Dual-Emissive Detection of ATP and Hypochlorite Ions for Monitoring Inflammation-Driven Liver Injury In Vitro and In Vivo,Analytical Chemistry

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Dual-Emissive Detection of ATP and Hypochlorite Ions for Monitoring Inflammation-Driven Liver Injury In Vitro and In Vivo
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-05-28 , DOI: 10.1021/acs.analchem.4c00270
Maxine Mambo Fortibui ₁ , Chaewon Park ₂ , Na Yoon Kim ₁ , Tae Hyun Kim ₂ , Min Hee Lee ₁

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Reactive oxygen species play a pivotal role in liver disease, contributing to severe liver damage and chronic inflammation. In liver injury driven by inflammation, adenosine-5′-triphosphate (ATP) and hypochlorite ion (ClO^–) emerge as novel biomarkers, reflecting mitochondrial dysfunction and amplified oxidative stress, respectively. However, the dynamic fluctuations of ATP and ClO^– in hepatocytes and mouse livers remain unclear, and multidetection techniques for these biomarkers are yet to be developed. This study presents RATP-NClO, a dual-channel fluorescent bioprobe capable of synchronously detecting ATP and ClO^– ions. RATP-NClO exhibits excellent selectivity and sensitivity for ATP and ClO^– ions, demonstrating a dual-channel fluorescence response in a murine hepatocyte cell line. Upon intravenous administration, RATP-NClO reveals synchronized ATP depletion and ClO^– amplification in the livers of mice with experimental metabolic dysfunction-associated steatohepatitis (MASH). Through a comprehensive analysis of the principal mechanism of the developed bioprobe and the verification of its reliable detection ability in both in vitro and in vivo settings, we propose it as a unique tool for monitoring changes in intracellular ATP and ClO^– level. These findings underscore its potential for practical image-based monitoring and functional phenotyping of MASH pathogenesis.

中文翻译：

ATP 和次氯酸根离子的双发射检测用于监测体外和体内炎症驱动的肝损伤

活性氧在肝脏疾病中发挥着关键作用，导致严重的肝脏损伤和慢性炎症。在炎症驱动的肝损伤中，5'-三磷酸腺苷 (ATP) 和次氯酸根离子 (ClO ^– ) 成为新型生物标志物，分别反映线粒体功能障碍和放大的氧化应激。然而，肝细胞和小鼠肝脏^中ATP 和 ClO 的动态波动仍不清楚，并且这些生物标志物的多重检测技术仍有待开发。本研究提出了RATP-NClO ，一种能够同步检测 ATP 和 ClO ^-离子的双通道荧光生物探针。 RATP-NClO对 ATP 和 ClO ^-离子表现出优异的选择性和灵敏度，在鼠肝细胞系中表现出双通道荧光响应。静脉注射后， RATP-NClO显示患有实验性代谢功能障碍相关脂肪性肝炎 (MASH) 的小鼠肝脏中同步 ATP 消耗和^ClO扩增。通过对所开发的生物探针的主要机制进行全面分析并验证其在体外和体内环境中可靠的检测能力，我们建议将其作为监测细胞内 ATP 和 ClO^水平变化的独特工具。这些发现强调了其在基于图像的实用监测和 MASH 发病机制功能表型分析方面的潜力。

更新日期：2024-05-28

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