Glutathione and reactive oxygen species (GSH/ROS)

Glutathione (GSH) is a tripeptide (gamma-glutamyl-cysteinyl-glycine) that serves as the primary endogenous antioxidant in eukaryotic cells, playing a critical role in neutralizing reactive oxygen species (ROS) (PubChem, CID 124886; NIH, PMC4055602). ROS are chemically reactive molecules containing oxygen, such as superoxide and hydrogen peroxide, produced as byproducts of aerobic metabolism or environmental stress (StatPearls, NBK541064). The balance between GSH and ROS is vital for maintaining cellular redox homeostasis; an imbalance favoring ROS leads to oxidative stress, causing damage to lipids, proteins, and DNA (PubMed, 22649245). In therapeutic contexts, the GSH/ROS axis is targeted to either protect healthy cells from oxidative damage using precursors like N-acetylcysteine or to selectively induce ROS-mediated apoptosis in cancer cells via GSH-depleting agents like buthionine sulfoximine (PubMed, 28236006; Nature Reviews Drug Discovery, 10.1038/nrd.2017.244). This system is central to the pathophysiology of numerous conditions, including neurodegenerative diseases, cardiovascular disorders, and various cancers (PubMed, 24514233).

Other names

GSHRedox systemOxidative stress componentsThiol-based antioxidant systemL-gamma-glutamyl-L-cysteinyl-glycine

Drugs targeting this system work by scavenging free radicals, acting as substrates for enzymatic reduction of peroxides, conjugating with electrophiles for detoxification, or inhibiting glutathione synthesis to induce oxidative stress-mediated cell death (PubMed, 28236006; StatPearls, NBK541064).