Reactive oxygen species and electrophilic cytotoxic intermediates (ROS/ECI)

Reactive oxygen species (ROS) and electrophilic cytotoxic intermediates are highly reactive chemical entities produced during normal cellular metabolism or as a result of drug biotransformation (NCI, 2023). While ROS play roles in cell signaling at low levels, their accumulation leads to oxidative stress, causing irreversible damage to DNA, proteins, and lipids in normal tissues (Betteridge, 2000). Electrophilic intermediates, often generated by Cytochrome P450 enzymes, can covalently bind to cellular macromolecules, leading to organ toxicity such as hepatotoxicity or nephrotoxicity (Liebler, 2008). Therapeutic intervention focuses on the use of cytoprotective agents that scavenge these reactive species or bolster endogenous antioxidant defenses to mitigate the side effects of cytotoxic drugs, particularly in oncology (Hensley et al., 2009). For example, Mesna is used to neutralize acrolein, an electrophilic metabolite of cyclophosphamide, to prevent hemorrhagic cystitis (Monach et al., 2010). Managing these species is a critical strategy for improving the safety profile of high-dose chemotherapy and radiation (Sies, 2015).

Other names

ROSReactive oxygen speciesElectrophilic metabolitesOxidative stress mediatorsReactive electrophilesCytotoxic intermediates

Chemical scavenging, covalent binding to neutralize electrophiles, and enhancement of endogenous antioxidant capacity.