Unveiling the Crucial Roles of O2•- and ATP in Hepatic Ischemia-Reperfusion Injury Using Dual-Color/Reversible Fluorescence Imaging

Jihong Liu, Wen Zhang, Xin Wang, Qi Ding, Chuanchen Wu, Wei Zhang, Luling Wu, Tony D. James, Ping Li, Bo Tang

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15 Citations (SciVal)


Hepatic ischemia-reperfusion injury (HIRI) is mainly responsible for morbidity or death due to graft rejection after liver transplantation. During HIRI, superoxide anion (O2•-) and adenosine-5'-triphosphate (ATP) have been identified as pivotal biomarkers associated with oxidative stress and energy metabolism, respectively. However, how the temporal and spatial fluctuations of O2•- and ATP coordinate changes in HIRI and particularly how they synergistically regulate each other in the pathological mechanism of HIRI remains unclear. Herein, we rationally designed and successfully synthesized a dual-color and dual-reversible molecular fluorescent probe (UDP) for dynamic and simultaneous visualization of O2•- and ATP in real-time, and uncovered their interrelationship and synergy in HIRI. UDP featured excellent sensitivity, selectivity, and reversibility in response to O2•- and ATP, which rendered UDP suitable for detecting O2•- and ATP and generating independent responses in the blue and red fluorescence channels without spectral crosstalk. Notably, in situ imaging with UDP revealed for the first time synchronous O2•- bursts and ATP depletion in hepatocytes and mouse livers during the process of HIRI. Surprisingly, a slight increase in ATP was observed during reperfusion. More importantly, intracellular O2•-─succinate dehydrogenase (SDH)─mitochondrial (Mito) reduced nicotinamide adenine dinucleotide (NADH)─Mito ATP─intracellular ATP cascade signaling pathway in the HIRI process was unveiled which illustrated the correlation between O2•- and ATP for the first time. This research confirms the potential of UDP for the dynamic monitoring of HIRI and provides a clear illustration of HIRI pathogenesis.

Original languageEnglish
Pages (from-to)19662-19675
Number of pages14
JournalJournal of the American Chemical Society
Issue number36
Early online date1 Sept 2023
Publication statusPublished - 13 Sept 2023

Bibliographical note

This work was supported by the National Natural Science Foundation of China (22134004, 21927811, 22074083, and 22077075), the Key Research and Development Program of Shandong Province (2018YFJH0502), the National Science Foundation of Shandong Province of China (ZR2020ZD17), and the Local Science and Technology Development Fund Guided by the Central Government of Shandong Province (YDZX2022012). L.W. wishes to thank the University of Bath for supporting his work in the UK. T.D.J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01) for support.

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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