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The Golgi apparatus is a crucial component of the endomembrane system and is involved in various physiological and pathological processes. Recently, increasing evidence shows that Golgi participates in oxidative stress in sepsis-induced acute lung injury (ALI). As a kind of reactive oxygen species (ROS), peroxynitrite (ONOO−) plays a significant role in a range of oxidative stress-related diseases. Therefore, accurately monitoring the level of ONOO− in the Golgi apparatus is crucial for revealing the mechanism of Golgi ONOO− in the sepsis-induced ALI. Unfortunately, no such probe has been reported to detect Golgi ONOO− in sepsis-induced ALI model. In this work, a Golgi-targetable probe FC-ONOO was designed and synthesized for high sensitivity and selectivity monitoring ONOO− generation during the Golgi stress response in sepsis-induced ALI model. The probe displayed high sensitivity (about 57 nM of detection limit) and good selectivity towards ONOO−. Additionally, it was successfully applied in mapping the increase of ONOO− levels in the Golgi of live cells induced by different stimuli. More importantly, the substantial increases in ONOO− levels in the Golgi apparatus were observed in the sepsis-induced ALI of mice for the first time. Given all its outstanding advantages, it has great potential for application in other ONOO− related diseases. [Display omitted] • A novel Golgi-targetable fluorescent probe for ONOO− was developed. • The probe displayed high sensitivity and good selectivity towards ONOO−. • The probe was successfully used to track Golgi ONOO− produced in live cells induced by different stimuli. • The probe was successfully applied to bioimaging Golgi ONOO− fluxes during sepsis-induced ALI for the first time. [ABSTRACT FROM AUTHOR]

Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO−) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO− holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI. We designed a probe DILI-ONOO based on the ICT mechanism for the purpose of measuring and visualizing ONOO− in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO− in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO− content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury. This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of DILI-ONOO shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI. [Display omitted] • A novel NIR probe DILI-ONOO for ONOO− of ferroptosis-mediated DILI was fabricated. • The probe DILI-ONOO displayed high selectivity and sensitivity toward ONOO−. • DILI-ONOO was used to image ONOO− in ferroptosis-mediated DILI model. • DILI-ONOO can achieve early identification of DILI prior to clinical methods. [ABSTRACT FROM AUTHOR]

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 inhibiting ferroptosis. Collectively, this work will provide a powerful guidance for the prophylaxis, diagnosis, and therapy of ferroptosis-mediated AKI. [Display omitted] • A novel near-infrared fluorescent probe NFP-ONOO for ONOO− was fabricated. • The probe NFP-ONOO displayed high selectivity and sensitivity toward ONOO−. • NFP-ONOO was used for imaging ONOO− in cells and zebrafish during ferroptosis. • NFP-ONOO was utilized to image ONOO− in ferroptosis-mediated AKI models. [ABSTRACT FROM AUTHOR]