Xie Peisi, Chen Jing, Xia Yongjun, Lin Zian, He Yu, Cai Zongwei
Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, 350116, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, 999077, China.
J Pharm Anal. 2024 Nov;14(11):101024. doi: 10.1016/j.jpha.2024.101024. Epub 2024 Jun 26.
Triclocarban (TCC) is a common antimicrobial agent that has been widely used in medical care. Given the close association between TCC treatment and metabolic disorders, we assessed whether long-term treatment to TCC at a human-relevant concentration could induce nephrotoxicity by disrupting the metabolic levels in a mouse model. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was applied to investigate the alterations in the spatial distributions and abundances of TCC, endogenous and exogenous metabolites in the kidney after TCC treatment. The results showed that TCC treatment induced the changes in the organ weight, organ coefficient and histopathology of the mouse kidney. MSI data revealed that TCC accumulated in all regions of the kidney, while its five metabolites mainly distributed in the cortex regions. The abundances of 79 biomolecules associated with pathways of leukotriene E4 metabolism, biosynthesis and degradation of glycerophospholipids and glycerolipids, ceramide-to-sphingomyelin signaling were significantly altered in the kidney after TCC treatment. These biomolecules showed distinctive distributions in the kidney and displayed a favorable spatial correlation with the pathological damage. This work offers new insights into the related mechanisms of TCC-induced nephrotocicity and exhibits the potential of MALDI-MSI-based spatial metabolomics as a promising approach for the risk assessment of agents in medical care.
三氯生（TCC）是一种常用的抗菌剂，已广泛应用于医疗保健领域。鉴于TCC治疗与代谢紊乱之间的密切关联，我们评估了在小鼠模型中，以与人体相关的浓度对TCC进行长期治疗是否会通过扰乱代谢水平而诱导肾毒性。应用基质辅助激光解吸/电离质谱成像（MALDI-MSI）技术来研究TCC治疗后肾脏中TCC、内源性和外源性代谢物的空间分布及丰度变化。结果表明，TCC治疗引起了小鼠肾脏的器官重量、器官系数和组织病理学变化。MSI数据显示，TCC在肾脏的所有区域均有积累，而其五种代谢物主要分布在皮质区域。TCC治疗后，肾脏中与白三烯E4代谢、甘油磷脂和甘油脂的生物合成及降解、神经酰胺到鞘磷脂信号传导途径相关的79种生物分子的丰度发生了显著变化。这些生物分子在肾脏中呈现出独特的分布，并与病理损伤表现出良好的空间相关性。这项工作为TCC诱导肾毒性的相关机制提供了新的见解，并展示了基于MALDI-MSI的空间代谢组学作为医疗保健中药物风险评估的一种有前景方法的潜力。
