Fluorescent probe for the imaging of superoxide and peroxynitrite during drug-induced liver injury

Luling Wu, Jihong Liu, Xue Tian, Robin R. Groleau, Steven D. Bull, Ping Li, Bo Tang, Tony D. James

Research output: Contribution to journalArticlepeer-review

97 Citations (SciVal)

Abstract

Drug-induced liver injury (DILI) is an important cause of potentially fatal liver disease. Herein, we report the development of a molecular probe (LW-OTf) for the detection and imaging of two biomarkers involved in DILI. Initially, primary reactive oxygen species (ROS) superoxide (O 2˙ ) selectively activates a near-infrared fluorescence (NIRF) output by generating fluorophoreLW-OH. The C-C linker of this hemicyanine fluorophore is subsequently oxidized by reactive nitrogen species (RNS) peroxynitrite (ONOO ), resulting in cleavage to release xanthene derivativeLW-XTD, detected using two-photon excitation fluorescence (TPEF). An alternative fluorescence pathway can occur through cleavage ofLW-OTfby ONOO to non-fluorescentLW-XTD-OTf, which can react further with the second analyte O 2˙ to produce the sameLW-XTDfluorescent species. By combining NIRF and TPEF,LW-OTfis capable of differential and simultaneous detection of ROS and RNS in DILI using two optically orthogonal channels. ProbeLW-OTfcould be used to detect O 2˙ or O 2˙ and ONOO in lysosomes stimulated by 2-methoxyestradiol (2-ME) or 2-ME and SIN-1 respectively. In addition, we were able to monitor the chemoprotective effects oftert-butylhydroxyanisole (BHA) against acetaminophen (APAP) toxicity in living HL-7702 cells. More importantly, TPEF and NIRF imaging confirmed an increase in levels of both O 2˙ and ONOO in mouse livers during APAP-induced DILI (confirmed by hematoxylin and eosin (H&E) staining).

Original languageEnglish
Pages (from-to)3921-3928
Number of pages8
JournalChemical Science
Volume12
Issue number11
Early online date4 Jan 2021
DOIs
Publication statusPublished - 21 Mar 2021

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