Reversible NIR Ratiometric Probe for Monitoring Redox Homeostasis in Lipid Droplets during Ferroptosis-Driven Liver...

Area of Science:

• Biochemistry
• Cell Biology
• Medical Diagnostics

Background:

• Drug-induced liver injury (DILI) necessitates accurate diagnosis and prompt treatment to prevent severe liver damage.
• Cellular redox balance, particularly involving hypochlorous acid (HClO) and glutathione (GSH), is implicated in DILI pathogenesis.
• Lipid droplet (LD) dysfunction is increasingly recognized as a key factor in DILI and ferroptosis.

Purpose of the Study:

• To develop a novel fluorescent probe for dynamic monitoring of the HClO/GSH redox balance within lipid droplets.
• To investigate the role of redox imbalance in ferroptosis and DILI using the developed probe.
• To evaluate potential therapeutic interventions for DILI based on real-time redox monitoring.

Main Methods:

• Development of a near-infrared (NIR) ratio-fluorescent probe, PSeZ-ZD, with specific targeting for lipid droplets.
• Utilizing PSeZ-ZD for in situ imaging of HClO and GSH fluctuations in cellular models of DILI.
• Assessing the probe's performance in monitoring redox changes during ferroptosis and evaluating the efficacy of N-acetylcysteine (NAC) and silybin treatments.

Main Results:

• PSeZ-ZD demonstrated high sensitivity and specificity for detecting HClO (51.1 nM) and GSH (1.575 μM) with excellent reversibility.
• The probe successfully visualized dynamic HClO changes and LD targeting in live cells.
• In situ monitoring of HClO/GSH balance in acetaminophen (APAP)- and isoniazid (INH)-induced DILI models was achieved, with evaluated therapeutic responses.

Conclusions:

• The PSeZ-ZD probe is a valuable tool for real-time, in situ monitoring of redox status in lipid droplets during DILI.
• This technology offers new insights into the mechanisms of ferroptosis in DILI.
• The probe facilitates early DILI diagnosis and evaluation of therapeutic strategies.