Expansion
Reactive oxygen species damage lipids, proteins and DNA unless neutralised
Expansion
Sources of reactive oxygen species: normal mitochondrial respiration, the neutrophil respiratory burst, radiation, drug metabolism, transition metals via the Fenton reaction, and reperfusion of ischaemic tissue.
Damage: lipid peroxidation of membranes, protein oxidation and cross-linking, and DNA strand breaks and mutation.
Defences
- Enzymatic: superoxide dismutase, catalase, glutathione peroxidase
- Non-enzymatic: glutathione, vitamins C and E, beta-carotene, uric acid, caeruloplasmin and transferrin (by sequestering metals)
Clinical illustrations:
- Paracetamol overdose: the toxic metabolite NAPQI is normally conjugated by glutathione; once stores fall below about 30 per cent it binds hepatocyte proteins. N-acetylcysteine works by replenishing glutathione
- Reperfusion injury: restoring flow to ischaemic tissue generates a burst of radicals, which is why reperfusion itself causes damage in stroke and myocardial infarction
- Chronic granulomatous disease shows the beneficial side, since losing the ability to generate radicals causes recurrent infection
- Retinopathy of prematurity and bronchopulmonary dysplasia reflect oxygen toxicity