Zhang Xinxin, Gu Lepeng, Chen Ying, Wang Tianqi, Xing Houjuan
College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People's Republic of China.
College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, People's Republic of China; Key Laboratory of Swine Facilities Engineering, Ministry of Agriculture and Rural Affairs, Northeast Agricultural University, Harbin 150030, People's Republic of China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117477. doi: 10.1016/j.ecoenv.2024.117477. Epub 2024 Dec 9.
Ammonia is an important component of PM2.5 and PM10, and is also a major harmful gas in intensive and large-scale pig houses, which poses a potential threat to the health of farmers and animals. Intestinal tract is the largest immune organ in the body and is also an important target organ for ammonia exposure. However, the potential toxicity mechanism of ammonia exposure to the intestine remains unclear. L-selenomethionine is an important source of organic selenium with the advantages of high bioavailability, safety and high efficiency. In order to explore the mechanism of ammonia enterotoxicity and the mitigation effect of L-selenomethionine on ammonia enterotoxicity, multi-dimensional ammonia toxicity models and L-selenomethionine intervention models were established in vivo and in vitro. The results showed that ammonia exposure up-regulated the levels of iron, ROS, MDA, and LPO in the small intestinal tissue and the IPEC-J2 cell, down-regulated the activities of antioxidant enzymes and the content of GSH, inhibited the Nrf2 pathway, significantly altered the expression of ferroptosis (TFR-1, FPN-1, FTH1, SLC7A11, GPX4, ACSL4) and intestine tight junctions (Claudin-1, Occludin, ZO-1) genes. Compared with the ammonia exposure group, L-selenomethionine group could significantly improve the changes of these ferroptosis indicators by affecting ROS and iron levels through Nrf2 pathway. Our results indicated that L-selenomethionine inhibited small intestinal epithelial cells ferroptosis caused by ammonia exposure through regulating ROS-mediated iron metabolism.
氨是细颗粒物（PM2.5）和可吸入颗粒物（PM10）的重要组成部分，也是集约化大型养猪场中的主要有害气体，对养殖户和动物的健康构成潜在威胁。肠道是人体最大的免疫器官，也是氨暴露的重要靶器官。然而，氨暴露对肠道的潜在毒性机制尚不清楚。L-硒代蛋氨酸是有机硒的重要来源，具有生物利用度高、安全高效等优点。为了探究氨肠毒性的机制以及L-硒代蛋氨酸对氨肠毒性的缓解作用，在体内和体外建立了多维氨毒性模型和L-硒代蛋氨酸干预模型。结果表明，氨暴露上调了小肠组织和IPEC-J2细胞中铁、活性氧（ROS）、丙二醛（MDA）和脂质过氧化物（LPO）的水平，下调了抗氧化酶活性和谷胱甘肽（GSH）含量，抑制了核因子E2相关因子2（Nrf2）通路，显著改变了铁死亡相关基因（转铁蛋白受体1、铁转运蛋白1、铁蛋白重链1、溶质载体家族7成员11、谷胱甘肽过氧化物酶4、长链脂酰辅酶A合成酶4）和肠道紧密连接相关基因（闭合蛋白1、闭锁蛋白、紧密连接蛋白1）的表达。与氨暴露组相比，L-硒代蛋氨酸组可通过Nrf2通路影响ROS和铁水平，显著改善这些铁死亡指标的变化。我们的结果表明，L-硒代蛋氨酸通过调节ROS介导的铁代谢抑制氨暴露引起的小肠上皮细胞铁死亡。
