Fluorescence Dynamics Imaging Reveals Inflammation Driven by Ferroptosis through a MAO/ONOO- Dual-Responsive Probe.

Inflammation, as a critical defensive response of the body, can exacerbate tissue damage through oxidative cascade reactions when it becomes uncontrolled. Among the key oxidative stress mediators are monoamine oxidase A (MAO-A) and peroxynitrite (ONOO-), which synergistically promote cellular damage. To further elucidate their molecular mechanisms of action, precise and reliable imaging tools are required for spatiotemporal dynamic monitoring of both mediators. Addressing the limitations of traditional dual-probe detection, which suffers from inconsistencies in distribution and response, this study developed a mitochondria-targeted dual-responsive fluorescent probe, KMO, achieving the first in situ real-time visualization of MAO-A and ONOO- in inflammatory cells and an acute hepatitis mouse model. Utilizing this tool, we revealed a self-amplifying cycle in inflammation characterized by "MAO-A activation─ONOO- burst─ferroptosis─inflammation exacerbation", and demonstrated that inhibiting ferroptosis can disrupt this pathway. This work not only provides a fluorescent imaging tool but also establishes a theoretical and experimental foundation for elucidating the mechanisms of acute inflammation and targeted interventions.