Simultaneous detection of mitochondrial viscosity and peroxynitrite in livers from subjects with drug-induced fatty liver disease using a novel fluorescent probe

Abstract

Drug-induced fatty liver disease (DIFLD) is a basic clinicopathological example of drug-induced liver injury (DILI). Some drugs can inhibit β-oxidation in hepatocyte mitochondria, leading to steatosis in the liver. Additionally, drug-induced inhibition of β-oxidation and the electron transport chain (ETC) can lead to increased production of reactive oxygen species (ROS) such as peroxynitrite (ONOO^-). Therefore, it is reasonable to suspect that compared to a healthy liver, viscosity and ONOO^- levels are elevated in livers during DIFLD. A novel, smart, dual-response fluorescent probe-Mito-VO-was designed and synthesized for the simultaneous detection of viscosity and ONOO^- content. This probe had a large emission shift of 293 nm and was capable of monitoring the viscosity of, and the ONOO^- content in, cell and animal models alike, either individually or simultaneously. For the first time, Mito-VO was successfully used to demonstrate the elevated viscosity and the amount of ONOO^- in livers from mice with DIFLD.

Keywords: Drug-induced fatty liver disease; Dual responsive; Fluorescent probe; Peroxynitrite; Viscosity.