Peroxynitrite activatable double spiral ring derived fluorescent probe for imaging of inflammation and drug-induced liver injury

Abstract

As a high reactive oxygen species, peroxynitrite (ONOO−) has been correlated to a wide variety of pathologies, including inflammation and drug-induced liver injury. Imaging peroxynitrite variation in real time in the process of inflammation and DILI would provide a powerful way to study the progression and prognosis of diseases. Herein we present two unique structures with hybrid skeleton of fluorescein (FLSP) or rhodamine (Rhod-SP) and spirobenzopyran possessing two closed double spiro-ring. Peroxynitrite-induced oxidative ring opening restores the fluorescence of the probe and enables the fluorescence enhancement detection of ONOO−. FLSP exhibits a superior selectivity and sensitivity to ONOO− with 22.5-folds increment and insensitive to other reactive oxygens. It can be successfully applied to detection of endogenous and exogenous ONOO− in living cells and zebrafish and confirmed the activate CYP450-mediated ONOO− production in the process of APAP induced DILI. In addition, using the FLSP, we reveal the upregulation of ONOO− in the inflammatory sites and damaged liver through in vivo imaging. Concordance of results for in vivo imaging and HE staining confirm the remediation with UDCA, NAC and GSH in vivo. These results revealed that FLSP has great potential in early diagnosis of DILI and provides a new approach to drug screening.