Antioxidant presen13 /certified fixed orthodontic courses by Indian dental academy


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Antioxidant presen13 /certified fixed orthodontic courses by Indian dental academy

  1. 1. Antioxidants INDIAN DENTAL ACADEMY Leader in continuing dental education
  2. 2. Table of contents • • • • • Introduction Definitions Free radicals Antioxidants Chemo prevention
  3. 3. Free radicals in disease pathogenesis System/Organ cvs brain kidney liver lung skin eye blood multi-organ diseases Disease process atherosclerosis alzeheimers renal graft rejection cirrhosis oxidant pollutants solarionizing radiation catarcts fanconi’s anaemia nutritional deficiences
  4. 4. Definitions • Oxidant-electron acceptor in an oxidationreaction. • Oxidation-a chemical reaction in which electrons from one reactant are transferred to the other reactant. • Oxidative stress-a pathological change seen in a living organism in response to excessive levels of cytotoxic oxidants & free radicals in the environment.
  5. 5. • Free radicals-unpaired electrons ,highly reactive & unstable enters into reaction with inorganic/organic chemicals-PROTEINS,LIPIDS,CHO,particularly molecules in membranes & nucleic acids.
  6. 6.
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  8. 8. ROS reaction with bio-molecules • DNA- attack nucleotide base/deoxyribose chain results in strand breaks,cell killing & neoplastic transformation of cells(Cheeseman &Slater,93) • PROTEIN- promotes cross-linking of amino acids results in fragmentation of peptide chain (Chevion & Stadman,91) • LIPID Cell membranes are attacked by oxidising agentslipid peroxidation(Cheeseman,93). • Malondialdehyde(MDA)-formed by peroxidation of unsaturated fatty acid, mda reacts with thiobarbituric acid---TB REACTIVE SUBSTANCES ASSAY(TBRSA)
  9. 9. ANTIOXIDANT SYSTEMS: • Substance which prevents damage caused by oxidation.
  10. 10. MODE OF ACTION • Chain breaking tocopherol,acts in lipid phase to trap”ROD” radical. • Reducing the conctn of • Scavenging initiating dismutase,acts in aqueous phase to trap superoxide free radicals. • Chelating the transition metal catalysts. Eg: Transferrin,to check iron induced stress
  11. 11. CLASSIFICATION-Modified by Fischer,1988 • Enzymes Antioxidant • Superoxide dismutase (SOD) MitochondrialCytoplasmic Extracellular • Role :Dismutates O2·⁻ to H2O2 . • Remarks :Contains Manganese (Mn.SOD) , Copper & Zinc (CuZnSOD),Copper (CuSOD) • Catalase :Dismutates H2O2 to H2O .Tetrameric hemoprotein present in peroxisomes. • Glutathione peroxidase (GSH.Px) ..Removes H2O2 and lipid peroxides . • Selenoproteins (contains Se2+) Primarily in the cytosol also mitochondria .Uses GSH
  12. 12. NON ENZAMATIC ANTIOXIDANTS • Vitamins • Alpha tocopherol :Breaks lipid peroxidation Lipid peroxide and O2·⁻ and ·OH scavenger .Fat soluble vitamin. • Beta carotene: Scavenges ·OH, O2·⁻ and peroxy radicals Prevents oxidation of vitamin A Binds to transition metals. • Ascorbic acid :Directly scavenges O2·⁻, ·OH, and H2O2, Neutralizes oxidants from stimulated neutrophils .Contributes to regeneration of vitamin E Water soluble vitamin
  13. 13. Other Antioxidants • Retinoids- have antioxidant properties(Prasad,89)but main function as antiproliferatives. • CoQ10-Ubiquinone,found in all living cells.Has antioxidant and enhances immune defenses. • Albumin-scavenges free radcals(Halliwlel,94) • Drugs-antioxidant effects(Reilly et al,91)xanthine oxidase inhibitors,eg allopurinol,folic acid, • NADPH,calcium channel blocker
  14. 14. Antioxidants and trace elements • Selenium - protective role against cancer (Schwartz and Foltz,1957) • Nutrition role of selenium - essential component of enzyme glutathione peroxidase- participate in AO protection of cells(Rotruck et- al , 1973) • Anticarcinogenic effect of SE- se supplements -reduce cancer risk, acts as modifier of cancer risk.
  15. 15. Where do you find Antioxidants *Beta Carotene: in foods that are orange in color such as sweet potatoes, carrots, cantaloupe, squash, pumpkin and mangos as well as in some green leafy vegetables *Lutein: in green leafy vegetables such as collard greens, spinach, and kale *Lycopene: in tomatoes, watermelon, papaya, apricots, and pink grapefruit *Selenium: in rice, wheat and brazil nuts *Vitamin A: in liver, sweet potatoes, carrots, milk, egg yolks and mozzarella cheese *Vitamin E: in almonds, wheat germ, safflower, corn, and soybean oils, mangos, nuts, and broccoli
  16. 16. Sources of Antioxidants *Vitamin C: in fruits and vegetables, cereals, beef, poultry and fish
  17. 17. Antioxidants and Cancer -Tumor initiation involves the exposure of normal cells to chemical or physical carcinogens that alter the DNA of thecells -The altered genotype of the cell is considered irreversible, but the initiated phenotype is not fully expressed except in the presence of a promotor -Promotors cause the clonal expansion of initiated cells-Tumor initiation and promotion together usually only produce benign growths-The third stage,malignant conversion is uncontrolled cellular growth which is only treatedby outside intervention -Several studies show that antioxidants may slow or possibly prevent the development of cancer, however in recent years clinical trials reached inconsistent conclusions *Five large scale clinical trials in the 1990s reached differing conclusions about the effects of antioxidants on cancer
  18. 18. Clinical Trial 1: Chinese Cancer Prevention Study (1993) -The results showed that a combination of beta-carotene, vitamin E, and selenium significantly reduced incidence of both gastric cancer and cancer overall 2: Alpha-Tocopherol/Beta-Carotene Cancer Prevention Study (1994) -Lung cancer rates of Finnish male smokers increased significantly with beta-carotene intake and were not affected by vitamin E 3: Beta-Carotene and Retinol Efficacy Trial (1994) -Also demonstrated a possible increase in lung cancer associated with antioxidants 4: 1996 Physician’s Health Study I -No change in cancer rates associated with beta-carotene taken by U.S. male physicians 5: 1999 Women’s Health Study -No benefit or harm from beta-carotene supplementation, vitamin E research is ongoing
  19. 19. ANTIOXIDANTS AND CARDIOVASCULAR DISEASE There is a wide range of cardiovascular diseases: Coronary Artery Disease (CAD) Myocardial Infarction (MI) – heart attack Cardiac Ischemia – insufficient blood and oxygen supply to a portion of the heart muscle, most commonly caused by CAD Atherosclerosis – development of fatty buildups in the arteries
  20. 20. TREATMENT & PREVENTION OF CVS • Ecological and epidemiological evidence suggests that high consumption of fruits and vegetables is associated with a decreased risk for CD • Fruits and vegetables, along with teas and red wines are rich in antioxidants • Therefore, researchers logically assumed that antioxidants played a role in this protective cardiovascular effect
  21. 21. OXIDATIVE DAMAGE & CVS • There is ample evidence that oxidative damage is involved in the pathology of atherosclerosis • LDL oxidation leads to uptake by macrophages and formation of the foam cell and creates oxidized lipids that have a pro-inflammatory response • Researchers began to investigate the effects of antioxidants to reverse the effects of ROS and oxidative
  22. 22. ANTIOXIDANTS & DICHOTOMY • Epidemiological evidence shows that antioxidants have a protective or therapeutic effect on CD • Clinical trials support antioxidants as beneficial, neutral, and, in some cases, harmful • The controversy between research shows that antioxidant mechanisms in response to oxidative damage are not completely understood
  23. 23. CASE STUDIES:ANTIOXIDANTS ARE BENEFICIAL • Health Professionals’ Follow-up study: – >39,000 males, 4 year follow-up – Β-carotene intake is associated with reduced risk of coronary events; inverse relationship between duration of vitamin E supplement use and risk in smokers • Nurses’ Health Study (Stampfer et al): – >87,000 women, < 8 year follow-up – Coronary events and vitamin E intake are inversely related, 43% lower in supplement users vs. nonusers; inverse relationship between risk and duration of supplement use
  24. 24. ANTIOXIDANTS ARE BENEFICIAL • National Health and Nutrition Examination Survey (Enstrom et al) – Inverse relationship between vitamin C intake and coronary risk; decreased death from coronary heart disease over 10 year follow-up • Cambridge Heart AntiOxidant Study (CHAOS) – ~9,500 subjects age 55 and over with both symptomatic and asymptomatic CD, secondary prevention trial, lasted 17 months – Coronary disease patients benefited from naturally occurring vitamin E at 2 dose levels – this leads researchers to believe there is a difference between natural and supplemental antioxidants
  25. 25. ANTIOXIDANTS -NO BENEFIT/HARM Physicians’ Health Study >29,000 male physicians in the US were randomized to â-carotene, aspirin, both, or neither for 12 years No significant benefit or harm of â-carotene on cardiovascular disease Women’s Health Study >40,000 women 45 and older, primary prevention study on the effects of â-carotene, vitamin E and low-dose aspirin on major cardiovascular endpoints 2-year analysis showed no effect from âcarotene supplements
  26. 26. ANTIOXIDANTS ARE HARMFUL  α-tocopherol β-carotene Study (ATBC) Tested α-tocopherol, β-carotene, both or neither for 5-8 years in >29,000 male smokers No reduction in cardiovascular events in any treatment; increase in risk of death from hemorrhagic stroke from vitamin E, increase in mortality from ischemic heart disease  β-carotene and Retinol Efficacy Trial (CARET) Studied the effects of combination of β-carotene and a form of retinol Increased risk of cardiovascular disease mortality
  27. 27. PROPOSALS & RECOMMENDATIONS • AHA does not recommend antioxidant supplements, instead following the Food Guide Pyramid is recommended • Many researchers have criticized the study designs of all studies: subjects chosen (at risk vs. not at risk for CVD), study length, dosage, etc. • Distribution of other nutrients in foods is similar to that of antioxidants, thus the trend that fruits and vegetables reduce cardiovascular disease could be caused by mechanisms other than their antioxidant vitamin content, for example: lowering of blood pressure and dietary factors such as trace elements found to act as antioxidants in the diet
  28. 28. ANTIOXIDANTS & EXERCISE • • • • • • • ENDURANCE EXERCISE(ultra distance race,high altitude training)-free radicalsdamaging to muscles & tissues Regular exercise-enhances-antioxidants system-protects body. EXPERIMENTAL STUDIES-conflicting Most DATA-VIT-E-protective RECOMMENDATION-Balanced program with reglr exercise & 5 serving of fruit/veg/day Demanding race/hg altitude training-VIT-E supplmts, 100-200IU,appxmtly 10 times the RDA/DAY
  29. 29. ANTIOXIDANTS & AGING • EXCESS FREE RADICALS-cellular damage b,coz fatty acids,protein are lost in cell membraneUNSTABLE-imbalance b/w flow of nutrient in & out of cells. • CEL MEMBRANE-OXIDISED-HARDENS-nutrients cannot go into cell. • PUNCTURES-cell collapses-cell fluids drains outAGING-WRINKLES-SAGGY & LEATHERY
  30. 30. ANTIOXIDANTS IN CHEMOPREVENTION • • • CHEMOPREVENTIONpharmocological intervention with specific nutrient or other chemicals to suppress or prevent the development of disease. CLASSIFIED -BLOCKING AGENTS-inhibit tumor initiation SUPPRESSING AGENTSinhibit tumor promotion/progression
  31. 31. ANTIOXIDANTS IN ORAL MEDICINE • USES IN ORAL LESIONS • LEUKOPLAKIA-SILVERMAN(1960)evaluated vit A(13cRA)topical application,lesions relapsed,as soon treatment was discontinued. • Side effects-dry skin,xerostomia,hyper triglyceridemia,chelitis • STICH ET AL(1991)administrated vit A(60mg/wk)fr 6mocomplete remission of OLK in 57%,reduction of micro-nuclei cells in 96% of tobacco chewers. • Beta-Carotene (2.2mmol/wk)-remission 14.8%& reduction of micronuclei cells in 98%. Vit A (COMPLETELY) & BETA CAROTENE(50%) suppressed formation of OLK within 6 mo trial period.But relapsed once treatment was dis continued of drug.
  32. 32. • SINGH et al(2003)administered lycopene in treatment of . OLK,in 3 gp(gpA,gpB,gpC)were given 8mg/day,4mg/day,0(placebo),mean response was 80%,66.25%,12.5% resptly,patients recovrd in gp A,gp B.This study confirmed lycopene was 3 fold more effective than beta carotene in preventing cell death by quenching NOO- radicals,it also protects DNA damage induced by H2O2. • LICHEN PLANUS -Treated with ETRETINATE,which is synthetic retinol,but clinical success inconsistent,relapse rate was more than 50%within 3 mo.
  33. 33. • ORAL SUBMUCOUS FIBOSIS • ROLE OF OXIDATIVE STRESS AND ANTIOXIDANTS IN AETIOPATHOGENESIS ANDMANAGEMENT OF ORAL SUBMUCOUS FIBROSIS (GUPTA et al,2004).Lipid peroxidation product, malonaldehyde (MDA) and antioxidants were estimated in plasma and erythrocytes of 34 cases of oral submucous fibrosis (OSMF) of different grades with equal numberof healthy controls to evaluate the association of reactive oxygen species (ROS) and OSMF. plasma MDA was found to be significantly higher in patients ,as compared to controls ,plasma beta carotene and vitamin E levels were found to be decreased significantly in patients, with respect to healthy controls. After 6 weeks of oral administration of beta-carotene and vitamin E, patients showed increase in plasma level of these two antioxidants along with decrease in MDA level associatedwith clinical improvement.
  34. 34. ANTIOXIDANTS IN PREVENTION OF SECOND PRIMARY TUMORS • Patients with SCC of H&N CANCER, • Hong et al (1990)administered 50-100mg of 13cRA/d given to pts with treated SCC of oral cavity,pharynx resulted in fewer second primary cancer.
  35. 35. SUPPLEMENTS AVAILABLE • • • • • • • • • • Indications-metabolic disease,CBV,CVS,neurological diseases,degenerative disease of eye,oral lesions Special precaution-high doses of beta carotene-yellowish of skin(carotenimia) side effects-diarhoea,yellowing of palms,etc. Brands available are ADENT(spirulina) tab-500mg ALA-100(alpha-lipoic acid)-cap15mg ANTOXID-1 TAB -3 times/d-1st 2 months,folwd by 1cap d BETA SCLERBION BIO-E OXYACE
  36. 36. COMMON WAY TO PREVENT DISEASES • • • Take Daily supplements of antioxidants Stop Smoking Diet rich in fruits and vegetables (i.e. green leafy veggiescollards, kale, spinach, and broccoli
  38. 38. Thank you For more details please visit