Accurate imaging in the processes of formation and inhibition of drug-induced liver injury by an activable fluorescent probe for ONOO−

Abstract

Herein, an activable fluorescent probe for peroxynitrite (ONOO−), named NOP, 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, NOP 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.

Keywords

• Fluorescent probe
• Detection of peroxynitrite
• Drug-induced liver injury
• Accurate real-time imaging