Visualizing GSH-ONOO^- Redox and Tracking Lesion-Remedy of Acute Kidney Oxidative Injury Based on a Dual-Site Chemosensor.

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^-: λ_ex = 410 nm, λ_em = 548 nm; GSH: λ_ex = 490 nm, λ_em = 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.