⚡ 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.
