Reactive oxygen species and electrophilic metabolites (ROS/EM)

Reactive oxygen species (ROS) and electrophilic metabolites are highly reactive chemical entities produced during normal cellular metabolism or in response to environmental stressors. ROS include free radicals like superoxide and non-radicals like hydrogen peroxide, while electrophiles are electron-deficient species that can covalently modify cellular nucleophiles like DNA and proteins [1]. While they play essential roles in cell signaling and the immune response, an imbalance between their production and the body's antioxidant defenses leads to oxidative stress [2]. This state is a hallmark of numerous pathologies, including cancer, neurodegenerative diseases, and cardiovascular disorders, where ROS cause damage to lipids, proteins, and nucleic acids [3]. Therapeutic strategies often involve direct scavenging of these species or the activation of endogenous antioxidant pathways, such as the Nrf2-Keap1 system, to restore redox homeostasis [4]. However, the non-specific nature of these species and their dual role as signaling molecules present significant challenges for drug development [5]. Sources: [1] Sies, H., & Jones, D. P. (2020). Nature Reviews Molecular Cell Biology. [2] Halliwell, B., & Gutteridge, J. M. (2015). Free Radicals in Biology and Medicine. [3] Murphy, M. P., et al. (2022). Nature Metabolism. [4] Dinkova-Kostova, A. T., & Abramov, A. Y. (2015). Free Radical Biology and Medicine. [5] Forman, H. J., & Zhang, H. (2021). Nature Reviews Drug Discovery.

Other names

ROSReactive oxygen speciesElectrophilesFree radicalsOxidantsReactive nitrogen speciesRNSReactive metabolites

Drugs typically act by directly scavenging and neutralizing reactive species, providing precursors for endogenous antioxidants (e.g., glutathione), or by inducing the expression of antioxidant enzymes through the activation of the Nrf2 (Nuclear factor erythroid 2-related factor 2) signaling pathway [4, 5].