Naphthalimide Fluorescent Skeleton for Facile and Accurate Quantification of Glutathione

Glutathione (GSH), the most prevalent nonprotein thiol in biological systems, acts as both an antioxidant to manipulate intracellular redox homeostasis and a nucleophile to detoxify xenobiotics. The fluctuation of GSH is closely related to the pathogenesis of diverse diseases. This work reports the construction of a nucleophilic aromatic substitution-type probe library based on the naphthalimide skeleton. After an initial evaluation, the compound R13 was identified as a highly efficient GSH fluorescent probe. Further studies demonstrate that R13 could readily quantify GSH in cells and tissues via a straightforward fluorometric assay with a comparable accuracy to the results from the HPLC. We then used R13 to quantify the content of GSH in mouse livers after X-ray irradiation, revealing that irradiation-induced oxidative stress leads to the increase of oxidized GSH (GSSG) and depletion of GSH. In addition, probe R13 was also applied to investigate the alteration of the GSH level in the Parkinson's mouse brains, showing a decrease of GSH and an increase of GSSG in Parkinson's mouse brains. The convenience of the probe in quantifying GSH in biological samples facilitates further understanding of the fluctuation of the GSH/GSSG ratio in diseases.

Automated summary

This study reports the construction of a probe library based on the naphthalimide skeleton to detect glutathione (GSH). Compound R13 was identified as a highly efficient GSH fluorescent probe and could be used to quantify GSH in cells and tissues. The probe was applied to study the alteration of GSH level in mouse livers after X-ray irradiation and Parkinson's mouse brains, providing valuable insights into the fluctuation of GSH/GSSG ratio in diseases.