High-Selectivity Fluorescent Reporter toward Peroxynitrite in a Coexisting Nonalcoholic Fatty Liver and Drug-Induced Liver Diseases Model

Abstract

Peroxynitrite (ONOO^-), a highly reactive species, is profoundly involved in many physiological and pathological processes. Change of the ONOO^- level usually indicates an abnormal body function. Thus, it is desired to develop a highly reliable ONOO^- assay to elucidate its roles in a related disease environment. In this work, we have constructed a ratiometric molecule fluorescent probe <b>RTFP</b> toward ONOO^- with high specificity by the combination strategy of probe screening and a rational design method. <b>RTFP</b> displayed excellent detection sensitivity (detection limit: 4.1 nM) and produced a highly ratiometric emission signal (130-fold). Leveraging this probe, we showed the change of ONOO^- content in the free-fatty-acid-induced nonalcoholic fatty liver disease (NAFLD) and acetaminophen-induced drug-induced liver injury (DILI) cellular model and <i>for the first time</i> disclosed the involved mechanism of cytochrome P450 2E1 (CYP2E1) enzyme in NAFLD with a DILI pathological environment. Furthermore, <b>RTFP</b> also was utilized to visualize ONOO^- fluctuation of living liver tissues in a high-fat-diet-caused NAFLD model. We expected that this probe may help the study of liver injury in the exploration of mechanism and signal path.