Learning Objective
Explain the mechanisms, causes, and consequences of free radical injury, and describe how cells detoxify free radicals.
Free Radical Injury
Free radicals are highly reactive molecules with unpaired electrons. They damage cells through:
- Membrane lipid peroxidation → loss of membrane integrity
- Protein modification → enzyme inactivation, misfolding
- DNA strand breaks → mutations, apoptosis, or cancer
How Free Radicals Are Generated
Major sources include:
- Radiation (e.g., cancer therapy)
- Drug metabolism (Phase I reactions)
- Redox reactions (normal cellular metabolism)
- Nitric oxide (inflammation)
- Transition metals
- Iron and copper generate free radicals through the Fenton reaction
- Oxidative burst from neutrophils and macrophages
Activity
How Free Radicals Are Neutralized
Cells eliminate free radicals through:
- Scavenging enzymes
- Catalase
- Superoxide dismutase
- Glutathione peroxidase
- Antioxidants (vitamins A, C, E)
- Metal-binding proteins
- Transferrin (iron)
- Ceruloplasmin (copper)
- Spontaneous decay
Clinical Examples of Free Radical Injury
- Oxygen toxicity
- Retinopathy of prematurity (abnormal neovascularization)
- Bronchopulmonary dysplasia
- Reperfusion injury after thrombolysis
- Drug/chemical toxicity
- Acetaminophen overdose → hepatotoxicity
- Carbon tetrachloride (CCl₄) → converted to CCl₃ radical → fatty liver + centrilobular necrosis
- Metal overload diseases
- Hemochromatosis (iron)
- Wilson disease (copper)
