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

Hydrogen polysulfides (H2Sn), a key reactive sulfur species, play pivotal roles in cellular signaling, antioxidative stress, and cell death regulation. Revealing the dynamic changes of H2Sn levels in vivo is crucial for elucidating its physiological functions. However, real-time detection of H2Sn in vivo faces significant challenges due to its inherent instability. In this study, we screened a near-infrared fluorogenic (NIRF) probe DCICl-H2Sn for the detection of H2Sn in cells and mice models. This probe employed a dicyanoisophorone scaffold functionalized with ortho-NO2 substituted phenyl sulfonate groups, which endowed it with exceptional photophysical properties and high specificity toward H2Sn. Upon reaction with H2Sn, DCICl-H2Sn emitted a fluorescent "turn-on" signal at 675 nm. Benefiting from its excellent optical properties, DCICl-H2Sn enabled monitoring of both exogenous and endogenous H2Sn level changes in live cells. Leveraging DCICl-H2Sn, we explored the role of H2Sn in APAP or CCl4-induced acute liver injury (ALI) mice models. The results revealed a negative correlation between H2Sn levels and the severity of liver injury, suggesting that H2Sn 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 H2Sn levels. The present probe DCICl-H2Sn proved to be an effective tool for investigating the dynamic changes of H2Sn, which could help to uncover the molecular mechanisms of liver injury.