Reactive oxygen and nitrogen species and electrophilic xenobiotics (RONS/Electrophiles)

Reactive oxygen and nitrogen species (RONS) and electrophilic xenobiotics are a broad class of highly reactive molecules that induce oxidative and electrophilic stress in biological systems (Sies, H., 2015, PMID: 25588755). RONS, including superoxide, hydroxyl radicals, and nitric oxide, are generated endogenously during mitochondrial respiration and immune activation, while electrophilic xenobiotics are exogenous compounds that react with cellular nucleophiles such as DNA and protein thiols (Halliwell & Gutteridge, 2015). At physiological levels, these species function as critical signaling molecules in processes like vasodilation and immune defense; however, their overproduction leads to damage of lipids, proteins, and nucleic acids (Forman et al., 2014, PMID: 24561250). This damage is a hallmark of various pathologies, including cancer, neurodegenerative disorders, and chronic inflammation. Pharmacological intervention typically focuses on neutralizing these species using direct scavengers (antioxidants) or indirectly by activating the Nrf2-Keap1 pathway to upregulate endogenous detoxification enzymes (Zhang, D.D., 2010, PMID: 20478357).

Other names

Reactive Oxygen Species (ROS)Reactive Nitrogen Species (RNS)OxidantsElectrophilic StressorsPro-oxidantsFree Radicals

Drugs targeting these species generally act through three primary mechanisms: 1) Direct scavenging or neutralization of free radicals and oxidants (e.g., Vitamin C, Edaravone); 2) Induction of the endogenous antioxidant response, primarily via the activation of the Transcription Factor Nrf2, which leads to the expression of phase II detoxification enzymes (e.g., Dimethyl fumarate); and 3) Inhibition of the enzymatic sources of RONS, such as NADPH oxidase or Xanthine oxidase (He et al., 2020, PMID: 32206158).