Hexafluoropropylene oxide dimer acid (GenX) exposure induces apoptosis in HepG2 cells

Yoo, Hee Joon; Pyo, Min Cheol; Park, Yoonjin; Kim, Bo Yong; Lee, Kwang Won

doi:10.1016/j.heliyon.2021.e08272

Cited by 14 publications

(3 citation statements)

References 53 publications

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“…In addition, we also further determined the mechanism of liver injury by observing the occurrence of ROS and apoptosis. In previously published literature, treatment of (40, 100, 250, and 500 μM) HepG2 cells with GenX for 12 h resulted in decreased cell viability, increased intracellular ROS production, induced oxidative stress in a dose-dependent manner, and caused apoptosis mediated by ROS . This may be due to the fact that the toxic effects of GenX on HepG2 are not the same at different treatment times, as evidenced by the changes in TC at 24 and 48 h in this study.…”

Section: Discussionmentioning

confidence: 99%

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

Shi,

Zhang,

et al. 2023

Chem. Res. Toxicol.

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Hexafluoropropylene oxide dimer acid (HFPO−DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 μg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 μM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1β, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

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Section: Discussionmentioning

confidence: 99%

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

Shi,

Zhang,

et al. 2023

Chem. Res. Toxicol.

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“…Our findings are in line with studies involving both human cells in vitro and plant species. Such studies have concluded that exposure to GenX induces an intracellular toxicity mechanism that leads to apoptosis and a reduction of cell viability (Yoo et al 2021 ). Similarly, GenX uptake has been observed to have an adverse effect on lettuce even at low concentration levels (100 μg L −1 ), which suggests that GenX could induce oxidative stress in lettuce plants (Wang et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

GenX uptake by wheat and rice in flooded and non-flooded soils: a greenhouse experiment

Al Zbedy,

Müller,

Kindness

et al. 2023

Environ Sci Pollut Res

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GenX (hexafluoropropylene oxide dimer acid) belongs to the group of per- and poly-fluoroalkyl substance (PFAS) compounds introduced to replace perfluorooctanoic acid (PFOA), which has been phased out in industrial and consumer product formulations. While GenX has been investigated in lab animals, there is limited information available regarding its uptake and translocation in wheat and rice. This study reports on a greenhouse experiment in which wheat and rice grown under flooded and non-flooded conditions were exposed to two GenX concentrations in the soil (0.4 mg kg−1 and 2 mg kg−1). GenX was analysed in the soil, porewater and shoots using targeted liquid chromatography-tandem mass spectroscopy (LC-MS/MS) analysis. Extractable organic fluorine (EOF) was determined using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-GFMAS) instrument. Results showed that different species took up different amounts of GenX. The GenX concentration in rice shoots was found to be 2.34 (± 0.45) and 4.11 (± 0.87) μg g−1 under flooded and non-flooded conditions, respectively, at a low exposure level. At high exposure, the GenX concentrations in flooded and non-flooded rice shoots increased threefold to 10.4 (± 0.41) and 13.4 (± 0.72) μg g−1, respectively. Wheat shoots showed similar concentrations and increases between low- and high-level exposure. The translocation factor was significantly higher (P = 0.013) in non-flooded rice compared to flooded rice. The GenX bioaccumulation behaviours under the same culture conditions (e.g. temperature, humidity, light, same GenX concentration in the soil) were significantly different in non-flooded and flooded rice (P < 0.001). Non-flooded rice plants displayed a higher level of GenX bioaccumulation than flooded ones. Following exposure to GenX, flooded rice plants showed a reduction in biomass (25%) compared to the control plants (P < 0.014). Our findings indicate that GenX is a bioaccumulative compound, the presence of which likely inhibits the growth of plants.

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“…Studies have found that PFOS is widespread in various environmental media around the world, and is hazardous to biological health and the ecological environment, so the production and use of PFOS and its derivatives have been restricted or banned in several countries and regions [ 1 , 5 , 6 , 7 , 8 , 9 ]. However, because the application of PFOS in industrial production and daily life is considered essential, PFOS alternatives have been developed [ 10 , 11 , 12 , 13 ]. The use of 6:2 fluorotelomer sulfonate (6:2 FTSA) as a substitute represents an improvement on the structure of PFOS, replacing part of the C-F bond with a C-H bond to improve water solubility while ensuring similar physical and chemical properties to PFOS, and is currently being used as a PFOS replacement on a large scale in the European market [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Immunotoxicity and Transcriptome Analyses of Zebrafish (Danio rerio) Embryos Exposed to 6:2 FTSA

Zhang

Ren

Chen

2023

Toxics

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As a new alternative to perfluorooctane sulfonic acid (PFOS), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) has been widely produced and used in recent years, and its concentration and frequency of detection in the aquatic environment and aquatic organisms are increasing. However, studies of its toxicity in aquatic biological systems are alarmingly scarce, and the relevant toxicological information needs to be improved. In this study, we investigated AB wild-type zebrafish (Danio rerio) embryos subjected to acute 6:2 FTSA exposure for immunotoxicity using immunoassays and transcriptomics. Immune indexes showed significant decreases in SOD and LZM activities, but no significant change in NO content. Other indexes (TNOS, iNOS, ACP, AKP activities, and MDA, IL-1β, TNF-α, NF-κB, TLR4 content) all showed significant increases. These results indicated that 6:2 FTSA induced oxidative stress and inflammatory responses in zebrafish embryos and exhibited immunotoxicity. Consistently, transcriptomics showed that genes involved in the MAPK, TLR and NOD-like receptor signaling pathways (hsp70, hsp701, stat1b, irf3, cxcl8b, map3k8, il1b, tnfa and nfkb) were significantly upregulated after 6:2 FTSA exposure, suggesting that 6:2 FTSA might induce immunotoxicity in zebrafish embryos through the TLR/NOD-MAPK pathway. The results of this study indicate that the safety of 6:2 FTSA should be examined further.

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Hexafluoropropylene oxide dimer acid (GenX) exposure induces apoptosis in HepG2 cells

Cited by 14 publications

References 53 publications

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

GenX uptake by wheat and rice in flooded and non-flooded soils: a greenhouse experiment

Immunotoxicity and Transcriptome Analyses of Zebrafish (Danio rerio) Embryos Exposed to 6:2 FTSA

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