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一种具有新识别位点的红色荧光探针,用于追踪药物性肝损伤模型中生物硫醇的波动。

A red fluorescent probe with new recognition site for tracking the fluctuation of biothiol in drug-induced liver injury model.

作者信息

Shi Suntao, Shen Ruipeng, Mi Liangying, Hao Junlei, Sayed Zahid Nasim, Ma Zhengyu, Sun Chunlin, Wu Jiang, Zhang Haijuan, Zhang Baoxin

机构信息

State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China.

State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China; Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai Minzu University, Xining, Qinghai, 810007, China.

出版信息

Anal Chim Acta. 2025 Oct 1;1369:344364. doi: 10.1016/j.aca.2025.344364. Epub 2025 Jun 24.

DOI:10.1016/j.aca.2025.344364
PMID:40701707
Abstract

BACKGROUND

Drug-induced liver injury (DILI), which results from pharmaceuticals or their metabolites, is intricately associated with oxidative stress and is the most common liver disease. Biothiols play pivotal roles in maintaining redox homeostasis, cellular signalling, and cell growth. Moreover, alterations in biothiols levels are closely correlated with various health complications triggered by oxidative stress, including cardiovascular disorders, neurodegenerative diseases, and cancer. Consequently, developing strategies for the rapid and accurate detection of biothiols has garnered significant attention in clinical diagnostics.

RESULTS

Based on our previous work, we have rationally constructed a novel activatable red-emitting fluorescent probe featuring α, β-unsaturated acrylate as a recognition unit for the detection of biological thiols for the first time. Upon reaction with biothiols, the probe exhibits significant fluorescence enhancement at 625 nm. Furthermore, the excellent selectivity, sensitivity, and low cytotoxicity of FR-10C establish it as a potent tool for biothiols detection in complex biological systems. Moreover, zebrafish experiments and the DILI mouse model were employed to evaluate the potential of FR-10C to detect biothiols in living organisms, which proved its sensitive detection ability of changes in biothiols level in dynamic biological environments.

SIGNIFICANCE

The successful design of this probe has unveiled a promising avenue for advancing thiol-activatable fluorescent probes which highlights the potential of the α, β-unsaturated acrylate unit as a novel and specific recognition moiety for thiols.

摘要

背景

药物性肝损伤(DILI)由药物及其代谢产物引起,与氧化应激密切相关,是最常见的肝脏疾病。生物硫醇在维持氧化还原稳态、细胞信号传导和细胞生长中起关键作用。此外,生物硫醇水平的改变与氧化应激引发的各种健康并发症密切相关,包括心血管疾病、神经退行性疾病和癌症。因此,开发快速准确检测生物硫醇的策略在临床诊断中备受关注。

结果

基于我们之前的工作,我们首次合理构建了一种新型可激活的红色荧光探针,该探针以α,β-不饱和丙烯酸酯作为识别单元用于检测生物硫醇。与生物硫醇反应后,该探针在625nm处表现出显著的荧光增强。此外,FR-10C优异的选择性、灵敏度和低细胞毒性使其成为复杂生物系统中生物硫醇检测的有力工具。此外,利用斑马鱼实验和DILI小鼠模型评估了FR-10C在活生物体中检测生物硫醇的潜力,证明了其对动态生物环境中生物硫醇水平变化的灵敏检测能力。

意义

该探针的成功设计为推进硫醇可激活荧光探针开辟了一条有前景的途径,突出了α,β-不饱和丙烯酸酯单元作为硫醇新型特异性识别部分的潜力。

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