Aflatoxin G (AFG), a member of the aflatoxin family with cytotoxic and carcinogenic properties, is one of the most common mycotoxins occurring in various agricultural products, animal feed, and human foods and drinks worldwide. Epithelial cells in the gastrointestinal tract are the first line of defense against ingested mycotoxins. However, the toxicity of AFG to gastric epithelial cells (GECs) remains unclear. In this study, we explored whether and how AFG-induced gastric inflammation regulates cytochrome P450 to contribute to DNA damage in GECs. Oral administration of AFG induced gastric inflammation and DNA damage in mouse GECs associated with P450 2E1 (CYP2E1) upregulation. Treatment with the soluble TNF-α receptor sTNFR:Fc inhibited AFG-induced gastric inflammation, and reversed CYP2E1 upregulation and DNA damage in mouse GECs. TNF-α-mediated inflammation plays an important role in AFG-induced gastric cell damage. Using the human gastric cell line GES-1, AFG upregulated CYP2E1 through NF-κB, causing oxidative DNA damage in vitro. The cells were also treated with TNF-α and AFG to mimic AFG-induced TNF-α-mediated inflammation. TNF-α activated the NF-κB/CYP2E1 pathway to promote AFG activation, which enhanced DNA cellular damage in vitro. In conclusion, AFG ingestion induces TNF-α-mediated gastric inflammation, which upregulates CYP2E1 to promote AFG-induced DNA damage in GECs.
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| http://dx.doi.org/10.1016/j.fct.2023.113756 | DOI Listing |
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