Diketopyrrolopyrrole-based sensor for over-expressed peroxynitrite in drug-induced hepatotoxicity via ratiometric fluorescence imaging
| Autor: | Jian Zhang, Jiamin Wang, Huihui Su, Jinying Liu, Xin Ji, Weili Zhao, Han Wang, Nannan Wang |
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| Rok vydání: | 2022 |
| Předmět: |
Liver injury
animal structures Chemistry Metals and Alloys Endogeny Glutathione Mitochondrion Condensed Matter Physics medicine.disease Surfaces Coatings and Films Electronic Optical and Magnetic Materials Acetaminophen chemistry.chemical_compound medicine.anatomical_structure Cytoplasm Lysosome Materials Chemistry medicine Biophysics Electrical and Electronic Engineering Instrumentation Peroxynitrite medicine.drug |
| Zdroj: | Sensors and Actuators B: Chemical. 352:130992 |
| ISSN: | 0925-4005 |
| Popis: | Early diagnosis and detection of drug-induced liver injury (DILI) is great significance for the effective prevention and treatment of patients with liver injury. Studies indicate that the up-regulation of peroxynitrite (ONOO ) levels in liver is profoundly involved in acetaminophen (APAP)-induced liver injury. Herein, we constructed diketopyrrolopyrrole (DPP)-based ratiometric fluorescent probes (DPP-DH-P and DPP-DEG-P) for detecting and imaging ONOO . Comparing two probes, DPP-DEG-P exhibited higher signal-to-noise ratio (2750-fold) and lower detection limit (3.5 nM) for tracking ONOO in solution. DPP-DH-P possessing better biocompatibility had been successfully applied to monitor the fluctuation of ONOO in LPS/IFN-γ or APAP-treated hepatocytes with a high signal-to-noise ratio (20-fold) by ratiometric imaging. Moreover, the probe was used to evaluate the repair effect of glutathione on DILI. We unexpectedly discovered that DPP-DH-P and DPP-DH targeted lysosomes and mitochondria, respectively. Based on the change of ONOO induced by APAP, we observed that DPP-DH-P and the generated DPP-DH diffused from lysosome into cytoplasm, and DPP-DH did not target mitochondria due to the effect of endogenous ONOO , these indirectly reflected the dysfunction of organelles. Observably, this work will accelerate a deeper comprehending for the pathogenesis of DILI, and furnish an effective tool for the diagnosis and treatment of DILI. |
| Databáze: | OpenAIRE |
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