Reactive electrophilic metabolites and reactive oxygen species (REM/ROS)

Reactive electrophilic metabolites (REMs) and reactive oxygen species (ROS) are highly reactive chemical entities that play dual roles in physiology and pathology. REMs are typically formed during the metabolic activation of drugs or xenobiotics, often by Cytochrome P450 enzymes, and can covalently bind to cellular nucleophiles such as DNA and proteins, leading to toxicity or mutagenicity (e.g., NAPQI from paracetamol) [PubMed: 15128291]. ROS, including superoxide and hydrogen peroxide, are byproducts of mitochondrial respiration or enzymatic activity and are essential for cell signaling at low concentrations; however, excessive production leads to oxidative stress [NIH/NIEHS]. This stress causes damage to lipids, proteins, and nucleic acids, contributing to the pathogenesis of cancer, neurodegenerative disorders like Alzheimer's, and cardiovascular diseases [StatPearls]. Therapeutic interventions include the use of antioxidants or scavengers like N-acetylcysteine to neutralize these species or the activation of the Nrf2 pathway to enhance endogenous antioxidant defenses [Nature Reviews Drug Discovery].

Other names

Electrophilic intermediatesOxidantsFree radicalsReactive speciesElectrophilesReactive nitrogen species

Neutralization of reactive species through chemical scavenging or induction of endogenous antioxidant enzymes.