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芦丁通过p53信号通路减轻玉米赤霉烯酮诱导的仔猪子宫内膜基质细胞铁死亡。

Rutin attenuates zearalenone-induced ferroptosis of endometrial stromal cells in piglets through the p53 signaling pathway.

作者信息

Wang Chenlong, Chen Chuangjiang, Wang MengYa, Rahman Sajid Ur, Wei Bin, Ding Hongyan, Huang Wanyue, Wang Xichun

机构信息

College of Veterinary Medicine, Anhui Agricultural University, Hefei 230036, China.

Huangyuan County Animal Husbandry and Veterinary Station, Xining, Qinghai 812100, China.

出版信息

Ecotoxicol Environ Saf. 2025 Jan 15;290:117546. doi: 10.1016/j.ecoenv.2024.117546. Epub 2024 Dec 18.

DOI:10.1016/j.ecoenv.2024.117546
PMID:39700772
Abstract

Zearalenone (ZEA) is an environmentally widespread mycotoxin capable of posing a serious threat to food safety and public health, and porcine endometrial stromal cells (ESCs) are particularly sensitive to the toxic effects of ZEA. We hypothesized that Rutin, a flavonoid antioxidant, could significantly alleviate ZEA-induced ferroptosis through the p53 signaling pathway. In this study, we used porcine ESCs as a research model. When porcine ESCs were co-cultured with the addition of Rutin and ZEA following p53 gene silencing via siRNA transfection, Rutin significantly mitigated ZEA-induced mitochondrial damage, oxidative stress, and Fe content through the p53 pathway. Additionally Rutin lowered the expression of p53, ALOX12, and ACSL4 while significantly improving cytokinesis, antioxidant enzyme activity, and SLC7A11, GPX4, Nrf2, FTH1, thereby inhibiting cellular ferroptosis. These findings suggested a novel programmed death mechanism for alleviating the cytotoxic effects of ZEA, involving the knockdown of p53.

摘要

玉米赤霉烯酮(ZEA)是一种在环境中广泛存在的霉菌毒素,能够对食品安全和公众健康构成严重威胁,而猪子宫内膜基质细胞(ESCs)对ZEA的毒性作用尤为敏感。我们假设,黄酮类抗氧化剂芦丁可通过p53信号通路显著减轻ZEA诱导的铁死亡。在本研究中,我们使用猪ESCs作为研究模型。当通过siRNA转染沉默p53基因后,将猪ESCs与芦丁和ZEA共同培养时,芦丁通过p53途径显著减轻了ZEA诱导的线粒体损伤、氧化应激和铁含量。此外,芦丁降低了p53、ALOX12和ACSL4的表达,同时显著改善了细胞分裂、抗氧化酶活性以及SLC7A11、GPX4、Nrf2、FTH1的水平,从而抑制细胞铁死亡。这些发现提示了一种减轻ZEA细胞毒性作用的新型程序性死亡机制,涉及p53的敲低。

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Rutin attenuates zearalenone-induced ferroptosis of endometrial stromal cells in piglets through the p53 signaling pathway.芦丁通过p53信号通路减轻玉米赤霉烯酮诱导的仔猪子宫内膜基质细胞铁死亡。
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