Article| August 26, 2026

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Reversible Imaging of the HOCl/GSH Redox Cycle Reveals the HOCl–Ferroptosis Regulatory Axis in Ischemic Stroke

Chuanhao Xu # ;

Zhirong Guan # ;

Rui Wang # ;

Haoyi Liang # ;

Yuxuan Chen;

Yang Yu;

Govindaraj Tamil Selvan;

Jiao Lu * ;

Fabiao Yu * ;

Kun Dou *

Anal. Chem. (2026)

https://doi.org/10.1021/acs.analchem.6c04276

Abstract

Ferroptosis has emerged as a significant contributor to ischemia–reperfusion injury after ischemic stroke; however, the redox events linking oxidative stress to ferroptotic injury remain poorly understood. To this end, we developed DX, a fluorescent probe targeting lipid droplets and capable of reversibly tracking the HOCl/GSH redox cycle in living systems. By incorporating a selenomorpholine-based redox switch into a rationally engineered BODIPY scaffold, DX achieves an on–off–on dynamic fluorescence response to oxidative and reductive stimuli. In oxygen–glucose deprivation/reperfusion cell models and mouse models of ischemic stroke, DX facilitated real-time detection of HOCl accumulation during reperfusion. Imaging results combined with transcriptomic and biochemical analyses revealed a close correlation between HOCl signaling and ferroptosis progression. Notably, inhibition of ferroptosis significantly reduced HOCl production in vivo and alleviated IS-induced tissue damage. These findings uncover the HOCl–ferroptosis regulatory axis in ischemic stroke and demonstrate the utility of reversible molecular imaging in studying redox-regulated cell death.

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