scholarly journals Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells

2013 ◽  
Vol 64 (2) ◽  
pp. 189-200 ◽  
Author(s):  
Anja Fic ◽  
Bojana Žegura ◽  
Marija Sollner Dolenc ◽  
Metka Filipič ◽  
Lucija Peterlin Mašič
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Bisphenol A ◽  
Hepatoma Cell ◽  
Metabolic Activation ◽  
Living Environment ◽  
Male Rat ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Structural Analogues

Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production and use are increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic and genotoxic potential of eight BPA structural analogues (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, and BP-2) using the Ames and comet assay, respectively. None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver). Potential genotoxicity of bisphenols was determined in the human hepatoma cell line (HepG2) at non-cytotoxic concentrations (0.1 μmol L-1 to 10 μmol L-1) after 4-hour and 24-hour exposure. In the comet assay, BPA and its analogue BPS induced significant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks

scholarly journals Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 3821
Author(s):  
Anne-Margarethe Enge ◽  
Florian Kaltner ◽  
Christoph Gottschalk ◽  
Albert Braeuning ◽  
Stefanie Hessel-Pras
Keyword(s):  
Pyrrolizidine Alkaloids ◽  
Hepatoma Cell ◽  
Metabolic Activation ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Food Contaminants ◽  
Plant Metabolites ◽  
Human Hepatoma Cell ◽  
Secondary Plant Metabolites ◽  
Heparg Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.

Metabolic activation of benzo[a]pyrene by a human hepatoma cell line

1980 ◽  
Vol 1 (10) ◽  
pp. 871-875 ◽  
Author(s):  
Leila Diamond ◽  
Francis Kruszewski ◽  
David P. Aden ◽  
Barbara B. Knowles ◽  
William M. Baird
Keyword(s):  
Cell Line ◽  
Hepatoma Cell ◽  
Metabolic Activation ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Human Hepatoma Cell Line

scholarly journals Stimulation of de novo glutathione synthesis by nitrofurantoin for enhanced resilience of hepatocytes

2021 ◽  
Author(s):  
Lukas S. Wijaya ◽  
Carina Rau ◽  
Theresa S. Braun ◽  
Serif Marangoz ◽  
Vincent Spegg ◽  
...  
Keyword(s):  
De Novo ◽  
Hepatoma Cell ◽  
Proteasome Inhibitors ◽  
Essential Element ◽  
Hepatoma Cell Line ◽  
Related Factor ◽  
Human Hepatoma Cell ◽  
Intact Cells ◽  
Intracellular Glutathione ◽  
Endogenous Antioxidant

AbstractToxicity is not only a function of damage mechanisms, but is also determined by cellular resilience factors. Glutathione has been reported as essential element to counteract negative influences. The present work hence pursued the question how intracellular glutathione can be elevated transiently to render cells more resistant toward harmful conditions. The antibiotic nitrofurantoin (NFT) was identified to stimulate de novo synthesis of glutathione in the human hepatoma cell line, HepG2, and in primary human hepatocytes. In intact cells, activation of NFT yielded a radical anion, which subsequently initiated nuclear-factor-erythroid 2-related-factor-2 (Nrf2)-dependent induction of glutamate cysteine ligase (GCL). Application of siRNA-based intervention approaches confirmed the involvement of the Nrf2-GCL axis in the observed elevation of intracellular glutathione levels. Quantitative activation of Nrf2 by NFT, and the subsequent rise in glutathione, were similar as observed with the potent experimental Nrf2 activator diethyl maleate. The elevation of glutathione levels, observed even 48 h after withdrawal of NFT, rendered cells resistant to different stressors such as the mitochondrial inhibitor rotenone, the redox cycler paraquat, the proteasome inhibitors MG-132 or bortezomib, or high concentrations of NFT. Repurpose of the antibiotic NFT as activator of Nrf2 could thus be a promising strategy for a transient and targeted activation of the endogenous antioxidant machinery.

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