Molecular Optimization of a Near-Infrared Fluorogenic Probe for Hydrogen Polysulfide Imaging in Acute Liver Injury.

Hydrogen polysulfides (HS), a key reactive sulfur species, play pivotal roles in cellular signaling, antioxidative stress, and cell death regulation. Revealing the dynamic changes of HS levels is crucial for elucidating its physiological functions. However, real-time detection of HS faces significant challenges due to its inherent instability. In this study, we screened a near-infrared fluorogenic (NIRF) probe DCICl-HS for the detection of HS in cells and mice models. This probe employed a dicyanoisophorone scaffold functionalized with ortho-NO substituted phenyl sulfonate groups, which endowed it with exceptional photophysical properties and high specificity toward HS. Upon reaction with HS, DCICl-HS emitted a fluorescent "turn-on" signal at 675 nm. Benefiting from its excellent optical properties, DCICl-HS enabled monitoring of both exogenous and endogenous HS level changes in live cells. Leveraging DCICl-HS, we explored the role of HS in APAP or CCl-induced acute liver injury (ALI) mice models. The results revealed a negative correlation between HS levels and the severity of liver injury, suggesting that HS could be used as a potential biomarker for assessing the severity of ALI. Moreover, oral administration of silybin (SLB) significantly reduced liver injury and up-regulated HS levels. The present probe DCICl-HS proved to be an effective tool for investigating the dynamic changes of HS, which could help to uncover the molecular mechanisms of liver injury.