Decabromodiphenyl ether induces ROS‐mediated intestinal toxicity through the Keap1‐Nrf2 pathway

Li, Shiqi; Yuan, Jinwen; Che, Siyan; Zhang, Li; Ruan, Zheng; Sun, Xiaoming

doi:10.1002/jbt.22995

Cited by 10 publications

(2 citation statements)

References 68 publications

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“…Coexposure of TCDD and PBDE209 was observed in 33% of the omentum from patients with diffuse GC. Interestingly, an increased incidence of hepatocellular carcinomas was observed in rodents upon exposure to PBDE-209 as well as an increased CYP1A1 mRNA expression levels in Caco-2 cells [65].…”

Section: Discussionmentioning

confidence: 99%

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Perrot-Applanat,

Pimpie,

Vacher

et al. 2024

Preprint

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Diffuse type of gastric cancer (GC) has an increasing prevalence worldwide, especially in Western countries, is usually diagnosed at advanced stages, and has no efficacious treatment options. Epidemiological studies have reported an increased mortality from GC after occupational exposure to well-studied pro-carcinogen that are metabolically activated by Cyp P450 enzymes through aryl hydrocarbon receptor (AhR). Substantial studies support the involvement of AhR in gastric carcinogenesis. However, little is known about the role of AhR in diffuse GC, as compared to intestinal GC. In a cohort of 29 gastric tumors, we described a significantly increased AhR protein and mRNA expression levels in GCs, independently of subtypes and clinical parameters. AhR and RhoA mRNA expression were correlated in diffuse GC. Further, our study characterized how AhR affects gene expression in diffuse GC. Using qRT-PCR, we compared the expression levels of AhR, Cyp1A1 and Cyp1B1 to the expression of genes in a panel previously described. In diffuse GC, Cyp1A1 expression correlated with genes involved in IGF signalling, EMT (VIM), migration (MMP2). In an in vitro assay using the poorly differentiated KATOIII epithelial cell line, two well-known ligands for AhR (TCDD and BaP) induced mRNA expression of CYP1A1, IL1b, as well as UGT1, NQO1 and AhRR to a lower extent. We also observed a strong increase in Cyp1B1 expression in diffuse GC, along with a lower TCDD-increased Cyp1B1 expression as compared to Cyp1A1 in KATOIII cells, and immunostaining in stromal cells. In intestinal GC, Cyp1B1 inversely correlated with several genes including IDO1 (generating endogenous kynurenin-e AhR ligand). Our data provide evidence for a major role of AhR in GC, as an environmental xenobiotics receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support continued efforts to clarify the identities of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Perrot-Applanat,

Pimpie,

Vacher

et al. 2024

Preprint

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“…The mRNA expression of the antioxidative defense factor, Nrf2, was suppressed by PBDE-209. Besides, Caco-2 cells exposed to PBDE-209 exhibited a rise in Fas cell surface death receptor (FAS) and CYP1A1 mRNA expression levels [98]. The mechanisms are shown in Figures 2 and 3.…”

Section: Gut Toxicity 41 Oxidative Damage and Apoptosismentioning

confidence: 96%

Toxic Effects and Mechanisms of Polybrominated Diphenyl Ethers

Xue,

Xiao,

Zhang

et al. 2023

IJMS

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Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants used in plastics, textiles, polyurethane foam, and other materials. They contain two halogenated aromatic rings bonded by an ester bond and are classified according to the number and position of bromine atoms. Due to their widespread use, PBDEs have been detected in soil, air, water, dust, and animal tissues. Besides, PBDEs have been found in various tissues, including liver, kidney, adipose, brain, breast milk and plasma. The continued accumulation of PBDEs has raised concerns about their potential toxicity, including hepatotoxicity, kidney toxicity, gut toxicity, thyroid toxicity, embryotoxicity, reproductive toxicity, neurotoxicity, and immunotoxicity. Previous studies have suggested that there may be various mechanisms contributing to PBDEs toxicity. The present study aimed to outline PBDEs’ toxic effects and mechanisms on different organ systems. Given PBDEs’ bioaccumulation and adverse impacts on human health and other living organisms, we summarize PBDEs’ effects and potential toxicity mechanisms and tend to broaden the horizons to facilitate the design of new prevention strategies for PBDEs-induced toxicity.

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Association between brominated flame retardants exposure and markers of oxidative stress in US adults: An analysis based on the National Health and Nutrition Examination Survey 2007–2016

Han

Wang

2023

Ecotoxicology and Environmental Safety

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Decabromodiphenyl ether induces ROS‐mediated intestinal toxicity through the Keap1‐Nrf2 pathway

Cited by 10 publications

References 68 publications

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Toxic Effects and Mechanisms of Polybrominated Diphenyl Ethers

Association between brominated flame retardants exposure and markers of oxidative stress in US adults: An analysis based on the National Health and Nutrition Examination Survey 2007–2016

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