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

Area of Science:

• Biochemistry
• Chemical Biology
• Molecular Biology

Background:

• Hydrogen polysulfides (H2Sn) are critical reactive sulfur species involved in cellular signaling, oxidative stress, and cell death.
• Real-time in vivo detection of H2Sn is essential for understanding its physiological roles but is challenging due to its instability.

Purpose of the Study:

• To develop and validate a near-infrared fluorescent (NIRF) probe for sensitive and specific detection of H2Sn in biological systems.
• To investigate the role of H2Sn in acute liver injury (ALI) models and its potential as a biomarker for injury severity.

Main Methods:

• Screening and characterization of a novel NIRF probe, DCICl-H2Sn, based on a dicyanoisophorone scaffold.
• Utilizing the probe for real-time monitoring of exogenous and endogenous H2Sn levels in live cells and mouse models of ALI.
• Assessing the correlation between H2Sn levels and liver injury severity induced by acetaminophen (APAP) or carbon tetrachloride (CCl4).

Main Results:

• The DCICl-H2Sn probe exhibited a 'turn-on' fluorescence response at 675 nm upon reaction with H2Sn, demonstrating high specificity and excellent photophysical properties.
• In vivo studies showed a negative correlation between H2Sn levels and the severity of APAP or CCl4-induced ALI.
• Administration of silybin (SLB) reduced liver injury and concurrently increased H2Sn levels.

Conclusions:

• The DCICl-H2Sn probe is an effective tool for real-time detection and dynamic monitoring of H2Sn in vitro and in vivo.
• H2Sn levels may serve as a potential biomarker for assessing the severity of acute liver injury.
• The findings highlight the protective role of H2Sn in liver injury and provide insights into its molecular mechanisms.