free radicals
TRANSCRIPT
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Contents General properties Pathological damages FR Free radicals and cancer Free radicals and aging Drugs, foods, environment and free
radicals Latest research
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Other Sources Chemotherapeutic agents Doxorubicin, Cyclophosphamide, 5-fluorouracil, Methotrexate Vincristine
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Cancer Carcinogens Chemotherapy Radiation Latest techniques Prevention
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Cancer
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Chemotherapy Post-translational modifications (PTM) Protein oxidation Protein phosphorylation ER stress Calcium release Apoptosis ROS
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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
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Vitamin A Carotenoids and cancer
risk Strongest b-carotene Cervix, lung and oral
cavity Dietary antioxidants :
stomach and breast cancer
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….Vitamin A Communication Growth regulating
signals from adjoining normal cells
Tumor growth suppressed
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Vitamin C Vitamin C : 1) hyaluronidase
inhibitor system; 2) nitrosamines in
the GIT 3) cytochrome P-
450 system Selenium
aerodigestive system
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Hypertension & FRs
Nitric oxide Antioxidants Glutathione Glutathione-depleted
rats Vitamin E and C to the
rats' diet
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Hypertension AICR 400 and 800
gm per day Vitamins C, E, and b-
carotene reduce : Coronary events, Reperfusion injury, Platelet aggregation, LDL oxidation
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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
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Diabetes & FRs Type 1 diabetes ß-cell destruction cytokines RNS ROS Ferritin Fenton reaction Low levels of antioxidant genes
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Diabetes and FRs
EUK-8 synthetic salen-manganese compounds
Catalytic superoxide dismutase,
Peroxidase, Catalase activity Inactivate superoxide and
nitrogen oxides
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EUK-8 EUK-8 to mice with
established autoimmunity EUK-8 treatment and
survival of islet allografts in newly diabetic mice
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Down Syndrome Excess SO levels
accumulation Antioxidant cellular
function
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Cell Types
Cell type-specific responses to
H2O2 responses RPE Corneal fibroblasts
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Neurological Disorders
Antioxidants slow the progression of certain neurological disorders
Oxidation disorders of the nervous system.
Vitamin C and E Parkinson's disease
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Alzheimer Beta-amyloid and oxidative
toxicity, Oxidative damage to
neurons, Increases interneuronal
calcium levels, damage due to free radicals.
Carnosin
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Treatment Vitamin E preventing
or alleviating neurological disorders,
Long-term Vitamin E deficiency progressive neurological syndrome
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Melatonin Free radical
scavenger and antioxidant
Pineal gland, molecular damage
Melatonin lowers tissue damage and dysfunction
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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
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Cataract Oxidation, ultraviolet light, Damage to the proteins of
the lens. The oxidized protein
precipitates out and causes cloudiness of the lens.
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….Cataract Antioxidants and antioxidant
enzymes, remove the damaged portion, but the oxidation occurs at a faster rate
With time, the damage becomes irreversible
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Maculopathy Exposure to light, blue light, Age-related macular
degeneration Vitamin E Carotenoids are said to
decrease the risk of this disorder
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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,
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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
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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.
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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.
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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
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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.
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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.
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Cisplatin ROS, hydroxyl radicals, Cisplatin nephropathy Edarabone
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Bibliography
NCBI pubmed Ignata connect Science daily Grays cancer institution American institution for cancer
research Univ. Florida Life extension magazine Net sources
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www.mahmoodi.org