Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China.
Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, PR China; Institute of Yunnan Circular Agricultural Industry, Puer 665000, PR China.
Ecotoxicol Environ Saf. 2024 Oct 1;284:116877. doi: 10.1016/j.ecoenv.2024.116877. Epub 2024 Aug 13.
Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.
桔青霉素（CTN）是一种常见于污染食品和饲料中的真菌毒素，对人类和动物的健康都构成风险。然而，CTN 损伤肠道的机制尚不清楚。在本研究中，通过灌胃给予 6 周龄昆明小鼠 1.25mg/kg 和 5mg/kg CTN，连续 28 天，建立了肠道损伤模型，旨在探讨肠道损伤的潜在机制。结果表明，CTN 可导致小鼠空肠结构损伤。此外，CTN 降低 Claudin-1、Occludin、ZO-1 和 MUC2 的蛋白表达，从而破坏肠道的理化屏障。此外，CTN 改变了小鼠肠道微生物群的结构，从而损害了肠道微生物屏障。同时，研究结果表明，CTN 通过改变内质网中 CHOP 和 GRP78 以及线粒体中 Bax 和 Cyt c 等蛋白的表达，诱导肠道细胞过度凋亡。线粒体和内质网通过线粒体相关内质网膜（MAM）连接，调节膜。我们发现 CTN 处理后，膜上的桥接蛋白 Fis1 和 BAP31 的表达增加，这会加剧内质网功能障碍，并激活 Caspase-8 和 Bid 等蛋白，从而通过线粒体途径进一步诱导细胞凋亡。综上所述，这些结果表明 CTN 暴露可通过破坏肠道屏障和诱导肠道细胞过度凋亡引起肠道损伤。
