High Selectivity\nFluorescence and Electrochemical\nDual-Mode Detection of Glutathione in the Serum of Parkinson’s\nDisease Model Mice and Humans

Parkinson’s disease (PD) is\na progressive neurodegenerative\ndisorder characterized by the loss of dopaminergic neurons and the\naccumulation of alpha-synuclein. Glutathione (GSH), a key antioxidant,\nis significantly depleted in PD patients. This study presents a dual-mode\ndetection strategy for selectively determining GSH using a single\nprobe. A series of “turn-on” electrochemical and fluorescent\nprobes were developed, with resorufin (Re) serving as the reporting\nunit and featuring specific GSH recognition sites. Among these, the\n7-(3,5-dinitrophenoxy)-3<i>H</i>-phenoxazin-3-one (Re-DNP)\nprobe was selected for its high selectivity as both a fluorescent\nand electrochemical probe. Its response to GSH was superior in comparison\nto that observed for hydrogen sulfide (H<sub>2</sub>S) and cysteine\n(Cys). For electrochemical detection using screen-printed carbon electrode\n(SPCE)/carbon nanotube (CNT) modified electrodes, the detection limit\nfor GSH was 5 μM, with a linear range of 25–500 μM.\nIn fluorescence detection, the probe produced a 78-fold increase in\nemission at 630 nm in the presence of GSH, with a strong linear correlation\nbetween fluorescence intensity and GSH concentration in the range\nof 10–700 μM, and a detection limit of 2 μM. When\napplied to real clinical serum samples, the probe demonstrated significantly\nlower GSH levels in both PD mice and human patients compared to healthy\ncontrols. This dual-mode detection method provides a sensitive and\naccurate tool for GSH detection, with potential applications in understanding\nGSH’s role in PD and related neurodegenerative diseases.