Imaging of sulfhydryl fluctuations in mouse models of drug-induced liver injury via a novel near-infrared fluorescence probe

Abstract

Drug-induced liver injury (DILI), caused by pharmaceuticals or their metabolites, is closely associated with oxidative stress, and it is a serious public health concern. Sulfhydryl groups, due to their antioxidant and detoxification capabilities, play a pivotal role in mitigating oxidative stress-induced cellular damage in related diseases. Therefore, precise monitoring of intracellular sulfhydryl levels is essential for evaluating the severity and progression of such conditions. In this study, we synthesized a series of near-infrared fluorescent probes by incorporating the furan carbonyl group as a novel recognition moiety linked to the dicyanoisophorone structure. Following systematic screening, we identified NIR-Cl as the most effective probe, demonstrating high sensitivity and selectivity for sulfhydryl groups, as well as rapid responsiveness to concentration changes under physiological pH conditions. The application of NIR-Cl in a zebrafish model of oxidative stress and a mouse model of DILI revealed significant fluctuations in sulfhydryl levels, highlighting the probe’s capacity to monitor dynamic redox processes in vivo. These results offer important insights into the molecular mechanisms of DILI, positioning NIR-Cl as a promising tool for diagnosing and managing oxidative stress-related diseases. Furthermore, the study highlights the probe’s potential to advance redox biology research and support the development of targeted therapeutic strategies.