Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI. We designed a probe based on the ICT mechanism for the purpose of measuring and visualizing ONOO in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury. This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI.

中文翻译：

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使用近红外荧光探针对铁死亡介导的药物性肝损伤进行过氧亚硝酸盐成像


过量服用药物会导致药物性肝损伤 (DILI)，从而加重肝功能衰竭。大量研究表明铁死亡在 DILI 的病理生理学中发挥着重要作用，其特点是脂质活性氧 (ROS) 的产生和分解之间的显着不平衡。在此过程中过氧亚硝酸盐（ONOO）的含量迅速增加，被认为是早期肝损伤的重要标志。因此，构建用于ONOO检测和成像的荧光探针对于铁死亡介导的DILI的早期诊断和治疗具有重要意义。我们设计了一种基于 ICT 机制的探针，用于测量和可视化铁死亡介导的 DILI 过程中的 ONOO 及相关研究。该探针表现出显着的荧光变化，具有良好的灵敏度和选择性，并且可以对细胞内的外源性和内源性ONOO进行成像，且细胞毒性较低。使用该探针，我们能够显示由对乙酰氨基酚 (APAP) 和异烟肼 (INH) 干预诱导的铁死亡介导的 DILI 细胞和小鼠模型中 ONOO 含量的变化。通过测量小鼠肝组织中铁死亡相关指标的浓度，我们能够验证铁死亡在DILI中的作用。值得一提的是，与现有的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）检测方法相比，该探针可以实现在严重肝损伤之前早期识别DILI。该工作对于研究铁死亡与DILI的关系以及可视化研究具有重要的参考价值。结果表明 DILI 的进展与铁死亡之间存在很强的相关性。 此外，它的使用在研究 DILI 过程和评估药物治疗 DILI 的有效性方面显示出希望。