Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice

文献类型： 外文期刊

第一作者： Fan, Shijie

作者： Fan, Shijie;Lin, Luxi;Li, Pingyang;Tian, Huihui;Shen, Jialu;Zhou, Longzhu;Zhao, Qingyu;Zhang, Junmin;Qin, Yuchang;Tang, Chaohua

作者机构：

关键词： Deoxynivalenol; Selenomethionine; Oxidation stress; Nrf2/PPAR gamma; Lipotoxicity; Ferroptosis

期刊名称：TOXICOLOGY （ 影响因子：4.5； 五年影响因子：4.6 ）

ISSN： 0300-483X

年卷期： 2024 年 501 卷

页码：

收录情况： SCI

摘要： Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/ kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dis-mutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accu-mulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor gamma (PPAR gamma), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPAR gamma-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

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