Laboratory of Genetic Breeding, Reproduction and Precision Livestock Farming & Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Laboratory of Genetic Breeding, Reproduction and Precision Livestock Farming & Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Ecotoxicol Environ Saf. 2024 Nov 1;286:117243. doi: 10.1016/j.ecoenv.2024.117243. Epub 2024 Oct 23.
Deoxynivalenol (DON) is a common fungal toxin that poses significant health risks to humans and animals. The present study aimed to investigate the adverse effects and molecular mechanisms of DON-induced kidney injury.
Male C57BL/6 mice aged 5-6 weeks were used to establish a DON-induced acute kidney injury model. Histological analysis, biochemical assays, molecular techniques, Western blot, RNA sequencing, and transmission electron microscopy were employed to analyze kidney damage, inflammation, oxidative stress, apoptosis, and endoplasmic reticulum (ER) stress.
DON disrupted kidney morphology, induced inflammatory cell infiltration, and triggered inflammatory responses. DON increased MDA content while decreasing antioxidant enzyme activity (SOD and CAT). It also triggered apoptosis, evidenced by elevated levels of caspase-12, cleaved caspase-3, and BAX, and reduced levels of Bcl-2. Transcriptomic analysis identified distinct expression patterns in 1756 genes in DON-exposed mouse kidneys, notably upregulating ER stress-related genes. Further investigation revealed ultrastructural changes in the ER and mitochondrial damage induced by DON, along with increased levels of p-IRE1, p-PERK, and their downstream targets, indicating unfolded protein response (UPR) activation in the kidney. The ER stress inhibitor 4-Phenylbutyric acid (4-PBA) significantly mitigated DON-induced ER stress, oxidative damage, apoptosis, tissue injury, ER expansion, and mitochondrial damage.
Our findings highlight the role of ER stress in DON-induced kidney injury and the protective effect of 4-PBA against these adverse effects.
脱氧雪腐镰刀菌烯醇（DON）是一种常见的真菌毒素，对人类和动物的健康构成重大威胁。本研究旨在探讨 DON 诱导的肾损伤的不良影响和分子机制。
使用 5-6 周龄雄性 C57BL/6 小鼠建立 DON 诱导的急性肾损伤模型。采用组织学分析、生化测定、分子技术、Western blot、RNA 测序和透射电镜观察来分析肾脏损伤、炎症、氧化应激、细胞凋亡和内质网（ER）应激。
DON 破坏了肾脏形态，诱导了炎症细胞浸润，并引发了炎症反应。DON 增加了 MDA 含量，降低了抗氧化酶活性（SOD 和 CAT）。它还触发了细胞凋亡，证据是 caspase-12、cleaved caspase-3 和 BAX 水平升高，Bcl-2 水平降低。转录组分析鉴定出 DON 暴露的小鼠肾脏中 1756 个基因的明显表达模式，特别是上调了与 ER 应激相关的基因。进一步研究发现，DON 诱导了内质网和线粒体损伤，内质网出现超微结构改变，同时 p-IRE1、p-PERK 及其下游靶点水平升高，表明肾脏中未折叠蛋白反应（UPR）被激活。内质网应激抑制剂 4-苯丁酸（4-PBA）显著减轻了 DON 诱导的 ER 应激、氧化损伤、细胞凋亡、组织损伤、内质网扩张和线粒体损伤。
我们的研究结果强调了 ER 应激在 DON 诱导的肾损伤中的作用，以及 4-PBA 对这些不良影响的保护作用。
