Contents General properties Pathological damages FR Free radicals and cancer Free radicals and aging Drugs, foods, environment and free

radicals Latest research

Other Sources Chemotherapeutic agents Doxorubicin, Cyclophosphamide, 5-fluorouracil, Methotrexate Vincristine

Cancer Carcinogens Chemotherapy Radiation Latest techniques Prevention

Cancer

Chemotherapy Post-translational modifications (PTM) Protein oxidation Protein phosphorylation ER stress Calcium release Apoptosis ROS

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

Vitamin A Carotenoids and cancer

risk Strongest b-carotene Cervix, lung and oral

cavity Dietary antioxidants :

stomach and breast cancer

….Vitamin A Communication Growth regulating

signals from adjoining normal cells

Tumor growth suppressed

Vitamin C Vitamin C : 1) hyaluronidase

inhibitor system; 2) nitrosamines in

the GIT 3) cytochrome P-

450 system Selenium

aerodigestive system

Hypertension & FRs

Nitric oxide Antioxidants Glutathione Glutathione-depleted

rats Vitamin E and C to the

rats' diet

Hypertension AICR 400 and 800

gm per day Vitamins C, E, and b-

carotene reduce : Coronary events, Reperfusion injury, Platelet aggregation, LDL oxidation

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

Diabetes & FRs Type 1 diabetes ß-cell destruction cytokines RNS ROS Ferritin Fenton reaction Low levels of antioxidant genes

Diabetes and FRs

EUK-8 synthetic salen-manganese compounds

Catalytic superoxide dismutase,

Peroxidase, Catalase activity Inactivate superoxide and

nitrogen oxides

EUK-8 EUK-8 to mice with

established autoimmunity EUK-8 treatment and

survival of islet allografts in newly diabetic mice

Down Syndrome Excess SO levels

accumulation Antioxidant cellular

function

Cell Types

Cell type-specific responses to

H2O2 responses RPE Corneal fibroblasts

Neurological Disorders

Antioxidants slow the progression of certain neurological disorders

Oxidation disorders of the nervous system.

Vitamin C and E Parkinson's disease

Alzheimer Beta-amyloid and oxidative

toxicity, Oxidative damage to

neurons, Increases interneuronal

calcium levels, damage due to free radicals.

Carnosin

Treatment Vitamin E preventing

or alleviating neurological disorders,

Long-term Vitamin E deficiency progressive neurological syndrome

Melatonin Free radical

scavenger and antioxidant

Pineal gland, molecular damage

Melatonin lowers tissue damage and dysfunction

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

Cataract Oxidation, ultraviolet light, Damage to the proteins of

the lens. The oxidized protein

precipitates out and causes cloudiness of the lens.

….Cataract Antioxidants and antioxidant

enzymes, remove the damaged portion, but the oxidation occurs at a faster rate

With time, the damage becomes irreversible

Maculopathy Exposure to light, blue light, Age-related macular

degeneration Vitamin E Carotenoids are said to

decrease the risk of this disorder

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,

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

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.

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.

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

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.

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.

Cisplatin ROS, hydroxyl radicals, Cisplatin nephropathy Edarabone

Bibliography

NCBI pubmed Ignata connect Science daily Grays cancer institution American institution for cancer

research Univ. Florida Life extension magazine Net sources

www.mahmoodi.org