2. Contents
 General properties
 Pathological damages FR
 Free radicals and cancer
 Free radicals and aging
 Drugs, foods, environment and free
radicals
 Latest research

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

5. Cancer
 Carcinogens
 Chemotherapy
 Radiation
 Latest techniques
 Prevention

6. Cancer


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

11. 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

12. Vitamin A
 Carotenoids and
cancer risk
 Strongest b-carotene
 Cervix, lung and oral
cavity
 Dietary antioxidants :
stomach and breast
cancer

13. ….Vitamin A
 Communication
 Growth regulating
signals from
adjoining normal
cells
 Tumor growth
suppressed

14. Vitamin C
 Vitamin C :
 1) hyaluronidase
inhibitor system;
 2) nitrosamines in
the GIT
 3) cytochrome
P-450 system
 Selenium
aerodigestive
system

16. Hypertension & FRs
 Nitric oxide
 Antioxidants
 Glutathione
 Glutathione-
depleted rats
 Vitamin E and C to
the rats' diet

17. Hypertension
 AICR 400 and 800
gm per day
 Vitamins C, E, and
b-carotene reduce :
 Coronary events,
 Reperfusion injury,
 Platelet
aggregation,
 LDL oxidation

18. 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

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

21. Diabetes and FRs
 EUK-8 synthetic salen-
manganese compounds
 Catalytic superoxide
dismutase,
 Peroxidase,
 Catalase activity
 Inactivate superoxide and
nitrogen oxides

22. EUK-8
 EUK-8 to mice with
established
autoimmunity
 EUK-8 treatment and
survival of islet
allografts in newly
diabetic mice

23. Down Syndrome
 Excess SO levels
accumulation
 Antioxidant
cellular function

24. Cell Types
 Cell type-specific
responses to
 H2O2 responses
 RPE
 Corneal fibroblasts

25. Neurological
Disorders
 Antioxidants slow the
progression of certain
neurological disorders
 Oxidation disorders of the
nervous system.
 Vitamin C and E
Parkinson's disease

27. Alzheimer
 Beta-amyloid and
oxidative toxicity,
 Oxidative damage to
neurons,
 Increases interneuronal
calcium levels, damage
due to free radicals.
 Carnosin

28. Treatment
 Vitamin E
preventing or
alleviating
neurological
disorders,
 Long-term Vitamin
E deficiency
progressive
neurological
syndrome

29. Melatonin
 Free radical
scavenger and
antioxidant
 Pineal gland,
molecular
damage
 Melatonin lowers
tissue damage
and dysfunction

30. 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

32. Cataract
 Oxidation, ultraviolet light,
 Damage to the proteins of
the lens.
 The oxidized protein
precipitates out and
causes cloudiness of the
lens.

33. ….Cataract
 Antioxidants and
antioxidant enzymes,
remove the damaged
portion, but the oxidation
occurs at a faster rate
 With time, the damage
becomes irreversible

35. Maculopathy
 Exposure to light, blue light,
 Age-related macular
degeneration
 Vitamin E
 Carotenoids are said to
decrease the risk of this
disorder

36. 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,

39. 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

40. 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.

41. 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.

42. 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

43. 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.

44. 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.

45. Cisplatin
 ROS, hydroxyl radicals,
 Cisplatin nephropathy
 Edarabone

46. Bibliography
 NCBI pubmed
 Ignata connect
 Science daily
 Grays cancer institution
 American institution for cancer
research
 Univ. Florida
 Life extension magazine
 Net sources

47. www.mahmoodi.org