1. ANTIOXIDANT
Narveer Shekhawat

2. We will discuss
 ROS : Definition, Source, function and effect on human
body
 Antioxidants: Definition, Type and Examples
 Different disorders where Antioxidants is indicated
 Role of ROS in these disorders
 Treatment options
 Antioxidant USPs

3. ROS - FREE RADICALS
DEFINITION
 Free radicals are molecules with an unpaired electron in their
outer atomic orbital, causing the molecule to be extremely reactive
 Free radicals cause oxidative damage in biological systems, which
includes damage to the cell membrane and other structures, DNA
molecules, lipids, and proteins
 This damage arises from exposure to free radicals

4. ROS - FREE RADICALS
SOURCE
1.Byproduct of cellular respiration
2. Synthesized by enzyme systems –
phagocytic cells, neutrophils and
macrophage
3. Exposure to ionizing radiation
4. Smoking, herbicides, pesticides, fried foods, etc

5. ROS - FREE RADICALS
FUNCTION
1. Necessary for production of some hormones (thyroxine).
2. Generated to kill some types of bacteria and engulfed pathogens.
3. Normal cell functions and cell signaling.
4. A balance:
a. Free radicals generated by normal processes do become harmful if
inadequate anti-oxidant defenses are present. A balance between
production and removal/inactivation is required.
b. When free radicals are present in excess of the defense mechanism’s
ability to control them is when damage may occur.
c. Anti-oxidants – compounds which will provide electrons to free
radicals to neutralize them. The compounds are able to accommodate

6. ROS - FREE RADICALS
EFFECT ON HUMAN
 Excessive ROS can induce oxidative damage in
cell constituents and promote a number of
degenerative diseases and aging.
 ROS have been implicated in more than 100
diseases

7. ROS IS IMPLICATED IN
 Diabetic complications
 CVD – Atherosclerosis
 Debility – Chronic fatigue
 Prostate cancer
 Infertility
 Pregnancy complications
 Breast Cancer
 Eye Disorders

8. HOW TO CONTROL ROS
 Free radicals are formed when an electron has
escaped from the outer orbit of molecule
 Free radicals quench electron from nearby cell and
inturn damage the cell
 Free radicals can be neutralized by donating an
electron and stabilizing the molecule

9. AN ANTIOXIDANT IS A MOLECULE
CAPABLE OF INHIBITING
THE OXIDATION OF OTHER
MOLECULES. OXIDATION IS
A CHEMICAL REACTION THAT
TRANSFERS ELECTRONS OR
HYDROGEN FROM A SUBSTANCE
TO AN OXIDIZING AGENT.
OXIDATION REACTIONS CAN
PRODUCE FREE RADICALS. IN
TURN, THESE RADICALS CAN
START CHAIN REACTIONS.

10. TYPES OF ANTIOXIDANTS:
 Mainly Hydrophilic and Hydrophobic
Antioxidant enzymes:
1. Catalase
2. Glutathione peroxidase
3. Glutathione reductase
4. Super oxide dismutase (both Cu-Zn and Mn)
Metals binding proteins:
1. Ceruloplasmin
2. Ferritin
3. Lactoferrin
4. Metallotheinein
5. Transferrin
6. Hemoglobin
7. Myoglobin

11. Common antioxidants (scavengers)
1. Bilirubin
2. Carotenoids
a. Beta-carotene b. Alpha-carotene
c. Beta-cryptoxanthin d. Lutein
e. Zeaxanthin f. Lycopene
3. Flavonoids
a. Quercetin
b. Rutin
c. Catechin
4. Uric acids 5. Thiols (R-SH)
6. Coenzyme Q10 7. Vitamin A, C, E, D.
Others antioxidants
1. Copper 2. glutathione (GSH)
3. Alpha lipoic acid 4.Manganise
5. Selenium 6. Zinc

12. Antioxidant compounds
Foods containing high levels
of these antioxidants
Vitamin C (ascorbic acid) Fresh Fruits and vegetables
Vitamin E (tocopherols,
tocotrienols)
Vegetable oils
Polyphenolic antioxidants
(resveratrol, flavonoids)
Tea, coffee, soy, fruit, olive
oil, chocolate, cinnamon, orega
no and red wine
Carotenoids(lycopene,
carotenes, lutein)
Fruit, vegetables and eggs.
Natural antioxidants

13. ANTIOXIDANT SYSTEM IN OUR BODY
Superoxide dismutase (SOD)
Catalase
Glutathione peroxidase
The enzymatic antioxidants
The nonenzymatic antioxidants
Vitamins E, C, A or Provitamin A(beta-carotene), GSH

14. IDEAL ANTIOXIDANT THERAPY
 Not one antioxidant alone can lead to health benefits
but the combination, as found for example in fruits
and vegetables, is the active principle, leads to
synergistic effects.
Mol Nutr Food Res. 2007 Jul 18;

15. IDEAL ANTIOXIDANT THERAPY
 The clinical studies have shown that the Antioxidant
supplements which are high in ORAC contents are
very potent in action against the Oxidative Stress
and Free Radicals which are responsible for the
complications of the various Diseases in the
humans.

16. ANTIOXIDANT DEFENSES IN
HUMAN PLASMA AND LDL
Small Molecule Antioxidants Typical Plasma Conc.
• Water-Soluble: μM
Uric Acid 300
Ascorbic Acid (Vitamin C) 50
Albumin-Bound Bilirubin 15
Glutathione (GSH) < 2
• Lipid-Soluble (Lipoprotein): mol/mol LDL
α-Tocopherol (Vitamin E) 25 10
Ubiquinol-10 (Coenzyme Q10) 1.0 0.4
β-Carotene (Pro-Vitamin A) 0.5 0.2
Lycopene 0.5 0.2

17. DIABETES
 Diabetes mellitus is a metabolic disorder
characterized by hyperglycemia due to
 insufficiency of secretion (Type 1)
or
 utilization of endogenous insulin (Type 2)

18. ROS & DIABETES
 Increased oxidative stress is a widely accepted
participant in the development and progression of
diabetes and its complications
 Free radicals are formed disproportionately in diabetes
by glucose oxidation, on enzymatic glycation of proteins,
and the subsequent oxidative degradation of glycated
proteins.

19. ROS & DIABETES
 Abnormally high levels of free radicals and the
simultaneous decline of antioxidant defence
mechanisms can lead to damage of
 cellular organelles and enzymes,
 increased lipid peroxidation,
 and development of insulin resistance.
 These consequences of oxidative stress can
promote the development of complications of
diabetes mellitus

20. DIABETES: AFFECTS QUALITY OF LIFE
 Diabetes complications affecting the
 vascular system,
 kidney,
 retina, lens,
 peripheral nerves,
 Skin
 Complications are common and are extremely
costly in terms of longevity and quality of life.

21. CARDIOVASCULAR DISEASE
Oxidative damage is believed to be the
underlying mechanism in the etiology of
cardiovascular disease (CVD)
More recently, the multifaceted role of
oxidatively modified LDL has been
proposed as being instrumental in
atherogenesis

22. PREVALENCE OF CARDIOVASCULAR DISEASES
AGE 20 AND OLDER BY AGE AND GENDER
Note: These data include CHD, CHF, stroke and hypertension.
Source: CDC/NCHS. : 1988-94

23. INDIAN DATA

24. CARDIOVASCULAR DISEASE
 According to recent estimates, Cases of CVD may
increase from about 2.9 crore in 2000 to as many as
6.4 crore in 2015
 Deaths from CVD will also more than double.
 Most of this increase will occur on account of
coronary heart disease —AMI, angina, CHF
 and inflammatory heart disease
Source:—Burden of Disease in India (New Delhi, India), September 2005

25. RISING PREVALENCE AND MORTALITY
Forecasting the prevalence rate (%) of coronary heart disease (CHD) in India
Estimated mortality from coronary heart disease (CHD)

26. CHD ESTIMATES
Estimates and trends of coronary heart disease
(CHD) cases in various age groups

27. ATHEROSCLEROSIS
 Hardening, loss of elasticity, and
thickening of arterial walls with
narrowing of the lumen of the artery
 Principal cause of myocardial
infarction and stroke (heart and
brain attack)

28. OXIDATIVE MODIFICATION HYPOTHESIS OF ATHEROSCLEROSIS
Diaz, Frei et al. New Engl. J. Med. 1997;337:408-416

29. MECHANISMS OF ANTIOXIDANT ACTION IN ATHEROSCLEROSIS
Diaz, Frei et al. New Engl. J. Med. 1997;337:408-416

30. WHY ANTIOXIDANTS IN ATHEROSCLEROSIS?
 Inverse association between plasma
levels of carotenoids and the risk of
atherosclerosis in various vascular
territories support the hypothesis that
antioxidants protect against
atherosclerosis and other arterial
diseases
Atherosclerosis 153 (2000) 231-239

31. WHY ANTIOXIDANTS IN ATHEROSCLEROSIS?
 Inverse association between
plasma levels High serum levels of
total carotene, comprising alpha-
and beta-carotenes and lycopene,
may reduce the risk for
cardiovascular disease mortality
J Epidemiol. 2006 Jul;16(4):154-60.

32. CHRONIC FATIGUE
Intractable or chronic fatigue lasting
more than 6 months that is not reversed
by sleep is the most common complaint
of patients seeking medical care
 It is also an important secondary
condition in many clinical diagnoses and
occurs naturally during aging

33. CHRONIC FATIGUE
 Most patients understand fatigue as a loss of
energy and inability to perform even simple
tasks without exertion.
 Many medical conditions are associated with
fatigue, including respiratory, coronary,
musculoskeletal, and bowel conditions as well
as infections and cancer

34. CHRONIC FATIGUE:ETIOLOGY
Fatigue is related to cellular energy systems found
primarily in the cells' mitochondria.
Damage to mitochondrial components, mainly by
ROS oxidation, can impair their ability to produce high-
energy molecules such as ATP.
This occurs naturally with aging and during chronic
illnesses, where the production of ROS can cause
oxidative stress and cellular damage, resulting in
oxidation of lipids, proteins and DNA

35. Mitochondria

36. CHRONIC FATIGUE : TREATMENT
Antioxidant
to Preserve mitochondrial function
Prevent oxidative membrane damage
Prevent oxidation of lipids and proteins
LRT to generate energy

37. prostate cancer prevention and therapy

38. Normal Prostate

39. Prostate Cancer

40. ANTIOXIDANTS IN PROSTATE CANCER
 In prostate cancer, a study has demonstrated inhibition of cell
line proliferation in the presence of physiological concentration
of lycopene in combination with vit.E
pastori m,pfander H, Biophys Res Commun,
1998;250:582-585

41. PROSTATE CANCER
 Intake of exogenous antioxidants (vitamins
E, C, beta-carotene and others) could
protect against cancer and other
degenerative diseases in people with innate
or acquired high levels of ROS.
 J Am Coll Nutr October 2001 vol. 20 no. suppl 5 464S-472S

42.  Chemoprevention of prostate cancer can be
achieved with nutritional doses of antioxidant
vitamins and minerals (Mainly Vit C, Vit E, beta-
carotene, selenium & Zinc)
Int J Cancer 2005

43. PREGNANCY & ROS
 Pregnancy places increased demands on the mother
to provide adequate nutrition to the growing
conceptus. A number of micronutrients function as
essential cofactors for or themselves acting as
antioxidants.
 Oxidative stress is generated during normal placental
development; however, when supply of antioxidant
micronutrients is limited, exaggerated oxidative stress
within both the placenta and maternal circulation
occurs, resulting in adverse pregnancy outcomes.
Oxidative Medicine and Cellular Longevity Volume 2011 (2011),

44. PLACENTA AND UMBILICAL CORD

45. PRE-ECLAMPSIA & IUGR
 Pre-eclampsia is a human pregnancy
specific
disorder that adversely affects
 the mother by vascular dysfunction
 the fetus by intrauterine growth restriction
Etiology is unknown

46. PREECLAMPSIA & IUGR
 Pregnancy induced hypertension (PIH) may be
estimated to develop in 8–10% women
 Preeclampsia in 2–3%
 Reduced gestation period (Preterm delivery)
 Underweight Baby

47. ANTIOXIDANTS IN PREGNANCY
 Reduces pre-eclampsia
 Reduces incidence of PIH
 Reduces incidences of IUGR
 Facilitates full-term delivery

48. BREAST CANCER
 Breast cancer is the most common cancer and the
second leading cause of cancer-related death
among women

49. BREAST CANCER
 Excess production of free radicals and/or deficiency of the
antioxidant defence system can result in oxidative stress,
causing damage to DNA and other molecules
 Over time, such damage may become irreversible and may
lead to diseases such as cancer.
 There is evidence showing that oxidative stress and lipid
peroxidation are linked to the etiology of breast cancer

50. ANTIOXIDANTS & BREAST CANCER
 Antioxidants ―mopping up‖ free radicals decrease
oxidative stress and oxidative DNA damage
 Antioxidants may selectively induce apoptosis in
cancer cells but spare normal cells, and inhibit cell
proliferation

51. WHY ANTIOXIDANTS IN BREAST CANCER?
 supplementation of certain antioxidants such as
beta-carotene, vitamin C, vitamin E and zinc may
reduce the risk of breast cancer
Pan et al. BMC Cancer 2011, 11:372

52. MALE INFERTILITY: OVERVIEW
1. Male Infertility
2. Oxidative Stress and Male Infertility
3. Antioxidant Therapy for Male
Infertility

53. MALE INFERTILITY: PREVALENCE
15% of couples suffer from infertility
A male factor is responsible for the couple
infertility in 30-50% of cases
~5-10% of males are infertile or sub-fertile

54. ETIOLOGY OF MALE INFERTILITY
Multi-factorial Prevalence
Varicocele 35%
Idiopathic 25%
Infection – genito-urinary tract 10%
Genetic 10%
Endocrine 1 - 5%
Immunologic 1 - 5%
Obstruction 1 - 5%
Developmental 1 - 5%
Lifestyle: smoking, diet, heat ???%

55. VARICOCELE
 Dilated testicular veins
 Mechanisms of Injury:
 Increased Heat
 Venous Stasis

56. OXIDATIVE STRESS IN MALE
INFERTILITY
Multi-factorial
Varicocele
Idiopathic
Infection Oxidative stress is due to the
elaboration
Genetic of
Endocrine ROS (reactive oxygen species)
Immunologic
Obstruction
Developmental
Lifestyle
de Lamirande et al, Fertil Steril, 1995
Wesse et al, J Urol, 1993
Hendin et al, J Urol, 1999
Mazzilli et al, Fertil Steril, 1994
Vicari et al, Hum Reprod, 1999

57. ROLE OF ANTIOXIDANTS IN SEMEN
Function
 Protect normal sperm from
ROS-producing sperm
 Protect normal sperm from
WBC-derived ROS
 Suppress premature sperm maturation
Site of Action
 Male reproductive tract

58. ROS AND NORMAL SPERM FUNCTION
Low levels of oxidative stress in vitro enhance:
 sperm hyperactivation
 sperm capacitation
 acrosome reaction
 sperm-egg binding
 sperm-egg fusion
 Fertilization
Bize et al, Biol Reprod, 1991
de Lamirande et al, Int J Androl, 1993
Griveau et al, Int J Androl, 1994, 1995
Zini et al, J Androl, 1995
Kodama et al, J Androl, 1996
Aitken et al, Biol Reprod, 1998

59. MALE INFERTILITY:
Oxidative stress is important in Male
Reproduction
 25% of infertile men have high levels of semen ROS
 Spermatogenesis is very sensitive to oxidative stress
 Lipid & DNA oxidation/damage are key pathologic events

60. ANTIOXIDANTS IN MALE INFERTILITY:
ADDITIONAL EVIDENCE
Oral antioxidant (containing Vit C & E, Zinc,
Selenium, Carotenoids) improve sperm quality
and pregnancy rate .
Biomed Online 2010

61. ANTIOXIDANTS IN MALE INFERTILITY
 Reaches in high concentration
 Improves acrosome reaction
 Enhances
 Sperm morphology
 Sperm motility
 Sperm count

62. EYE DISORDERS
 Glaucoma – Restricts the vision angle
 Cataract – Blurred vision
 AMD – Degeneration of eye

63. AMD
 Age-Related Macular Degeneration (AMD) is a
degenerative disorder of the macula, the central
part of the retina.
 Late-stage AMD results in an inability to read,
recognize faces, drive, or move freely.

64. AMD
 The prevalence of late AMD steeply increases with
age
 AMD is expected to increase in the next 20 years
by more than 50%

65. ANTIOXIDANTS IN AMD
 A high dietary intake of beta carotene, vitamins C
and E, and zinc was associated with a substantially
reduced risk of AMD in elderly persons.
JAMA. 2005;294:3101-3107

66. USP’s of antioxidants:
•Destroy the free radicals that damage cells.
•Promote the growth of healthy cells.
•Protect cells against premature, abnormal aging.
•Help fight age-related macular degeneration.
•Provide excellent support for the body’s immune system, making it
an effective disease preventative.
No Matter What Your Age…You Need Antioxidants!