Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Department of Pharmaceutical Sciences, School of Medicine, Wayne State University, Detroit, MI, 48201, USA.
Toxicon. 2024 Mar;240:107633. doi: 10.1016/j.toxicon.2024.107633. Epub 2024 Feb 6.
As a global toxin invasive species, the whole herb of Ageratina adenophora (A. adenophora) contains various sesquiterpenes, which can cause various degrees of toxic reactions characterized by inflammatory damage when ingested by animals. Current studies on the toxicity of A. adenophora have focused on parenchymatous organs such as the liver and spleen, but few studies have been conducted on the intestine as the organ that is first exposed to A. adenophora and digests and absorbs its toxic components. In this study, after feeding goats with 40 % A. adenophora herb powder for 90 d, we found that the intestinal structure of goats showed pathological changes characterized, and the damage to the small intestinal segments was more severe than that of the large intestine. The MLCK/ROCK signaling pathway was activated, the cytoskeleton underwent centripetal contraction, the composition of tight junctions between intestinal epithelial cells was altered table, Occludin, Claudin-1 and Zonula occluden (ZO-1) amount was decreased, and the intestinal mechanical barrier was disrupted. The intestinal damage markers diamine oxidase (DAO) and D-lactate (D-LA) levels were elevated. In addition, we also found that intestinal bacteria translocate and enter the portal vein to colonize the liver and mesenteric lymph nodes. The expression of intestinal pro-inflammatory factors and anti-inflammatory factors was changed, the intestinal immune function was disrupted. The present study is the first to analyze the mechanism of poisoning of A. adenophora from the intestinal tract in compound-gastric animals.
作为一种全球性的入侵毒草,紫茎泽兰(A. adenophora)全草含有各种倍半萜类化合物,当动物摄入这些化合物时,会引起各种程度的以炎症损伤为特征的毒性反应。目前对紫茎泽兰毒性的研究主要集中在肝、脾等实质器官,但对肠道的研究较少,肠道是首先接触到紫茎泽兰并消化和吸收其有毒成分的器官。在本研究中,我们用 40%紫茎泽兰草粉喂养山羊 90 天后发现,山羊的肠道结构出现了病变特征,且小肠段的损伤比大肠段更严重。MLCK/ROCK 信号通路被激活,细胞骨架向心收缩,肠上皮细胞之间紧密连接的组成发生改变,Occludin、Claudin-1 和 Zonula occluden(ZO-1)的含量减少,肠道机械屏障被破坏。肠道损伤标志物二胺氧化酶(DAO)和 D-乳酸(D-LA)水平升高。此外,我们还发现肠道细菌易位并进入门静脉定植于肝脏和肠系膜淋巴结。肠道促炎因子和抗炎因子的表达发生改变,肠道免疫功能受到破坏。本研究首次从复合胃动物的肠道角度分析了紫茎泽兰中毒的机制。