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Antioxidant medical


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Antioxidant medical

  1. 1. ANTIOXIDANT Narveer Shekhawat
  2. 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. 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. 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. 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. 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. 7. ROS IS IMPLICATED IN  Diabetic complications  CVD – Atherosclerosis  Debility – Chronic fatigue  Prostate cancer  Infertility  Pregnancy complications  Breast Cancer  Eye Disorders
  8. 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
  10. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 23. INDIAN DATA
  24. 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. 25. RISING PREVALENCE AND MORTALITY Forecasting the prevalence rate (%) of coronary heart disease (CHD) in India Estimated mortality from coronary heart disease (CHD)
  26. 26. CHD ESTIMATES Estimates and trends of coronary heart disease (CHD) cases in various age groups
  27. 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. 28. OXIDATIVE MODIFICATION HYPOTHESIS OF ATHEROSCLEROSIS Diaz, Frei et al. New Engl. J. Med. 1997;337:408-416
  29. 29. MECHANISMS OF ANTIOXIDANT ACTION IN ATHEROSCLEROSIS Diaz, Frei et al. New Engl. J. Med. 1997;337:408-416
  30. 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. 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. 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. 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. 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. 35. Mitochondria
  36. 36. CHRONIC FATIGUE : TREATMENT Antioxidant to Preserve mitochondrial function Prevent oxidative membrane damage Prevent oxidation of lipids and proteins LRT to generate energy
  37. 37. prostate cancer prevention and therapy
  38. 38. Normal Prostate
  39. 39. Prostate Cancer
  40. 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. 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. 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. 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),
  45. 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. 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. 47. ANTIOXIDANTS IN PREGNANCY  Reduces pre-eclampsia  Reduces incidence of PIH  Reduces incidences of IUGR  Facilitates full-term delivery
  48. 48. BREAST CANCER  Breast cancer is the most common cancer and the second leading cause of cancer-related death among women
  49. 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. 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. 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. 52. MALE INFERTILITY: OVERVIEW 1. Male Infertility 2. Oxidative Stress and Male Infertility 3. Antioxidant Therapy for Male Infertility
  53. 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. 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. 55. VARICOCELE  Dilated testicular veins  Mechanisms of Injury:  Increased Heat  Venous Stasis
  56. 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. 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. 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. 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. 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. 61. ANTIOXIDANTS IN MALE INFERTILITY  Reaches in high concentration  Improves acrosome reaction  Enhances  Sperm morphology  Sperm motility  Sperm count
  62. 62. EYE DISORDERS  Glaucoma – Restricts the vision angle  Cataract – Blurred vision  AMD – Degeneration of eye
  63. 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. 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. 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. 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!