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

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.