Oxidative Stress
Oxidative stress is a state in which the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) exceeds the capacity of antioxidant defenses. In the context of this vault, it is the primary driver of HSA structural damage in chronic liver disease.
Key ROS/RNS species
- H₂O₂ (hydrogen peroxide)
- HOCl (hypochlorous acid — from neutrophil MPO)
- ONOO⁻ (peroxynitrite — from NO + superoxide)
- ·OH (hydroxyl radical — Fenton reaction with free Fe/Cu)
HSA as the primary plasma antioxidant
- Cys34 free thiol is the main extracellular antioxidant scavenger — see Oxidation
- N-terminal domain chelates Cu²⁺/Fe²⁺ → prevents Fenton reaction
- Under sustained oxidative stress: HMA → HNA1 (reversible) → HNA2 (irreversible)
Clinical relevance in this research
- Liver fibrosis: systemic oxidative stress from hepatic dysfunction → progressive Cys34 oxidation
- DILI: acute oxidative burst from drug reactive metabolites → early Cys34 modification (detected by SEB test at D3, before ALT/AST at D7)
- ACLF: HNA2 >12% predicts 30/90-day mortality — oettl-2013
- HNA1 acts as pro-inflammatory signal (p38 MAPK, cytokine storm) — alcaraz-quiles-2018
For detailed PTM mechanism and mass signatures, see Oxidation.