对复杂生物系统内药物积累的检查为药物代谢和毒性的分子方面提供了宝贵的见解。基质辅助激光解吸/电离质谱成像（MALDI MSI）是一种创新方法，可实现复杂生物系统中生物分子以及药物及其代谢物的空间可视化和定量。因此，该方法为代谢概况和药物治疗可能发生的任何分子变化提供了有价值的见解。肾脏系统特别容易受到药物引起的伤害和毒性的不利影响。在这项研究中，MALDI MSI 用于检查单次口服抗癌化合物鱼藤酮后药物和肾脏代谢物在肾组织内的空间分布。离子迁移谱与 MALDI MSI 的集成增强了数据采集和分析，从而提高了质量分辨率。随后，使用 MALDI HDMS/MS 成像检测并表征鱼藤酮参比药物的 MS/MS 碎片离子。值得注意的是，在用鱼藤酮处理的代表性肾组织切片的皮质区域中观察到药物蓄积。处理后的肾组织的组织学检查没有发现任何可观察到的变化。在未处理和鱼藤酮处理的组织之间观察到肾内源性代谢物的差异离子强度。在经过处理的肾组织中，与未经处理的肾组织相比，鞘磷脂 (D18:1/16:0)（肾小球细胞损伤和肾损伤的鞘脂指标）的离子强度水平显着升高。相反，胆碱、甘油-3-磷酸胆碱(GPC)、肌苷和溶血磷脂酰胆碱LysoPC(18:0)的离子强度表现出显着降低。这项研究的结果证明了 MALDI MSI 作为一种新技术的潜力，用于研究药物和肾内源性分子的原位空间分布，同时保留肾组织的解剖完整性。该技术可用于以动态方式研究药物诱导的代谢和毒性。版权所有 © 2024 Tenebro、Marcial、Salcepuedes、Torrecampo、Hernandez、Francisco、Infante、Belardo、Paderes、Alvero、Saludes 和 Dalisay。

The examination of drug accumulation within complex biological systems offers valuable insights into the molecular aspects of drug metabolism and toxicity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an innovative methodology that enables the spatial visualization and quantification of biomolecules as well as drug and its metabolites in complex biological system. Hence, this method provides valuable insights into the metabolic profile and any molecular changes that may occur as a result of drug treatment. The renal system is particularly vulnerable to adverse effects of drug-induced harm and toxicity. In this study, MALDI MSI was utilized to examine the spatial distribution of drug and renal metabolites within kidney tissues subsequent to a single oral dosage of the anticancer compound rotenone. The integration of ion mobility spectrometry with MALDI MSI enhanced the data acquisition and analysis, resulting to improved mass resolution. Subsequently, the MS/MS fragment ions of rotenone reference drug were detected and characterized using MALDI HDMS/MS imaging. Notably, drug accumulation was observed in the cortical region of the representative kidney tissue sections treated with rotenone. The histological examination of treated kidney tissues did not reveal any observable changes. Differential ion intensity of renal endogenous metabolites was observed between untreated and rotenone-treated tissues. In the context of treated kidney tissues, the ion intensity level of sphingomyelin (D18:1/16:0), a sphingolipid indicator of glomerular cell injury and renal damage, was found to be elevated significantly compared to untreated kidney tissues. Conversely, the ion intensities of choline, glycero-3-phosphocholine (GPC), inosine, and a lysophosphatidylcholine LysoPC(18:0) exhibited a significant decrease. The results of this study demonstrate the potential of MALDI MSI as a novel technique for investigating the in situ spatial distribution of drugs and renal endogenous molecules while preserving the anatomical integrity of the kidney tissue. This technique can be used to study drug-induced metabolism and toxicity in a dynamic manner.Copyright © 2024 Tenebro, Marcial, Salcepuedes, Torrecampo, Hernandez, Francisco, Infante, Belardo, Paderes, Alvero, Saludes and Dalisay.