Understanding Free Radical Injury

The science of oxidative stress and cellular damage

General Pathology

Introduction to Free Radical Injury

Key Concept: Watch this video to understand the fundamental concepts of Free Radical Injury before diving into the interactive lessons.

What Are Free Radicals?

Free radicals are unstable molecules with unpaired electrons, making them highly reactive. Unlike stable molecules with paired electrons, free radicals desperately seek to pair with other electrons to become stable. This chemical instability makes them potentially harmful to the body.

Key Characteristics:

  • Contain one or more unpaired electrons
  • Highly reactive and unstable
  • Can initiate chain reactions
  • Produced during normal metabolism
  • Increased by environmental factors

Common Types:

  • Superoxide (O₂•⁻)
  • Hydroxyl radical (•OH)
  • Nitric oxide (•NO)
  • Peroxyl radical (ROO•)
  • Lipid peroxyl radical (LOO•)

Chain Reaction Example:

A•
+
B
A
+
B•

Free radical (A•) steals an electron from stable molecule (B), turning it into a new free radical (B•) that continues the chain reaction.

Cellular Damage Mechanisms

Lipid Peroxidation

Free radicals attack cell membranes (lipid bilayers), creating a chain reaction that damages membrane structure and function.

DNA Damage

Free radicals cause strand breaks and base modifications (like 8-hydroxyguanine), leading to mutations if not repaired.

Protein Damage

Oxidation changes protein structure, causing unfolding, loss of function, and potential cellular dysfunction.

Oxidative Stress:

Occurs when free radical production overwhelms the body's antioxidant defenses, leading to cumulative cellular damage over time.

Disease Connections

Age-Related Diseases

  • Cardiovascular: Oxidized LDL contributes to plaque formation
  • Neurodegenerative: Alzheimer's, Parkinson's linked to brain oxidative stress
  • Cataracts: Lens protein oxidation causes clouding
  • Diabetes: Beta cell damage impairs insulin production

Other Conditions

  • Cancer (DNA mutation accumulation)
  • Chronic inflammatory diseases (rheumatoid arthritis)
  • Male infertility (sperm oxidative damage)
  • Premature aging (cellular damage accumulation)

Inflammation Connection:

Free radicals and inflammation form a vicious cycle - inflammation produces free radicals which cause more tissue damage, leading to more inflammation.

Antioxidant Defenses

Enzymatic Antioxidants

  • Superoxide dismutase (SOD): Converts superoxide to hydrogen peroxide
  • Catalase: Breaks down hydrogen peroxide to water and oxygen
  • Glutathione peroxidase: Reduces lipid hydroperoxides and hydrogen peroxide

Non-Enzymatic Antioxidants

  • Vitamin C (water-soluble)
  • Vitamin E (lipid-soluble)
  • Glutathione (cellular antioxidant)
  • Carotenoids (beta-carotene, lycopene)
  • Polyphenols (flavonoids, resveratrol)

Neutralization Mechanism:

Antioxidants donate electrons to free radicals without becoming reactive themselves, effectively stopping the chain reaction of cellular damage.

Prevention Strategies

Dietary Recommendations

  • Eat 5+ servings of colorful fruits/vegetables daily
  • Include nuts, seeds, and whole grains
  • Choose foods rich in vitamins C, E, and polyphenols
  • Drink green tea and other antioxidant beverages
  • Limit processed foods and refined sugars

Lifestyle Factors

  • Avoid smoking and secondhand smoke
  • Limit alcohol consumption
  • Use sun protection (SPF 30+)
  • Exercise regularly (150+ min/week)
  • Practice stress management techniques

Exercise Paradox:

While intense exercise temporarily increases free radical production, regular exercise strengthens antioxidant defenses and makes cells more resistant to oxidative stress.