Peroxynitrite activated near-infrared fluorescent probe for evaluating ferroptosis-mediated acute kidney injury

Abstract

Ferroptosis is a form of programmed cell death mostly characterized by a serious misadjustment in the production and degradation of lipid reactive oxygen species (ROS). Meanwhile, numerous studies have indicated that ferroptosis is crucial to the progression and pathophysiology of acute kidney injury (AKI). ROS have been implicated as a pivotal causative factor in cell damage, peroxynitrite (ONOO−) is one of the most prominent ROS which is intimately correlated to ferroptosis-mediated AKI. Therefore, monitoring ONOO− levels in ferroptosis-mediated AKI is important for exploring its physiological and pathological roles. Nevertheless, no probes for detecting ONOO− in ferroptosis-mediated AKI have been reported. Meanwhile, resveratrol (Res) is a bioactive component and has been used to the treatment of AKI. However, the effect of Res on ferroptosis during AKI progression remains elusive. Herein, we evaluated the fluctuation of ONOO− during ferroptosis-mediated AKI using the near-infrared (NIR) fluorescence probe (NFP-ONOO) for the first time. The probe NFP-ONOO showed excellent specificity and sensitivity for the detection of ONOO−. Furthermore, utilizing this probe, we demonstrated Res effectively mitigates AKI induced by folic acid (FA) and cisplatin (CP) by inhibitingferroptosis. Collectively, this work will provide a powerful guidance for the prophylaxis, diagnosis, and therapy of ferroptosis-mediated AKI.