Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity  

作　　者：Nannan Wang Han Wang Jian Zhang Xin Ji Huihui Su Jinying Liu Jiamin Wang Weili Zhao 

机构地区：[1]Key Laboratory for Special Functional Materials of Ministry of Education,School of Materials Science and Engineering,Henan University,Kaifeng 475004,China [2]School of Pharmacy,Institutes of Integrative Medicine,Fudan University,Shanghai 201203,China [3]Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province,Henan University,Kaifeng 475004,China

出　　处：《Chinese Chemical Letters》2022年第3期1584-1588,共5页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (Nos. 82030107 and 21702046);the China Postdoctoral Science Foundation (No. 2018M632757);the Key Scientific and Technological Project of Henan Province (Nos.212102311064 and 212102310870);the Innovation Scientists and Technicians Troop Construction Projects of Henan Province(No. 20IRTSTHN020)。

摘　　要：Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.

关 键 词：Anti-tuberculosis drug induced liver injury PEROXYNITRITE Fluorescent probe Drug-induced liver injury BIOIMAGING 

分 类 号：O657.3[理学—分析化学] TQ460.72[理学—化学]