2. • Provides key nutrients needed by the
body to neutralize free radicals.
• Helps protect against cellular damage.
May exhibit anti-aging benefits.
• Super ORAC (Primary) Antioxidants are
the body’s own natural defense against
free radicals.
• They scavenge or ‘mop’ them up before
they have a chance to harm cells.

3.  Slow or prevent damage to body cells
 May improve immune function and lower risk
for infection and cancer
 Carotenoids – beta carotene (familiar)
 Vitamin C
 Vitamin E
 Found in colorful fruits/veggies and grains

4. Free Radical Diseases
Alzheimer’s Stroke
Parkinson’s Photo-aging (wrinkles)
Macular Degeneration
& Cataracts Periodontitis
Emphysema
Lung Cancer
Coronary Heart Disease
Diabetes
Hypertension &
Alcohol &
Chronic Kidney Disease
Viral Liver Diseases
Prostate Cancer
Rheumatoid Arthritis
Colo-rectal Cancer
Peripheral Vascular Disease
Skin Cancer &
Osteoarthritis Melanoma

5. The free radical diseases
•Cancer initiation and promotion is
associated with chromosomal defects
and oncogene activation. It is possible
that endogenous free radical reactions,
like those initiated by ionizing radiation,
may result in tumour formation.

6. The free radical diseases
•Atherosclerosis may be due to free
radical reactions involving diet-derived
lipids in the arterial wall and serum to
yield peroxides and other substances.
These compounds induce endothelial
cell injury and produce changes in the
arterial walls .

7. Antioxidants
•vitamin E
•vitamin C
•carotenoids

8. vitamin E
•Vitamin E is a fat-soluble substance
present in all cellular membranes and is
mainly stored in adipose tissue, the liver
and muscle. Vitamin E is a principal
antioxidant in the body and protects
polyunsaturated fatty acids in cell
membranes from peroxidation.

9. Vitamin E and cancer
•Besides being a free radical scavenger,
vitamin E at high intakes enhances the
body's immune responses. Vitamin E also
inhibits the conversion of nitrites in the
stomach to nitrosamines, which are
cancer promoters.

10. Vitamin E and
cardiovascular disease
•Vitamin E intakes are associated with
lowered risk of angina and mortality from
heart disease.

11. Vitamin E and neurological
disorders
•Supplementation with vitamin C and
E might be of benefit in slowing the
progression of Parkinson's disease.

12. Vitamin C
•Vitamin C, or ascorbic acid, is a water-
soluble vitamin. This vitamin is a free
radical scavenger, it is considered to be
one of the most important antioxidants in
extra cellular fluids. Its protective effects
extend to cancer, coronary artery disease,
arthritis and aging.

13. Vitamin C and cancer
•Vitamin C is effective in protecting tissues
against oxidative damage. It suppresses the
formation of carcinogens. Numerous studies
have reported the protective effect of fruit and
vegetable consumption on incidence of
cancer . This is mainly attributed to the
protective effect of vitamin C against cancer.

14. Vitamin C and
cardiovascular disease
•Vitamin C may lower total cholesterol in
the blood, thus reducing the risk of
cardiovascular disease. Coronary heart
disease mortality is higher in those with
blood vitamin C levels that are near or in
the deficient range.

15. Vitamin C and cataracts
•High intake of fruits and vegetables
which are rich sources of ascorbic acid
appear to be protective too. In several
studies, cataract patients were shown to
have low vitamin C and E intakes and
low plasma vitamin C levels.

16. Carotenoids
•Carotenoids are a group of red, orange
and yellow pigments found in plant
foods, particularly fruits and vegetables.
• Some carotenoids like b-carotene act
as a precursor of vitamin A; others do
not.

17. Superoxide Dismutase (SOD) is
essential for the body and is:
A metalloprotein – containing several sub units
organised around a metallic group
And most importantly
An enzyme – the antioxidant enzyme SOD
eliminates, in a continuous way, superoxide
radicals, precursors of other oxygen reactive
forms (secondary free radicals)

18. SOD acts at the source. It is the first and one of the
major components of the body’s antioxidant system.
SOD is a powerful and efficient antioxidant:
• 1 iu SOD eliminates 1μmol superoxide/min and SOD has
an active lifespan of several days!
• In the end, billions of superoxide molecules destroyed
SOD is a primary antioxidant and
possibly our most important one

19. Reactive oxygen species:
formation of secondary free radicals
Hydroxyl radical induces the formation of
secondary free radicals:
• Secondary free radicals or organic peroxides
are very toxic
• They increase oxidative reactions which are
propagated from one to the next
• They are directly responsible for cell
alterations and destruction
• They indirectly participate in the inflammation
process

20. Pro-Oxidants Antioxidants
(Reactive Oxygen Species
Free Radicals)
OXIDATIVE STRESS
Cell & Tissue Damage
Oxidants Antioxidants
Cell / Tissue Damage Protection / Tissue Repair

21. Antioxidant systems:
the primary antioxidants
The primary antioxidants:
• are endogenous molecules
• act at the source (where free radicals are
created)
• are enzymes which continuously
eliminate the free radicals just formed:
- SOD eliminates the superoxide ion
- catalase and the glutathione peroxidase
eliminate hydrogen peroxide

22. Antioxidant systems:
the secondary antioxidants
The secondary antioxidants
• are exogenous molecules, carried by
food (vitamins A, C, E, polyphenols…)
• they scavenge the secondary free
radicals
• one molecule of a secondary antioxidant
traps one free radical molecule – a 1:1
relationship

23. Oxidants and antioxidants
in the body
Under normal circumstances and
conditions, the body’s endogenous
antioxidant systems are able to neutralize
the oxidant (free radical) molecules
Therefore
→ no oxidative stress means
→ no cell damage

24. Oxidative stress…
…is the result of an imbalance
between oxidant and antioxidant
production
increase of free radicals
→ antioxidant systems overpowered

25. Oxidative stress: consequences
A break in the equilibrium caused by…
• UVA and B
• Stress, overwork, diet
• Pollution, chemicals, cigarettes
• Chronic inflammation
… puts the body into oxidative stress:
→ attacks on cell constituents
(cell membranes, protein, lipids DNA)
Only solution: we must combat free radicals

26. 
Lipid L•
O2
(LH)
OH• H2O

Fe 2+

LOO•
H2O2
1
O2

UV light  
heme Fe H2O, H+
CoQ H +
O2 O2-• HOO•
 
NADPH H+
or CoQ
Figure 5. Pathways for the formation of reactive oxygen species
 Singlet oxygen  lipid radical
 Peroxyl radical  Haber-Weiss
 Superoxide reaction;  lipid peroxyl
radical anion  Superoxide  Fenton reaction radical
dismutase

27. The fight against
secondary free radicals…
…occurs with the secondary antioxidants
(vitamins A,C, E, polyphenols etc)
BUT
antioxidants (acting 1 against 1) are
quickly outnumbered and cannot
eliminate a continuous and strong
production of free radicals

28. Secondary antioxidants are vital
but just slow down the oxidative
stress
– we need to do something extra…

29. Functions of Pentose Phosphate Pathway
1) NADPH for biosynthetic pathways (e.g.,
synthesis of fatty acids and cholesterol);
2) NADPH for maintaining glutathione in its
reduced state .
3) Pentose sugar for synthesis of nucleic acids

30. Table 1. Reactive Oxygen Species
and Antioxidants that Reduce Them
Reactive Species Antioxidant
Singlet oxygen 1O2 Vitamin A, vitamin E
Superoxide radical (O2-•) superoxide dismutase, vitamin C
Hydrogen peroxide
(H2O2) Catalase; glutathione peroxidase
Peroxyl radical (ROO•) Vitamin C, vitamin E
Lipid peroxyl radical
Vitamin E
(LOO•)
Hydroxyl radical (OH•) Vitamin C

31. H2O2 glutathione 2 H2O
peroxidase
GSSG
2 glutathione
GSH reductase
NADP+
NADPH + H+
pentose pathway
Figure 6. Reactions of glutathione reduction and oxidation

32. SUMMARY OF ANTI-OXIDANT ENZYMES
Glutathione peroxidase: 2 GSH + H2O2  GSSG + 2 H2O
Uses selenium as a cofactor
Catalase : 2 H2O2  H2O + O2
Lipid Peroxidase: removes LOOH
Superoxide dismutase: 2 O2-• + 2H+ → H2O2 + O2
Mitochondrial - Mn2+ cofactor
Cytoplasmic – Cu2+-Zn2+ cofactors; mutations
associated with familial amyotrophic lateral sclerosis
(FALS)

33. NUTRITIONAL CORRELATE: SELENIUM
 selenocysteine in glutathione peroxidase
 intake may be related to lower cancer mortality
• cancer patients have lower plasma Se levels
• risk may be higher in those with low Se intake
• AZCC study – reduced incidence of prostate,
colon, lung cancers
 toxicity (> 1 mg/day) results in hair loss, GI upset,
nerve damage

34. lipid peroxyl radical Figure 7. Antioxidant cascade
LOO• rxn 5 LOOH Reduced forms/reduction
Oxidized forms/oxidation
Vit Ered VIT Eox
rxn 6 hydroxyl radical (OH•)
superoxide radical (O2-•)
rxn 9
VIT Cox Vit Cred
rxn 7 reduced rxn 4
products
H2O2
+ROOH Glutathioneox
Glutathionered
rxn 2 (GSSG) 2H2O
(GSH)
NADP+ rxn 1
NADPH + H+
Pentose phosphate pathway (rxn 8)
Glucose-6-P Ribulose-5-P

35. Medical Scenario:
If the antioxidant protective system in the red
blood cell becomes defective, hemolytic
anemia occurs; that is red blood cells undergo
hemolysis and their concentration in the blood
decreases. Such is the case if g luc o s e 6 -
p ho s p ha te d e hy d ro g e na s e is defective in the
pentose phosphate pathway. In individuals
whose glucose 6-phosphate dehydrogenase is
defective, there is insufficient NADPH produced
in red blood cells to maintain the ratio of
reduced glutathione to oxidized glutathione at
its normal value of well over 100. Hence,