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

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 (O₂˙^-) selectively activates a near-infrared fluorescence (NIRF) output by generating fluorophore LW-OH. The C[double bond, length as m-dash]C linker of this hemicyanine fluorophore is subsequently oxidized by reactive nitrogen species (RNS) peroxynitrite (ONOO^-), resulting in cleavage to release xanthene derivative LW-XTD, detected using two-photon excitation fluorescence (TPEF). An alternative fluorescence pathway can occur through cleavage of LW-OTf by ONOO^- to non-fluorescent LW-XTD-OTf, which can react further with the second analyte O₂˙^- to produce the same LW-XTD fluorescent species. By combining NIRF and TPEF, LW-OTf is capable of differential and simultaneous detection of ROS and RNS in DILI using two optically orthogonal channels. Probe LW-OTf could be used to detect O₂˙^- or O₂˙^- 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 of tert-butylhydroxyanisole (BHA) against acetaminophen (APAP) toxicity in living HL-7702 cells. More importantly, TPEF and NIRF imaging confirmed an increase in levels of both O₂˙^- and ONOO^- in mouse livers during APAP-induced DILI (confirmed by hematoxylin and eosin (H&E) staining).

SUBMITTER: Wu L

PROVIDER: S-EPMC8179478 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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