期刊
ANALYTICAL CHEMISTRY
卷 93, 期 16, 页码 6551-6558出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c00742
关键词
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资金
- National Natural Science Foundation of China [21535004, 91753111, 21405097, 21390411, 21475079]
- Technological Special Project for Significant New Drugs Development [2017ZX09301030004]
- Key Research and Development Program of Shandong Province [2018YFJH0502]
- Natural Science Foundation of Shandong Province [ZR2020MB067]
Drug-induced liver injury (DILI) is the most common reason for the post-marketing withdrawal of drugs. Research has identified a positive correlation between nitroxyl (HNO) levels in the Golgi apparatus and mitochondria and DILI, and uncovered the involvement of catalase in HNO synthesis.
Drug-induced liver injury (DILI) is the most common reason for the post-marketing withdrawal of drugs. Poor understanding of the mechanisms of DILI presents a large challenge in clinical diagnosis. Previous evidences indicate a potential relationship between reactive nitrogen species (RNS) and DILI. Hence, we developed two specific probes, Golgi-HNO and Mito-HNO, for the multicolored and simultaneous in situ imaging of nitroxyl (HNO) in the Golgi apparatus and mitochondria, respectively. We discovered a significant rise in HNO levels in the livers of mice with DILI, which means that for the first time, we revealed a positive correlation between HNO levels and DILI. Based on changes in the HNO level, we also successfully explored the extent of liver damage induced by an anticarcinogen, bleomycin. In addition, we uncovered catalase was involved in HNO synthesis, which is the unprecedented function of catalase. These findings demonstrate that HNO is an ideal biomarker for DILI diagnosis, and Golgi-HNO and Mito-HNO are ideal fluorescent probes to study in situ HNO changes in various physiological and biochemical processes.
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