| Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity |
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| 引用本文： | Nannan Wang,Han Wang,Jian Zhang,Xin Ji,Huihui Su,Jinying Liu,Jiamin Wang,Weili Zhao. Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity[J]. 中国化学快报, 2022, 33(3): 1584-1588. DOI: 10.1016/j.cclet.2021.09.046 |
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| 作者姓名： | Nannan Wang Han Wang Jian Zhang Xin Ji Huihui Su Jinying Liu Jiamin Wang Weili Zhao |
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| 作者单位： | 1. Key Laboratory for Special Functional Materials of Ministry of Education, School of Materials Science and Engineering, Henan University;2. School of Pharmacy, Institutes of Integrative Medicine, Fudan University;3. Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University |
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| 基金项目： | 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); |
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| 摘 要： | Pyrazinamide(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. Utili...
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| 收稿时间： | 2021-06-27 |
Endogenous peroxynitrite activated fluorescent probe for revealing anti‐tuberculosis drug induced hepatotoxicity |
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| Affiliation: | 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 |
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| Abstract: | Pyrazinamide (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. |
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