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Published on: June 30, 2018
Dual-Colored Fluorescence Imaging of Mitochondrial HNO and Golgi-HNO in Mice with DILI
Hui Wang1, Cuifang Liu1, Zixu He1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.
Abstract:
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.
Insights
Reactive nitrogen species (RNS), specifically nitroxyl (HNO), are linked to drug-induced liver injury (DILI). New probes reveal elevated HNO levels in DILI, establishing HNO as a potential diagnostic biomarker.
Area of Science:
- Biochemistry
- Toxicology
- Medical Imaging
Background:
- Drug-induced liver injury (DILI) is a primary cause for drug withdrawal.
- The mechanisms underlying DILI remain poorly understood, complicating clinical diagnosis.
- Reactive nitrogen species (RNS) have been implicated in DILI pathogenesis.
Purpose of the Study:
- To investigate the role of nitroxyl (HNO), a type of RNS, in DILI.
- To develop novel fluorescent probes for simultaneous in situ imaging of HNO.
- To establish HNO as a potential biomarker for DILI diagnosis.
Main Methods:
- Development of Golgi-HNO and Mito-HNO fluorescent probes for in situ HNO detection.
- Multicolor imaging of HNO in the Golgi apparatus and mitochondria.
- Quantification of HNO levels in DILI mouse models.
Main Results:
- A significant increase in hepatic HNO levels was observed in DILI mouse models.
- A positive correlation between elevated HNO levels and DILI severity was established.
- The probes successfully monitored liver damage extent induced by bleomycin.
- Catalase was identified as a key enzyme in HNO synthesis, a novel function.
Conclusions:
- Nitroxyl (HNO) is a promising biomarker for diagnosing DILI.
- The developed Golgi-HNO and Mito-HNO probes are effective tools for studying in situ HNO dynamics.
- These findings offer new insights into DILI mechanisms and diagnostics.
