Figure 2.

Reactive oxygen species (ROS) and ROS-generating and -scavenging enzymes. (a) ROS involved in ARDS. (b) The superoxide radical O₂⁻ is generated by the NADPH oxidase 2 (Nox2), the xanthine oxidase (XO), and the electron transfer chain (ETC) located in the mitochondria. O₂⁻ is dismutated to hydrogen peroxide (H₂O₂) by one of three superoxide dismutases (SODs), which are located in the cytosol (SOD1 ≙ CuZnSOD), in mitochondria (SOD2 ≙ MnSOD), or extracellularly, often associated with the extracellular matrix (SOD3 ≙ EC-SOD). One further source of H₂O₂ is Nox4, which is located in mitochondria or endoplasmic reticulum (ER) of endothelial as well as epithelial cells. H₂O₂ is the substrate for the myeloperoxidase-(MPO)-derived oxidant hypochlorous acid (HOCl⁻), known to cause tissue injury. Stored in neutrophil granules, MPO is released following neutrophil activation. In the Fenton reaction, H₂O₂ is further metabolized to the highly antimicrobial hydroxyl radical (˙OH). ROS-scavenging enzymes, such as catalase (CAT) or glutathione peroxidase (GPx), detoxify H₂O₂ to H₂O and O₂. To achieve this, GPx oxidizes GSH to GSSG, which in return is reduced via the glutathione reductase to GSH. Similarly, peroxiredoxin (Prx), belonging to a small family of peroxidases, reduces H₂O₂ by oxidizing thioredoxin (Trx), which then is restored to the reduced form by the thioredoxin reductase (not shown).