School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Key Laboratory of Molecular Animal Nutrition of the Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
Ecotoxicol Environ Saf. 2024 Oct 1;284:116914. doi: 10.1016/j.ecoenv.2024.116914. Epub 2024 Aug 24.
Selenium nanoparticles (SeNPs) have been used as a potential alternative to other forms of selenium in nutritional supplements for the treatment and prevention of inflammatory and oxidative stress-related diseases. Zearalenone (ZEA) is a foodborne mycotoxin present in grains that poses a health threat. Here, we investigated the adverse impacts of ZEA on intestinal homeostasis and explored the protective effects of probiotic-synthesized SeNPs against its damage. Results showed that ZEA reduced mucin and tight junction proteins expression in jejunum, induced inflammatory process and oxidative stress which in turn increased intestinal permeability in mice. ZEA-induced intestinal toxicity was further verified in vitro. Intracellular redox imbalance triggered endoplasmic reticulum (ER) stress in intestinal epithelial cells, which caused structural damage to the ER. Remarkably, SeNPs exhibited a counteractive effect by inducing a decrease in intracellular levels of Inositol 1,4,5-trisphosphate (IP3) and Ca, along with a reduction in the expression level of IP3 receptor. SeNPs effectively mitigated ZEA-induced ER stress was related to the increased activity of selenium-dependent antioxidant enzymes and the expression of ER-resident selenoproteins. Furthermore, SeNPs significantly inhibited the activation of PERK/eIF2α/ATF4/CHOP pathway in vitro and in vivo. In addition, SeNPs effectively reversed ZEA-induced gut microbiota dysbiosis and increased the abundance of short-chain fatty acid-producing beneficial bacteria (Alloprevotella and Muribaculaceae). The Spearman correlation analysis suggested that the structure of gut microbiota was closely related to the SeNPs attenuation of ZEA-induced intestinal toxicity. This study provides new insights into ZEA-induced intestinal toxicity and identifies a novel potential nutrient SeNPs to overcome adverse effects.
硒纳米颗粒（SeNPs）已被用作营养补充剂中替代其他形式硒的潜在替代品，用于治疗和预防炎症和氧化应激相关疾病。玉米赤霉烯酮（ZEA）是一种存在于谷物中的食源性真菌毒素，对健康构成威胁。在这里，我们研究了 ZEA 对肠道内稳态的不良影响，并探索了益生菌合成的 SeNPs 对其损伤的保护作用。结果表明，ZEA 降低了空肠中的粘蛋白和紧密连接蛋白表达，诱导了炎症过程和氧化应激，从而增加了小鼠的肠道通透性。ZEA 诱导的肠道毒性在体外也得到了进一步验证。细胞内氧化还原失衡触发了肠上皮细胞内质网（ER）应激，导致 ER 结构损伤。值得注意的是，SeNPs 通过诱导细胞内三磷酸肌醇（IP3）和 Ca 水平降低以及 IP3 受体表达水平降低，表现出拮抗作用。SeNPs 有效缓解 ZEA 诱导的 ER 应激与硒依赖性抗氧化酶活性的增加和 ER 驻留硒蛋白的表达有关。此外，SeNPs 显著抑制了 PERK/eIF2α/ATF4/CHOP 通路在体外和体内的激活。此外，SeNPs 有效逆转了 ZEA 引起的肠道微生物群失调，并增加了短链脂肪酸产生有益细菌（Alloprevotella 和 Muribaculaceae）的丰度。Spearman 相关性分析表明，肠道微生物群的结构与 SeNPs 减轻 ZEA 诱导的肠道毒性密切相关。本研究为 ZEA 诱导的肠道毒性提供了新的见解，并确定了一种新的潜在营养物 SeNPs 来克服其不良影响。
