Reactive oxygen species and peroxynitrite (ROS/ONOO-)

Reactive oxygen species (ROS) and peroxynitrite are highly reactive molecules that play dual roles in biological systems, acting as both essential signaling molecules and mediators of cellular damage [1][2]. ROS, such as superoxide and hydrogen peroxide, are primarily generated by the mitochondrial respiratory chain and enzymes like NADPH oxidases, while peroxynitrite is a potent oxidant formed by the rapid reaction of superoxide with nitric oxide [1]. Under physiological conditions, these species regulate processes like cell proliferation, differentiation, and the immune response [2]. However, an imbalance between their production and the body's antioxidant defenses leads to oxidative and nitrosative stress, which causes irreversible damage to DNA, lipids, and proteins [3]. This damage is a critical driver in the pathogenesis of chronic conditions, including cardiovascular diseases, neurodegenerative disorders like Alzheimer's, and various cancers [1][3]. Therapeutic interventions targeting these species include direct scavengers, such as edaravone and N-acetylcysteine, as well as catalytic mimetics of endogenous enzymes like superoxide dismutase [3]. Despite their potential, clinical success has been limited by the challenge of selectively neutralizing harmful levels of ROS/peroxynitrite without disrupting vital physiological signaling pathways [2][3]. Sources: [1] Pacher, P., et al. (2007) Physiological Reviews; [2] Sies, H., et al. (2017) Annual Review of Biochemistry; [3] Forman, H. J., & Zhang, H. (2021) Nature Reviews Drug Discovery.

Other names

ROSReactive nitrogen speciesRNSFree radicalsOxidative stress mediatorsSuperoxideHydrogen peroxideHydroxyl radicalNitrosative stress mediators

Drugs targeting these species primarily function as chemical scavengers that directly neutralize reactive intermediates or as catalytic mimetics of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, to facilitate their conversion into stable, non-toxic molecules like water and oxygen [1][3].