Abstract
Over the past few decades, drug-induced liver damage (DILI) has become a serious public health problem due to drug abuse. Among multifarious reactive oxygen species, mounting evidence attests that ClO- has been used as a potential biomarker in DILI. In this work, a new "turn-on" fluorescent probe 1 was designed and synthesized by modifying 4'-hydroxybiphenyl-4-carbonitrile (dye 2) with N, N-dimethylthiocarbamate as a response site for detecting ClO-. Probe 1 displayed a low detection limit (72 nM), fast response time (30 s), wide pH operating range (6-8), great tissue penetration, large Stokes shift (125 nm) and 291-fold fluorescence enhancement at 475 nm in the mapping of ClO-. Probe 1 could trace amounts of exogenous and endogenous ClO- with high sensitivity in MCF-7 cells and HeLa cells. Expectantly, the fluoxetine-induced liver injury model is successfully established, and probe 1 has been used for detecting the fluctuation of ClO- levels in the mouse model of fluoxetine-induced liver injury. All in all, probe 1 with its high specificity, good biological compatibility and liver tissue penetration ability is expected to assist with the early diagnosis of DILI and the clinical screening of various new drugs. We expect that probe 1 could be efficiently used as a powerful molecular tool to predict clinical DILI and explore molecular mechanisms between molecules and disease.
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