Development of a novel cytoplasmic hydroxyl radical-targeting antioxidant (TA293) that suppresses cellular senescence, inflammation, and apoptosis

Hydroxyl radicals ( • OH) exhibit the strongest oxidation potential of any reactive oxygen species (ROS) and react non-specifically with cellular components, such as nucleic acids, lipids and proteins. While mitochondrial • OH incites oxidative damage resulting in mitochondrial dysfunction, the actions of cytoplasmic • OH remain unknown as no cytoplasmic • OH-specific scavenger has been identified to date. To solve this problem, we developed the cytoplasm- and mitochondrion-specific • OH-targeted scavengers TA293 and mitoTA293, respectively. As expected, TA293 and mitoTA293 scavenged • OH, but not O 2 – or H 2 O 2 . Notably, TA293 scavenged pyocyanin-induced cytoplasmic • OH, but not mitochondrial radicals induced by antimycin A. Conversely, mitoTA293 scavenged • OH only in the mitochondria in vivo and in vitro . Interestingly, we found that cytoplasmic • OH plays a central role in cytoplasm ROS-induced oxidative stress, which potentiates cellular senescence, inflammation, and apoptosis in the kidney and lung. Based on these findings, we believe that TA293 could be a novel tool to study the effects of • OH damage within the cytoplasm.