Revealing a close link between ferroptosis and drug-induced liver injury with dual-site NIR ratiometric fluorescent probe for mitochondrial peroxynitrite

IF 3.7 1区化学 Q1 CHEMISTRY, ANALYTICAL

Sensors and Actuators B: Chemical Pub Date : 2025-10-13 DOI:10.1016/j.snb.2025.138985

Zhengliang Lu , Xionghao Xu , Bo Zhao , Tao Jiang , Tianxin Liu , Won Jun Jang , Juyoung Yoon , Mei Yan , Chunhua Fan

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Abstract

Drug-induced liver injury (DILI) is a clinically prevalent condition, one of whose pathogenic mechanisms involves overdose or dependent use of drugs such as acetaminophen (APAP). Although ferroptosis-driven by iron metabolism dysregulation and lipid peroxidation accumulation-has been extensively investigated, the theroretical basis for diagnosing DILI remains insufficient. To explore the correlation between DILI and ferroptosis, we developed a dual-reactive-site mitochondria-targeted near-infrared (NIR) ratiometric fluorescent probe (Mito-Rh-B2) for detecting ONOO^–. Mito-Rh-B2 not only differentiated between various drug-induced DILI types but also successfully revealed a dose-dependent increase in ONOO^– level in an APAP-induced DILI model. Furthermore, cell experiments demonstrated a strong association between ONOO^–/GSH level and both DILI and ferroptosis. This study provides new insights for future clinical applications related to DILI and ferroptosis.

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线粒体过氧亚硝酸盐双位点近红外比例荧光探针揭示铁下垂与药物性肝损伤之间的密切联系

药物性肝损伤（DILI）是一种临床上普遍存在的疾病，其致病机制之一涉及对乙酰氨基酚（APAP）等药物的过量或依赖使用。虽然由铁代谢失调和脂质过氧化积累引起的死铁已被广泛研究，但诊断DILI的理论基础仍然不足。为了探讨DILI与铁死亡之间的相关性，我们开发了一种双反应位点线粒体靶向近红外（NIR）比例荧光探针（Mito-Rh-B2）用于检测ONOO -。Mito-Rh-B2不仅在多种药物诱导的DILI类型之间存在分化，而且在apap诱导的DILI模型中成功显示出ONOO -水平的剂量依赖性增加。此外，细胞实验表明ONOO - /GSH水平与DILI和铁下垂有很强的相关性。本研究为DILI和铁下垂的临床应用提供了新的见解。

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来源期刊

Sensors and Actuators B: Chemical 工程技术-电化学

CiteScore

14.60

自引率

11.90%

发文量

1776

审稿时长

3.2 months

期刊介绍： Sensors & Actuators, B: Chemical is an international journal focused on the research and development of chemical transducers. It covers chemical sensors and biosensors, chemical actuators, and analytical microsystems. The journal is interdisciplinary, aiming to publish original works showcasing substantial advancements beyond the current state of the art in these fields, with practical applicability to solving meaningful analytical problems. Review articles are accepted by invitation from an Editor of the journal.