Curcumin Can Inhibit Zearalenone-Induced Ferroptosis in Porcine Intestinal Epithelial Cells via the p53/SLC7A11/GPX4 Pathway.

IF 4.1 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Toxics Pub Date : 2025-08-24 DOI:10.3390/toxics13090713

Dongwei Xiong, Weidong Qi, Miao Long

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Abstract

Zearalenone (ZEA) is a widely distributed estrogenic mycotoxin that can disrupt intestinal barrier integrity by inducing ferroptosis, thereby posing serious risks to animal health. Curcumin (CUR), as a natural polyphenolic compound with multi-target regulatory properties, has attracted increasing attention for its antioxidative and cytoprotective effects; however, its role in ZEA-induced ferroptosis remains poorly understood. In this study, the protective effects of curcumin (CUR) were evaluated in IPEC-J2 cells by co-treating the cells with zearalenone (ZEA) at its LC₅₀ (75.23 μM) and curcumin (5 or 15 μM) for 24 h. CCK-8 assays showed that CUR significantly (p < 0.05) and highly significantly (p < 0.01) improved cell viability in the 5 μM and 15 μM groups, respectively, compared with ZEA alone. CUR co-treatment significantly (p < 0.01) restored glutathione (GSH) levels, and markedly (p < 0.01) reduced Fe²⁺ accumulation, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and lipid peroxidation (LPO). Transmission electron microscopy revealed pronounced mitochondrial cristae loss and membrane collapse in ZEA-treated cells, which were visibly alleviated by CUR. At the molecular level, ZEA downregulated GPX4 and SLC7A11 and upregulated ACSL4, FTH1, and p53 (all p < 0.01), whereas these changes were significantly reversed (p < 0.05 or p < 0.01) by CUR. In conclusion, CUR exerts cytoprotective effects against ZEA-induced ferroptosis, likely via modulation of the p53/SLC7A11/GPX4 signaling pathway.

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姜黄素可通过p53/SLC7A11/GPX4途径抑制玉米赤霉烯酮诱导的猪肠上皮细胞铁凋亡

玉米赤霉烯酮（ZEA）是一种广泛分布的雌激素性真菌毒素，可通过诱导铁下垂破坏肠道屏障的完整性，从而对动物健康构成严重风险。姜黄素（Curcumin， CUR）作为一种具有多靶点调控特性的天然多酚类化合物，因其抗氧化和细胞保护作用而受到越来越多的关注；然而，其在zea诱导的铁下垂中的作用仍然知之甚少。本研究通过与玉米赤霉烯酮（ZEA）（LC50为75.23 μM）和姜黄素（5 μM或15 μM）共处理IPEC-J2细胞24 h，评价姜黄素（CUR）对IPEC-J2细胞的保护作用。CCK-8实验显示，与单独处理ZEA相比，姜黄素在5 μM和15 μM组分别显著（p < 0.05）和极显著（p < 0.01）提高了IPEC-J2细胞的活力。CUR共处理显著（p < 0.01）恢复了谷胱甘肽（GSH）水平，显著（p < 0.01）降低了Fe2+积累、活性氧（ROS）产生、丙二醛（MDA）含量和脂质过氧化（LPO）。在分子水平上，ZEA可下调GPX4和SLC7A11的表达，上调ACSL4、FTH1和p53的表达（p < 0.01），而CUR可显著逆转这些变化（p < 0.05或p < 0.01），可见，CUR对ZEA诱导的铁下垂具有细胞保护作用。可能通过调节p53/SLC7A11/GPX4信号通路。

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来源期刊

Toxics Chemical Engineering-Chemical Health and Safety

CiteScore

4.50

自引率

10.90%

发文量

681

审稿时长

6 weeks

期刊介绍： Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.