Zhang Shuhang, Zhang Yingqingqing, Yin Hai, Liu Yiling, Tang Lihui, Zhu Yanli, Sun Pinzhi, Wu Kexin, Zhao Baoyu, Lu Hao
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
Front Vet Sci. 2024 May 21;11:1387853. doi: 10.3389/fvets.2024.1387853. eCollection 2024.
Locoweed is a poisonous plant widely present in grasslands around the world. Swainsonine (SW), an indole alkaloid that, is the main toxic component of the locoweed. To understand the mechanism of SW-induced toxicity and to delineate the metabolic profile of locoweed poisoning we performed the LC-MS/MS untargeted metabolomic study to analyze metabolites in SW-treated renal tubular epithelial cells (0.8 mg/mL, 12 h) and in order to identify the SW-induced metabolomic changes. The analysis identified 2,563 metabolites in positive ion mode and 1,990 metabolites in negative ion mode. Our results showed that the metabolites were mainly benzenoids, lipids and lipid-like molecules, nucleosides, nucleotides, and analogs, organic acids, and derivatives. The differential metabolites were primarily enriched in pathways involving bile secretion, primary bile acid biosynthesis, riboflavin metabolism, ferroptosis, drug metabolism-cytochrome P450, and primidine metabolism. We have screened out substances such as swainsonine, 3alpha,7alpha-Dihydroxy-5beta-cholestanate, 2-Hydroxyiminostilbene, and glycochenodeoxycholate, which may have the potential to serve as biomarkers for swainsonine poisoning. This study provides insights into the types of metabolomic alteration in renal tubular epithelial cells induced by swainsonine.
疯草是一种广泛存在于世界各地草原的有毒植物。苦马豆素（SW）是一种吲哚生物碱，是疯草的主要有毒成分。为了解SW诱导毒性的机制并描绘疯草中毒的代谢谱，我们进行了液相色谱-串联质谱非靶向代谢组学研究，以分析经SW处理的肾小管上皮细胞（0.8mg/mL，12小时）中的代谢物，从而确定SW诱导的代谢组学变化。分析在正离子模式下鉴定出2563种代谢物，在负离子模式下鉴定出1990种代谢物。我们的结果表明，这些代谢物主要是苯类、脂质和类脂分子、核苷、核苷酸及其类似物、有机酸及其衍生物。差异代谢物主要富集在涉及胆汁分泌、初级胆汁酸生物合成、核黄素代谢、铁死亡、药物代谢-细胞色素P450和嘧啶代谢的途径中。我们筛选出了苦马豆素、3α,7α-二羟基-5β-胆甾烷酸、2-羟基亚氨基芪和甘氨鹅去氧胆酸等物质，它们可能有潜力作为苦马豆素中毒的生物标志物。本研究为苦马豆素诱导的肾小管上皮细胞代谢组学改变的类型提供了见解。
