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.
摘要：
药物性肝损伤（DILI），作为典型的急性炎症，由于其不可预测性和严重性，引起了广泛关注。在各种活性氧中，HClO已被用作检测DILI过程的标记。因此，我们通过用N修饰3'-甲酰-4'-羟基-[1,1'-联苯]-4-甲腈（FBC-OH），设计并合成了“开启”荧光探针FBC-DS，N-二甲基硫代氨基甲酸酯基团用于敏感地感应HClO。FBC-DS探针显示低检测限(65nM),快速响应时间（30秒），在检测HClO时，会产生巨大的斯托克斯位移（183nm）和508nm处的85倍荧光增强。FBC-DS探针可以监测HeLa细胞中外源性和内源性HClO，HepG2细胞和斑马鱼。此外,FBC-DS探针已成功用于对乙酰氨基酚（APAP）诱导的内源性HClO成像的生物载体中。此外，通过探针FBC-DS通过对小鼠肝损伤模型中内源性HClO的过表达进行成像来评估由APAP引起的DILI。总而言之，我们完全有理由相信FBC-DS探针可以成为研究HClO与药物性肝损伤之间复杂生物学关系的潜在工具。
