IC-MAC: A novel NIR fluorescent probe for monitoring the glutathione fluctuations in drug-induced liver injury

Drug-induced liver injury (DILI) is widely recognized as a major threat to global public health, posing significant obstacles to clinical treatment and drug innovation. The core mechanism underlying DILI progression is the depletion of intracellular glutathione (GSH), which is widely regarded as a key marker of oxidative liver injury and an important biomarker for early-stage DILI. In this study, we developed IC-MAC , a novel near-infrared (NIR) fluorescent probe for the highly sensitive and selective detection of GSH, which exhibited excellent photostability, a large Stokes Shift, and a significant fluorescence enhancement upon reaction with GSH. The probe demonstrated high biocompatibility and enabled real-time imaging of intracellular GSH fluctuations under physiological and oxidative stress conditions. In a mice model of acetaminophen-induced DILI, IC-MAC enabled dynamic visualization of GSH depletion in the liver and its recovery following therapeutic intervention. Fluorescence intensity was significantly correlated with the degree of GSH depletion and treatment response, providing robust evidence for the quantitative assessment of liver injury severity and drug efficacy. Collectively, these findings highlighted the potential of IC-MAC as a powerful platform for early DILI diagnosis and in vivo redox monitoring.