HClO imaging in vivo and drug-damaged liver tissues by a large Stokes shift fluorescent probe

Abstract

Drug-induced liver injury (DILI), as a classic acute inflammation, has attracted widespread concern due to its unpredictability and severity. Among the various reactive oxygen species, HClO has been used as a marker for the detection of DILI process. Thus, we designed and synthesized a "turn-on" fluorescent probe FBC-DS by modifying 3'-formyl-4'-hydroxy-[1,1'-biphenyl]-4-carbonitrile (FBC-OH) with N, N-dimethylthiocarbamate group for sensitively sensing HClO. Probe FBC-DS showed a low detection limit (65 nM), fast response time (30 s), an enormous Stokes shift (183 nm) and 85-fold fluorescence enhancement at 508 nm in the detection of HClO. Probe FBC-DS could monitor exogenous and endogenous HClO in living HeLa cells, HepG2 cells and zebrafish. In addition, probe FBC-DS has been successfully utilized in biological vectors for imaging acetaminophen (APAP)-induced endogenous HClO. Moreover, DILI caused by APAP is evaluated by probe FBC-DS through imaging over-expression of endogenous HClO in the mice liver injury models. All in all, we have every reason to believe that probe FBC-DS can be a potential tool to study the complex biological relationship between HClO and drug-induced liver injury.

Keywords: Cell imaging; Fluorescent probe; Hypochlorous acid; Large Stokes shift; Paracetamol.