Free Radicals

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Free Radicals

  1. 1. Contents  General properties  Pathological damages FR  Free radicals and cancer  Free radicals and aging  Drugs, foods, environment and free radicals  Latest research
  2. 2. Other Sources  Chemotherapeutic agents  Doxorubicin,  Cyclophosphamide,  5-fluorouracil,  Methotrexate  Vincristine
  3. 3. Cancer  Carcinogens  Chemotherapy  Radiation  Latest techniques  Prevention
  4. 4. Cancer 
  5. 5. Chemotherapy  Post-translational modifications (PTM)  Protein oxidation  Protein phosphorylation  ER stress  Calcium release  Apoptosis  ROS
  6. 6. Vitamin E  20 mg , 10 mg  Scavenger  Immune responses  Nitrites to nitrosamines  Oncogenes (H-ras and C-myc), and proliferation  50% oral cancer risk  Breast cancer risk
  7. 7. Vitamin A  Carotenoids and cancer risk  Strongest b-carotene  Cervix, lung and oral cavity  Dietary antioxidants : stomach and breast cancer
  8. 8. ….Vitamin A  Communication  Growth regulating signals from adjoining normal cells  Tumor growth suppressed
  9. 9. Vitamin C  Vitamin C :  1) hyaluronidase inhibitor system;  2) nitrosamines in the GIT  3) cytochrome P-450 system  Selenium aerodigestive system
  10. 10. Hypertension & FRs  Nitric oxide  Antioxidants  Glutathione  Glutathione- depleted rats  Vitamin E and C to the rats' diet
  11. 11. Hypertension  AICR 400 and 800 gm per day  Vitamins C, E, and b-carotene reduce :  Coronary events,  Reperfusion injury,  Platelet aggregation,  LDL oxidation
  12. 12. Drug Choices  Univ of Florida Medical School, statin with ACE inhibitor,  Decrease amounts of free radical  Oxidization of LDL  Endothelial cells  Chelating agents  Seresis Pharmaton
  13. 13. Diabetes & FRs  Type 1 diabetes  ß-cell destruction cytokines  RNS  ROS  Ferritin Fenton reaction  Low levels of antioxidant genes
  14. 14. Diabetes and FRs  EUK-8 synthetic salen- manganese compounds  Catalytic superoxide dismutase,  Peroxidase,  Catalase activity  Inactivate superoxide and nitrogen oxides
  15. 15. EUK-8  EUK-8 to mice with established autoimmunity  EUK-8 treatment and survival of islet allografts in newly diabetic mice
  16. 16. Down Syndrome  Excess SO levels accumulation  Antioxidant cellular function
  17. 17. Cell Types  Cell type-specific responses to  H2O2 responses  RPE  Corneal fibroblasts
  18. 18. Neurological Disorders  Antioxidants slow the progression of certain neurological disorders  Oxidation disorders of the nervous system.  Vitamin C and E Parkinson's disease
  19. 19. Alzheimer  Beta-amyloid and oxidative toxicity,  Oxidative damage to neurons,  Increases interneuronal calcium levels, damage due to free radicals.  Carnosin
  20. 20. Treatment  Vitamin E preventing or alleviating neurological disorders,  Long-term Vitamin E deficiency progressive neurological syndrome
  21. 21. Melatonin  Free radical scavenger and antioxidant  Pineal gland, molecular damage  Melatonin lowers tissue damage and dysfunction
  22. 22. Melatonin  Melatonin absorbed any route  Crosses all barriers,  Enter all parts of every cell  Preserves mitochondrial function,  low toxicity  Blood levels low, tissue levels higher, in bone marrow cells and bile
  23. 23. Cataract  Oxidation, ultraviolet light,  Damage to the proteins of the lens.  The oxidized protein precipitates out and causes cloudiness of the lens.
  24. 24. ….Cataract  Antioxidants and antioxidant enzymes, remove the damaged portion, but the oxidation occurs at a faster rate  With time, the damage becomes irreversible
  25. 25. Maculopathy  Exposure to light, blue light,  Age-related macular degeneration  Vitamin E  Carotenoids are said to decrease the risk of this disorder
  26. 26. Latest Uses  Polymer, in pig sperm, enhance the lifespan of human sperm in fertility treatments  Hybrid protein recognizes a molecule on the sperm's surface and the antioxidant vitamin E.  Pig sperm live longer than untreated cells,
  27. 27. Glutamate  Glutamate hippocampal cells of glutathione, incapable to reduce reactive oxygen species in cell death by oxidative stress.  cells resistant to glutamate increased phosphorylation of (CREB) and decreased ERK1/2
  28. 28. Glutamate  Increase in mRNA for receptors activated by the vasoactive intestinal peptide VIP and glutamate like the metabotropic glutamate receptor mGlu 1  Treating cells with VIP and glutamate led to the same changes in protein phosphorylation observed in resistant cells and induced the proto-oncogene Bcl-2.
  29. 29. Glutamate  Bcl-2 overexpression protected by increasing the amount of intracellular glutathione and Bcl- 2 knockdown by small interfering RNAs (siRNA) increased glutamate susceptibility of resistant cells.  Other receptors upregulated in this paradigm might represent useful targets in the treatment of neurological diseases associated with oxidative stress.
  30. 30. TBI and FRs  Overactivation of ERK secondary cell death mechanisms in TBI.  Fre radical scavenger S-PBN  Neuroprotective properties in TBI  Attenuates the early activation of ERK  Resulted in less activation of caspase-3  Subsequent DNA fragmentation  U0126 cortical atrophy at 2 weeks after trauma
  31. 31. Oxygenation therapy Disease is caused by absence of oxygen  "good energy" metabolism, detoxification, and immune system function  Oxygen therapies "good" energy, to "detoxify" metabolic poisons, and to kill invading organisms.
  32. 32. What's The Latest ?  ROS mtDNA UV human hepatoma cell  Alteres the ROS by MnSOD / catalase  Results accumulation of hydrogen peroxide oxidative damage to mtDNA of UV-irradiated cells, and overexpression of both MnSOD and catalase reduces the mtDNA damage and blocks the growth inhibition by UV.  Increased activity of MnSOD may lead to a toxic effect on mtDNA by UV- irradiation.
  33. 33. Cisplatin  ROS, hydroxyl radicals,  Cisplatin nephropathy  Edarabone
  34. 34. Bibliography  NCBI pubmed  Ignata connect  Science daily  Grays cancer institution  American institution for cancer research  Univ. Florida  Life extension magazine  Net sources
  35. 35. www.mahmoodi.org

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