A Fluorogenic ONOO<sup>–</sup>-Triggered Carbon Monoxide Donor for Mitigating Brain Ischemic Damage
Linfeng Xing, Bin Wang, Jin Li, Xinjian Guo, Xicun Lu, Xiaohua Chen, Haitao Sun, Zhenrong Sun, Xiao Luo, Suhua Qi, Xuhong Qian, Youjun Yang
Abstract
Ischemia–reperfusion (I/R) injuries are from the secondary radicals of ONOO–. Direct radical scavenging is difficult because of their high reactivity. ONOO– is longer-lived than the radicals in the biological milieu. Scavenging ONOO– suppresses radical generation preventively. CO is neuroprotective during ischemia. With the scaffold of carbon-caged xanthene, we designed an OONO–-triggered CO donor (PCOD585). Notably, PCOD585 exhibited a concomitant fluorescence turn-on upon ONOO–detection, facilitating microscopic monitoring. PCOD585 was cytoprotective in oxygen–glucose deprivation (OGD)-insulted PC-12 cells. It was permeable to the blood–brain barrier and further exhibited neuroprotective effects to MCAO rats by reducing infarction volume, cell apoptosis, and brain edema.