullah M. Al-Salem ◽  
Maqsood A. Siddiqui ◽  
Sabiha M. Ansari ◽  
Xiaowei Zhang ◽  
...  
Keyword(s):  
Flame Retardant ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Human Cancer ◽  
Liver Cells ◽  
Consumer Products ◽  
In Vivo Test ◽  
Human Liver Cells

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

scholarly journals Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Irit Meivar-Levy ◽  
Tamar Sapir ◽  
Dana Berneman ◽  
Tal Weissbach ◽  
Sylvie Polak-Charcon ◽  
...  
Keyword(s):  
Human Liver ◽  
Developmental Plasticity ◽  
Liver Cells ◽  
Lineage Tracing ◽  
Hepatic Tissue ◽  
Diabetic Patients ◽  
Human Liver Cells ◽  
Insulin Producing Cells

Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species bothin vivoandin vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using anin vitroexperimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.

The effect of liver donors’ age, gender and metabolic state on pancreatic lineage activation

2021 ◽  
Vol 16 (1) ◽  
pp. 19-31
Author(s):  
Ioan V Matei ◽  
Irit Meivar-Levy ◽  
Daniela Lixandru ◽  
Simona Dima ◽  
Ioana R Florea ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Human Liver ◽  
Liver Cells ◽  
Diabetic Patients ◽  
Metabolic State ◽  
Human Liver Cells ◽  
Metabolic States ◽  
Different Ages ◽  
Liver Donors

Autologous cells replacement therapy by liver to pancreas transdifferentiation (TD) allows diabetic patients to be also the donors of their own therapeutic tissue. Aim: To analyze whether the efficiency of the process is affected by liver donors’ heterogeneity with regard to age, gender and the metabolic state. Materials & methods: TD of liver cells derived from nondiabetic and diabetic donors at different ages was characterized at molecular and cellular levels, in vitro. Results: Neither liver cells proliferation nor the propagated cells TD efficiency directly correlate with the age (3–60 years), gender or the metabolic state of the donors. Conclusion: Human liver cells derived from a wide array of ages and metabolic states can be used for autologous cells therapies for diabetics.

Protective effects of papaya extracts on tert-butyl hydroperoxide mediated oxidative injury to human liver cells (An in-vitro study)

2012 ◽  
Vol 2 (3) ◽  
pp. 10-19 ◽  
Author(s):  
Sheri-Ann Tan ◽  
Sonia Ramos ◽  
María Angeles Martin ◽  
Raquel Mateos ◽  
Michael Harvey ◽  
...  
Keyword(s):  
Human Liver ◽  
In Vitro Study ◽  
Oxidative Injury ◽  
Liver Cells ◽  
Vitro Study ◽  
Protective Effects ◽  
Butyl Hydroperoxide ◽  
Human Liver Cells ◽  
Tert Butyl Hydroperoxide

scholarly journals Codon Optimization of Gene Editing CRISPR‐SaCas9 Plasmid Increases Protein Expression in Human Liver Cells to Boost in vivo Therapeutic Knockout Application Efficiency

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Irene R. Madejski ◽  
Avirath Sundaresan ◽  
Tyler L. Groshong ◽  
Grace D. Holmes ◽  
Ishir G. Gupta ◽  
...  
Keyword(s):  
Protein Expression ◽  
Human Liver ◽  
Gene Editing ◽  
Codon Optimization ◽  
Liver Cells ◽  
Human Liver Cells ◽  
Application Efficiency

scholarly journals Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

2020 ◽  
Author(s):  
Yu Na Lee ◽  
Hye-Jin Yi ◽  
Eun Hye Seo ◽  
Jooyun Oh ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Human Liver ◽  
Cell Sheet ◽  
Liver Cells ◽  
Cell Sheets ◽  
Human Liver Cells ◽  
Insulin Producing Cells ◽  
Differentiation Efficiency

Abstract Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheets formation could improve differentiation efficiency and graft survival.Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. One and two weeks following IPC sheet transplantation, immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

Cytotoxicity evaluation of the alkaloid govaniadinein human liver cells and in vitro glucuronidation by liver microsomes

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
LMM Marques ◽  
U Rottkord ◽  
I Krug ◽  
M Behrens ◽  
A Adhikari ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Liver Cells ◽  
Human Liver Cells

scholarly journals Comparing in vitro human liver models to in vivo human liver using RNA-Seq

2020 ◽  
Author(s):  
Rajinder Gupta ◽  
Yannick Schrooders ◽  
Duncan Hauser ◽  
Marcel van Herwijnen ◽  
Wiebke Albrecht ◽  
...  
Keyword(s):  
Liver Cell ◽  
Liver Tissue ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Rna Seq ◽  
Cell Models ◽  
Human Liver Tissue ◽  
Human Liver Cell

Abstract The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues. First, using CellNet, we analyzed whether these liver in vitro cell models were indeed classified as liver, based on their baseline expression profile and gene regulatory networks (GRN). More comprehensive analyses using non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) were applied to assess the coverage for important liver pathways. Through different analyses, we noticed that 3D liver microtissues exhibited a high similarity with in vivo liver, in terms of CellNet (C/T score: 0.98), non-DEGs (10,363) and pathway coverage (highest for 19 out of 20 liver specific pathways shown) at the beginning of the incubation period (0 h) followed by a decrease during long-term incubation for 168 and 336 h. PHH also showed a high degree of similarity with human liver tissue and allowed stable conditions for a short-term cultivation period of 24 h. Using the same metrics, HepG2 cells illustrated the lowest similarity (C/T: 0.51, non-DEGs: 5623, and pathways coverage: least for 7 out of 20) with human liver tissue. The HepG2 are widely used in hepatotoxicity studies, however, due to their lower similarity, they should be used with caution. HepaRG models, iPSC-HLCs, and hPCLiS ranged clearly behind microtissues and PHH but showed higher similarity to human liver tissue than HepG2 cells. In conclusion, this study offers a resource of RNA-Seq data of several biological replicates of human liver cell models in vitro compared to human liver tissue.

scholarly journals In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites

2015 ◽  
Vol 4 (5) ◽  
pp. 1289-1296 ◽  
Author(s):  
S. Meyer ◽  
G. Raber ◽  
F. Ebert ◽  
L. Leffers ◽  
S. M. Müller ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Human Liver ◽  
Liver Cells ◽  
Human Liver Cells ◽  
Cells In Culture

Arsenic-containing fatty acids are bioavailable and toxic to human liver cells in culture.

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