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Visualizing GSH-ONOO- Redox and Tracking Lesion-Remedy of Acute Kidney Oxidative Injury Based on a Dual-Site
Meili Yang1,2, Zuzhe Kang2, Xinpei Zhong2
1Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China.
Abstract:
Drug-induced acute kidney injury (DIAKI) is strongly associated with the accumulation of peroxynitrite (ONOO-) and the depletion of glutathione (GSH), both of which contribute to increased morbidity and mortality. Owing to the lack of an effective method for the real-time monitoring of nephrotoxicity, it remains a diagnostic and therapeutic challenge and is considered a significant issue in clinical practice. Herein, a dual-site fluorescent chemosensor, BPS is developed, which enables the simultaneous real-time monitoring of ONOO- and GSH through distinct channels (ONOO-: λex = 410 nm, λem = 548 nm; GSH: λex = 490 nm, λem = 660 nm) without spectral crosstalk. The sensor displays remarkable sensitivity toward ONOO- and GSH, with low detection limits (181 nm and 2.42 µm, respectively), exceptional specificity, and anti-interference effects. BPS is used to monitor ONOO-/GSH in real time to track the lesion of cisplatin-stimulated DIAKI and the following remedy process in mice and HK-2 cells for the first time. BPS provides a feasible tool for investigating oxidative stress-related DIAKI disease processes and further exploring some physiological mechanisms. Moreover, this study also offers a strategy for visualizing, modulating, and controlling the intracellular GSH/ONOO- redox.
Insights
A new fluorescent sensor, BPS, enables real-time monitoring of peroxynitrite (ONOO-) and glutathione (GSH) to track drug-induced acute kidney injury (DIAKI) and its treatment. This tool aids in understanding oxidative stress in kidney disease.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Toxicology
Background:
- Drug-induced acute kidney injury (DIAKI) is a critical clinical issue linked to peroxynitrite (ONOO-) accumulation and glutathione (GSH) depletion.
- Current diagnostic and therapeutic strategies for DIAKI are challenged by the lack of effective real-time nephrotoxicity monitoring methods.
- Oxidative stress plays a significant role in the pathogenesis of DIAKI, highlighting the need for tools to track key redox species.
Purpose of the Study:
- To develop a novel dual-site fluorescent chemosensor (BPS) for simultaneous, real-time monitoring of ONOO- and GSH.
- To investigate the potential of BPS in tracking the progression and treatment of cisplatin-induced DIAKI in cellular and animal models.
- To provide a new strategy for visualizing and modulating intracellular redox balance in the context of kidney injury.
Main Methods:
- Development of a dual-site fluorescent chemosensor, BPS, with distinct excitation and emission channels for ONOO- and GSH.
- Characterization of BPS for sensitivity, specificity, and anti-interference capabilities against ONOO- and GSH.
- Application of BPS for in vivo and in vitro monitoring of ONOO-/GSH levels during cisplatin-induced DIAKI and subsequent treatment in mice and HK-2 cells.
Main Results:
- The BPS sensor successfully achieved simultaneous real-time monitoring of ONOO- and GSH without spectral crosstalk.
- BPS demonstrated high sensitivity (181 nM for ONOO-, 2.42 µM for GSH), specificity, and anti-interference properties.
- Real-time tracking of ONOO-/GSH dynamics in cisplatin-induced DIAKI models confirmed the sensor's utility in disease progression and remedy monitoring.
Conclusions:
- The developed BPS chemosensor offers a feasible tool for investigating oxidative stress-related DIAKI disease processes.
- BPS enables real-time visualization and modulation of intracellular GSH/ONOO- redox balance, advancing our understanding of kidney injury mechanisms.
- This study presents a novel strategy for monitoring and potentially managing redox imbalances in DIAKI and related conditions.
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