General pathology · Cell injury, adaptation and death
Oxidative stress and free-radical injury !
- Mechanism
Free radicals are unstable molecules that steal electrons. When the body makes more than it can neutralize, they damage fats, proteins and DNA.
Updated 2026-11-01
What it is
A free radical has an unpaired electron, which makes it very reactive and able to start chain reactions. Cells make reactive oxygen species normally in mitochondria and in phagocytes. Oxidative stress appears when production outruns the defences (enzymes such as superoxide dismutase, catalase and glutathione peroxidase, plus antioxidant vitamins). It is a key mechanism in reperfusion injury, toxic injury, iron overload, radiation, inflammation and aging.
Key facts
- Nitric oxide can react with superoxide to form peroxynitrite, another damaging oxidant.
- Neutrophils use the oxidative burst on purpose: NADPH oxidase and myeloperoxidase make bleach-like hypochlorous acid to kill microbes.
- In chronic granulomatous disease, NADPH oxidase is missing and catalase-positive organisms survive.
- In G6PD deficiency red cells lack NADPH to keep glutathione reduced, so oxidant drugs or fava beans cause hemolysis.
- Lipofuscin, the brown pigment of aging, is made of lipid peroxidation products.
Step by step
- Sources: electron leak in the respiratory chain, radiation splitting water, phagocyte NADPH oxidase, drug metabolism and free iron or copper.
- Superoxide forms first and superoxide dismutase turns it into hydrogen peroxide.
- Catalase or glutathione peroxidase normally removes hydrogen peroxide.
- If iron is free, the Fenton reaction makes the hydroxyl radical instead.
- Radicals peroxidize membrane lipids in a chain reaction and oxidize proteins and DNA.
- Membranes leak, enzymes fail and DNA breaks: the cell dies by necrosis or apoptosis, or ages faster.
Clinical notes
- High oxygen exposure in premature newborns contributes to retinopathy of prematurity and bronchopulmonary dysplasia.
- Paraquat poisoning generates free radicals in the lung and leads to severe fibrosis.
Test yourself
Think of the answer, then tap the question to see it.
Which free radical is the most reactive and how does iron help form it?
The hydroxyl radical; ferrous iron converts hydrogen peroxide into hydroxyl radicals in the Fenton reaction.
Which three enzymes protect the cell against reactive oxygen species?
Superoxide dismutase, catalase and glutathione peroxidase.
Why does acetylcysteine protect the liver after an acetaminophen overdose?
It replenishes glutathione, which binds and neutralizes the toxic metabolite NAPQI before it damages hepatocytes.
Related
- Mechanisms of cell injury: ATP, mitochondria, calcium, membranes and DNA
- Hypoxia, ischemia and reperfusion injury
- Chemical (toxic) cell injury: direct and after metabolism
- Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon
- Cellular aging: telomeres, DNA damage, senescence and proteostasis
- Other forms of cell death: necroptosis, pyroptosis, ferroptosis
Related conditions
- Acetaminophen toxicity
- Hereditary hemochromatosis
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Chronic granulomatous disease
- Myocardial Infarction (Heart Attack)
- Retinopathy of prematurity
- Bronchopulmonary dysplasia
- Paraquat poisoning
- Wilson disease
- Iron poisoning
Elsewhere in DurgiPedia
- Reactive oxygen species and antioxidants
- Glutathione (GSH)
- Superoxide dismutase (SOD)
- Catalase
- Glutathione peroxidase (GPX)
- Vitamin E (α-tocopherol)
- Vitamin C (ascorbic acid)
- Glucose-6-phosphate dehydrogenase (G6PD)
- Phagocytosis and the respiratory burst
In Pharmacology
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hemochromatosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Acetaminophen overdose: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2024); Antioxidants: MedlinePlus (MedlinePlus, US National Library of Medicine, 2024).
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Representative model, for educational purposes only.