In situ observation of mitochondrial viscosity in liver of mice with drug-induced liver injury by near-infrared fluorescence imaging

Abstract

Drug-induced liver injury (DILI) has emerged as among of the undesirable drug effects, posing significant threats to human health. However, in clinical practice, there remains a shortage of dependable and pre-diagnosis tools for DILI. Numerous studies indicated that the elevated intrahepatic viscosity levels were closely linked to the onset and progression of DILI. Therefore, establishing reliable tools to monitor mitochondrial viscosity are crucial for prompt diagnosis of DILI in situ. Herein, we proposed a new near-infrared (NIR) fluorescence probe (Wyry-M-V) for detecting mitochondrial viscosity, in which consisted of xanthene, multiple viscosity-responsive rotors (diphenyl, vinyl cyanide, and benzyl chloride) and mitochondrial targeting site (pyridinium cation). Furthermore, the Wyry-M-V was triumphantly utilized in mitochondrial viscosity imaging upon treatment with lipopolysaccharide, nystatin and acetaminophen (APAP). Notably, based on the advantages of NIR emission wavelength, the Wyry-M-V was resoundingly used for the detection of mitochondrial viscosity in APAP-induced DILI mice model.

Keywords: DILI; In vivo imaging; Mitochondria; Near-infrared; Viscosity.