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线粒体靶向比率型化学荧光探针用于检测次氯酸用于监测药物损伤的肝和肾

Mitochondria-Targeted Ratiometric Chemdosimeter to Detect Hypochlorite Acid for Monitoring the Drug-Damaged Liver and Kidney.

机构信息

School of Engineering, China Pharmaceutical University, Nanjing 211198, China.

Key Laboratory of Organo-Pharmaceutical Chemistry of Jiangxi Province, School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, China.

出版信息

Anal Chem. 2022 Aug 30;94(34):11881-11888. doi: 10.1021/acs.analchem.2c02431. Epub 2022 Aug 16.

Abstract

Liver and kidney injury caused by drug toxicity is a serious threat to human health. Acetaminophenol (APAP), as a common antipyretic and analgesic drug, inevitably causes injury. When it is overused, hypochlorous acid (HClO) is excessively generated due to metabolic abnormalities, resulting in the accumulation of HClO in the mitochondria of liver and kidney tissues and causing damage. In this study, we designed a series of HClO responsive ratiometric chemdosimeter NRH-X (NRH-O, NRH-S, and NRH-C) to evaluate liver and kidney injury, and found that NRH-O has a specific sensitive response to HClO. NRH-O can not only monitor the variations of endogenous HClO content of living cells by fluorescence ratio changes in the mitochondria but also detect the upregulation of HClO induced by APAP. In addition, NRH-O can also be used for anatomic diagnosis of liver and kidney injury by fluorescence ratio imaging of HClO in the tissues of inflammatory mice.

摘要

药物毒性引起的肝、肾损伤对人类健康构成严重威胁。对乙酰氨基酚(APAP)作为一种常用的解热镇痛药,不可避免地会造成损伤。当过量使用时,由于代谢异常会过度产生次氯酸(HClO),导致 HClO 在肝、肾组织的线粒体中积累,造成损伤。在本研究中,我们设计了一系列 HClO 响应的比率型化学传感器 NRH-X(NRH-O、NRH-S 和 NRH-C)来评估肝、肾损伤,发现 NRH-O 对 HClO 具有特异性敏感响应。NRH-O 不仅可以通过线粒体中荧光比率变化来监测活细胞内源性 HClO 含量的变化,还可以检测 APAP 诱导的 HClO 上调。此外,NRH-O 还可以通过炎症小鼠组织中 HClO 的荧光比率成像进行肝、肾损伤的解剖诊断。

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