Makindo Medical Notes

⚡ Therapeutic trials of antioxidants (Vitamin C, Vitamin E, flavonoids, beta-carotene) have largely been disappointing — suggesting that simply supplementing does not fully overcome complex oxidative stress mechanisms. Free radicals are unstable molecules with unpaired electrons 🧪. They can trigger oxidative stress, damaging lipids, proteins, and DNA. Controlled in small amounts, they are useful in immunity and signalling — but in excess, they accelerate aging and disease.

🔑 Key Concepts

• Types:
  • 🧪 Reactive Oxygen Species (ROS): superoxide (O2•-), hydroxyl radical (•OH), hydrogen peroxide (H2O2).
  • 🧪 Reactive Nitrogen Species (RNS): nitric oxide (NO•), peroxynitrite (ONOO-).
• Sources:
  • Endogenous 🧬: mitochondria (ETC leakage), NADPH oxidase, xanthine oxidase, peroxisomes, immune cells (respiratory burst).
  • Exogenous 🌍: pollutants, smoking 🚬, radiation ☢️, drugs/chemicals.
• Oxidative Stress:
  • Occurs when ROS production > antioxidant defenses.
  • Leads to lipid peroxidation, protein denaturation, and DNA mutations.
• Antioxidants:
  • Endogenous 🧬: superoxide dismutase (SOD), catalase, glutathione peroxidase.
  • Exogenous 🌿: Vitamin C, Vitamin E, beta-carotene, polyphenols.

⚙️ Detailed Pathways

• ROS Formation:
  • O2•- (mitochondria) → detoxified by SOD → H2O2.
  • H2O2 → Fenton reaction → •OH (most destructive free radical 💥).
  • O2•- + NO• → ONOO- → damages proteins/lipids.
• Damage Mechanisms:
  • 🧱 Lipid peroxidation → membrane rupture, ↑ permeability.
  • ⚙️ Protein oxidation → enzyme inactivation, misfolding.
  • 📖 DNA damage → base modifications, strand breaks → mutations → cancer risk.
• Antioxidant Defenses:
  • Enzymatic: SOD, catalase, glutathione peroxidase.
  • Non-enzymatic: Vitamin C (aqueous), Vitamin E (lipid membranes), glutathione (universal scavenger).

🩺 Clinical Relevance

• 🔬 Cancer: oxidative DNA damage → mutations. Chronic inflammation fuels tumorigenesis.
• ❤️ Cardiovascular: ROS → endothelial dysfunction, LDL oxidation → atherosclerosis.
• 🧠 Neurodegeneration: Alzheimer’s, Parkinson’s, ALS linked to ROS-mediated neuronal death.
• ⏳ Aging: cumulative oxidative damage supports the “free radical theory of aging.”

📌 Quick Summary

⚡ Free radicals = unstable + reactive. 🧪 ROS (O2•-, •OH, H2O2), RNS (NO•, ONOO-). 🧬 Sources: mitochondria, immune burst, pollutants. 🛡️ Antioxidants: SOD, catalase, glutathione, Vitamins C & E. 🩺 Clinical: Cancer, CVD, neurodegeneration, aging.