Dong Junming, Yang Yushun, Fan Xiangjun, Zhu Hai-Liang, Li Zhen
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Avenue, Nanjing, 210023, China.
Jinhua Advanced Research Institute, Jinhua, 321019, China.
Mater Today Bio. 2023 Jun 13;21:100689. doi: 10.1016/j.mtbio.2023.100689. eCollection 2023 Aug.
Herein, an activable fluorescent probe for peroxynitrite (ONOO), named , was constructed for the accurate imaging in the processes of formation and inhibition of drug-induced liver injury induced by Acetaminophen (APAP). During the in-solution tests on the general optical properties, the probe showed advantages including good stability, wide pH adaption, high specificity and sensitivity in the monitoring of ONOO. Subsequently, the probe was further applied in the model mice which used APAP to induce the injury and used inhibiting agents (GSH, Glu, NAC) to treat the induced injury. The construction of the liver injury model was confirmed by the pathological staining and the serum indexes including ALT, AST, ALP, TBIL as well as LDH. During the formation of the drug-induced liver injury, the fluorescence in the red channel enhanced in both time-dependent and dose-dependent manners. In inhibition tests, the inhibition of the liver injury exhibited the reduction of the fluorescence intensity. Therefore, could achieve the accurate imaging in the processes of formation and inhibition of drug-induced liver injury. The information here might be helpful for the early diagnosis and the screening of potent treating candidates in liver injury cases.
在此，构建了一种用于过氧亚硝酸盐（ONOO）的可激活荧光探针，名为 ，用于对乙酰氨基酚（APAP）诱导的药物性肝损伤形成和抑制过程进行精确成像。在溶液中对其一般光学性质进行测试时，该探针在监测ONOO方面表现出稳定性好、pH适应性广、特异性高和灵敏度高的优点。随后，该探针进一步应用于用APAP诱导损伤并用抑制剂（GSH、Glu、NAC）治疗诱导损伤的模型小鼠。通过病理染色以及包括ALT、AST、ALP、TBIL和LDH在内的血清指标证实了肝损伤模型的构建。在药物性肝损伤形成过程中，红色通道的荧光以时间和剂量依赖性方式增强。在抑制试验中，肝损伤的抑制表现为荧光强度降低。因此， 能够在药物性肝损伤的形成和抑制过程中实现精确成像。此处的信息可能有助于肝损伤病例的早期诊断和有效治疗候选药物的筛选。
