Fig. 1

Basics of ROS. The formation of intracellular O ^⋅−₂ could be deemed as a result of the activity of NOXs, or oxidative phosphorylation in mitochondria. Superoxide molecule as a reductant or an oxidant lies at the hub of a series of redox reactions. Mostly, superoxide radicals are catalyzed to H₂O₂ by superoxide dismutases, including cytosolic SOD1, mitochondrial SOD2, and extracellular SOD3. Alternatively, superoxide reacts with NO^⋅ to form strong oxidative ONOO⁻, which can mediate oxidative modification of protein residues and induce RNS production. Physiological levels of H₂O₂ are strictly regulated by multiple mechanisms, such as acting with PRX, GPX, and CAT to form H₂O, while H₂O₂ is also able to oxidation cysteine residues on proteins for signaling transduction. If, however, excessive H₂O₂ is not controlled, it will be decomposed into OH^⋅ in the presence of metal cations (e.g., Fe²⁺ and Cu⁺). OH^⋅ can react with DNA and irreversibly damage DNA base units and also reacts with RH, forming R^⋅. R^⋅ further reacts with O₂, building up RO^⋅ or ROO^⋅, which can cause lipid peroxidation by a series of reaction steps and ultimately subvert membrane stability and permeabilization