New insights into the downregulation of cytochrome P450 2E1 via nuclear factor κB-dependent pathways in immune-mediated liver injury

Zou, Huiqiong; Cao, Yingying; Hao, Peipei; Jin, Ziqi; Ding, Ruifeng; Bai, Xuefeng; Zhang, Kun; Xue, Yongzhi

doi:10.1016/j.heliyon.2023.e22641

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…The liver is an important metabolic clearance organ in the human body and is also the most vulnerable organ to toxic damage. 32 When liver injury occurs, the levels of many biomarkers in the liver are altered, such as ALT, AST, and ALP. 33 In the present study, we found that AST, ALT, and ALP changed abnormally after GenX exposure, but there was no significant increase in ALP in a dose-dependent manner as found by Guo's team.…”

Section: Discussionmentioning

confidence: 99%

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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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The liver is an important metabolic clearance organ in the human body and is also the most vulnerable organ to toxic damage . When liver injury occurs, the levels of many biomarkers in the liver are altered, such as ALT, AST, and ALP .…”

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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Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma

Huang,

Zhong,

et al. 2024

Biomedicine & Pharmacotherapy

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New insights into the downregulation of cytochrome P450 2E1 via nuclear factor κB-dependent pathways in immune-mediated liver injury

Cited by 2 publications

References 32 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

Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma

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