An innovative near-infrared fluorescent probe designed to track the evolution of carboxylesterase in drug-induced liver injury

Abstract

Drug-induced liver injury (DILI) is a common side effect of medicines, which is a pathological process of drug-induced liver dysfunction or injury. As an important enzyme mainly existing in the human liver, carboxylesterase (CE) has been proven that the decrease or lack of its activity is related to the occurrence and severity of DILI. Therefore, detecting the change of CE level in DILI will help to understand the pathological and physiological repercussions of DILI. In this study, we designed and synthesized a novel near-infrared (NIR) fluorescent probe (MB-CE) that displayed excellent optical properties for detecting CE. The probe MB-CE featured low cytotoxicity, high sensitivity, and selectivity. Furthermore, the MB-CE was successfully utilized to detect endogenous CE in a liver injury caused by acetaminophen (APAP) and its subsequent treatment with glutathione (GSH) in cells. Notably, with the assistance of probe MB-CE, we successfully achieved realized in situ monitoring of CE decreased in the APAP-induced liver injury mouse model. These results indicate the potential clinical utility of the probe MB-CE for investigating the occurrence, progression, and treatment of DILI.