Free radicals and antioxidants

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Free radicals,antioxidants, damage caused by free radicals, prevention

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Free radicals and antioxidants

  1. 1. Free Radical Injury & Antioxidants
  2. 2. Introduction It is believed that life has originated from basic chemicals by free radical reaction, largely initialled by ionising radiation from sun. Paradoxically the same reactions creating life may also be responsible for many diseases, ageing and death.
  3. 3. Free Radicals <ul><li>“ any species capable of independent existent that contains one or more unpaired electrons ” </li></ul><ul><li>Example : </li></ul><ul><li>Radicals can be formed by… </li></ul><ul><li>The LOSS of a single electron from a non-radical, or by the GAIN of a single electron by a non-radical </li></ul><ul><li>The breakage of covalent bond ‘homolytic fission’ </li></ul>A B A + B     H 2 O H + OH   Example : Hydroxyl radical ( OH) O    H     
  4. 4. Free Radical s (FRs) <ul><li>These are highly reactive chemical entities that have a single unpaired electron in their outer most orbit. </li></ul><ul><li>Under certain conditions can be highly toxic to the cells. </li></ul><ul><li>Generally unstable and try to become stable, either by accepting or donating an electron . </li></ul>
  5. 5. <ul><li>Therefore if two FRs react, they neutralise each other. </li></ul><ul><li>However, if the FRs react with stable molecules, there is generation of more free radicals. </li></ul><ul><li>This character enables the FR s to participate in auto catalytic chain reactions, </li></ul><ul><ul><li>Molecules with which they react are themselves converted to free radicals to propagate the chain of damages. </li></ul></ul>
  6. 6. Free Radical Nomenclature <ul><li>A free radical is denoted by a superscript dot to the oxygen (or carbon) </li></ul><ul><ul><li>e.g., HO  , NO  ,  CH 3 </li></ul></ul><ul><li>If a free radical is a charged species, the dot is put and then the charge </li></ul><ul><ul><li>e.g., O 2  - </li></ul></ul><ul><li>(See “Free Radical Nomenclature, Suggestions” by </li></ul><ul><li>Buettner, G.R., Schafer, F.Q.) </li></ul>
  7. 7. Reactive Oxygen Species <ul><li>Radicals – Hydroxyl radical </li></ul><ul><li>Molecules – Hydrogen peroxide </li></ul><ul><li>Ions – Hypochlorite ion </li></ul><ul><li>Superoxide anion – which is both ion and radical </li></ul> Superoxide anion ( O 2 - ) O     O         -  Hydroxyl radical ( OH) O    H      Hydroxy anion (OH - ) O    H     -  Hydrogen peroxide (H 2 O 2 ) O     O       H H     Hypochlorite anion (OCl - ) O     Cl           - Oxygen (O 2 ) O     O        
  8. 8. Types of Free Radicals <ul><li>Oxygen-centered radicals </li></ul><ul><ul><li>Singlet oxygen, superoxide, hydroxyl radicals </li></ul></ul><ul><li>Sulfur-centered radicals </li></ul><ul><ul><li>Thiyl radical (RS • ) </li></ul></ul><ul><li>Carbon-centered radicals </li></ul><ul><ul><li>• CCl 3 , CH 2 • CHOH </li></ul></ul><ul><li>Nitrogen-centered radicals </li></ul><ul><ul><li>NO • , R 2 NO • </li></ul></ul>
  9. 9. Superoxide Radicals <ul><li>Generation of superoxide (O 2  - ) </li></ul><ul><ul><li>The addition a single electron to the ground-state molecule (O 2 + e - O 2  - ) </li></ul></ul><ul><li>Biological generation of O 2  - </li></ul><ul><ul><li>Mitochondrial electron transport chain </li></ul></ul><ul><ul><li>Enzymatic reduction of oxygen (O 2 ) </li></ul></ul><ul><ul><li>Xenobiotic metabolisms (redox cycling) </li></ul></ul><ul><ul><li>Respiratory burst (phagocytes) </li></ul></ul>
  10. 10. Mitochondrial Electron Transport Chain <ul><li>The most important source of O 2  - in vivo in most aerobic cells </li></ul>
  11. 11. Superoxide Production from Mitochondrial Electron Transport Chain ‘ Leaking’ of electron (to oxygen) during electron transport leads to the formation of O 2  - (O 2 + e- O 2  - )
  12. 12. <ul><li>Passage of electrons from Complex I to QH 2 involving the radical Q · as an intermediate. </li></ul>
  13. 13. 0.1% to 4% of the O 2 used actively by respiring mitochondria forms O 2 - --- more than enough to have lethal effect on the cell unless the free radical is quickly disposed off.
  14. 15. <ul><li>The passage of electrons in the complex II from succinate to ubiquinone </li></ul>
  15. 16. Complex III
  16. 17. Biological Generation of Superoxide <ul><li>Enzymatic reduction of oxygen </li></ul><ul><li>Xanthine/hypoxanthine Uric acid </li></ul><ul><li>Redox cycling : Paraquat (Xenobiotic) </li></ul>O 2 O 2  - XOD [XOD = xanthine oxidase] N • N CH 3 H 3 C + N N CH 3 H 3 C + Oxidized cytochomre P450 reductase Reduced cytochomre P450 reductase NADPH NADP O 2 O 2  - Paraquat e - +
  17. 18. Respiratory Burst <ul><li>Myeloperoxidase </li></ul><ul><ul><li>Oxidizes Cl - to hypochlorous acid </li></ul></ul><ul><ul><li>Chronic granulomatous disease </li></ul></ul><ul><li>NADPH oxidase enzyme </li></ul>• • NADPH NADP + O 2 O 2  - NADPH NADP + O 2 O 2  - outside inside . . . . Phagocytic vacuole (phagosome)
  18. 19. Respiratory Burst Myeloperoxidase Activity
  19. 20. Respiratory Burst <ul><li>NADPH oxidase complex </li></ul><ul><li>Cytoplasmic proteins </li></ul><ul><li>(p47, p67, gp91, p22) </li></ul><ul><li>NADPH NADP + + H + </li></ul><ul><li>Electron is transferred </li></ul><ul><li>from NADPH to O 2 , resulting </li></ul><ul><li>in the formation of O 2  - </li></ul>[NADPH : Reduced Nicotinamide Adenine Dinucleotide Phosphate]
  20. 21. Hydrogen Peroxide <ul><li>Not a free radical but ROS(reactive oxygen species) </li></ul><ul><li>Formed in the cell by dismutation reactions by </li></ul><ul><ul><li>Spontaneously during respiratory burst </li></ul></ul><ul><ul><li>By enzymes Eg: Superoxide dismutase </li></ul></ul>
  21. 22. Hydrogen Peroxide
  22. 23. Hydroxyl Radical (HO  ) <ul><li>Highly reactive oxygen radicals </li></ul><ul><li>Formation of hydroxyl radicals in biological systems </li></ul><ul><ul><li>Ionizing radiation </li></ul></ul><ul><ul><li>Reaction of metal ions with hydrogen peroxide (Fenton reaction) </li></ul></ul><ul><ul><li>Formation of hydroxyl radical from ozone (O 3 ) </li></ul></ul><ul><li>Reactions of hydroxyl radicals </li></ul><ul><ul><li>Hydrogen atom abstraction </li></ul></ul><ul><ul><li>Addition </li></ul></ul><ul><ul><li>Electron transfer </li></ul></ul>
  23. 24. Fenton Reaction <ul><li>Discovered by Fenton (1894) </li></ul><ul><li>“ A mixture of hydrogen peroxide and an iron(II) salts causes the formation of hydroxyl radical ” </li></ul><ul><li>Fe 2+ + H 2 O 2 intermediate complex Fe 3+ + OH - + HO  </li></ul><ul><li>Fe 3+ + H 2 O 2 intermediate complex Fe 2+ + O 2  - + 2H + </li></ul><ul><li>Haber-Weiss reaction </li></ul><ul><li>Fe 2+ + H 2 O 2 Fe 3+ + OH - + HO  </li></ul><ul><li>Fe 3+ + O 2  - Fe 2+ + O 2 </li></ul><ul><li>Net : O 2  - + H 2 O 2 O 2 + HO  + OH - </li></ul>metal catalyst
  24. 25. Nitrogen-Centered Radicals <ul><li>Nitric oxide (NO  ) </li></ul><ul><ul><li>Endothelial derived-relaxing factor (EDRF) </li></ul></ul><ul><ul><li>Generated from the catalysis of L-arginine by nitric oxide synthase (NOS) enzymes </li></ul></ul><ul><ul><li>Functions </li></ul></ul><ul><ul><ul><li>Vascular function, platelet aggregation, immune response, neurotransmitter, signal transduction </li></ul></ul></ul><ul><ul><ul><li>cytotoxicity </li></ul></ul></ul><ul><ul><li>NO  + O 2  - ONOO - (highly toxic) </li></ul></ul>
  25. 26. <ul><li>In the absence of L-arginine and BH 4 (tetrahydrobiopterin), the activation of molecular by NOS results in a divalent reduction of O 2 to yield superoxide anions and hydrogen peroxide. </li></ul>L-arginine L-citrulline NO  + NOS BH 4
  26. 29. Sources of Free Radicals <ul><li>Endogenous sources of free radicals </li></ul><ul><ul><li>Oxidative metabolic transformation </li></ul></ul><ul><ul><ul><li>Mitochondrial respiratory chain </li></ul></ul></ul><ul><ul><ul><li>Oxygen burst (respiratory burst) during phagocytosis </li></ul></ul></ul><ul><ul><ul><li>Eicosanoid synthesis </li></ul></ul></ul><ul><ul><ul><li>Enzymatic reactions (oxygenases, oxidases) </li></ul></ul></ul><ul><ul><li>Xenobiotic metabolism (redox cycling) </li></ul></ul>
  27. 30. Sources of Free Radicals <ul><li>Exogenous sources of free radicals </li></ul><ul><ul><li>Ionizing radiation </li></ul></ul><ul><ul><li>Ultraviolet radiation </li></ul></ul><ul><ul><li>Ultrasound </li></ul></ul><ul><ul><li>Chemicals, tobacco smoke, etc </li></ul></ul>
  28. 31. Roles of Free Radicals in Biological Systems <ul><li>Enzyme-catalyzed reactions </li></ul><ul><li>Electron transport in mitochondria </li></ul><ul><li>Signal transduction & gene expression </li></ul><ul><li>Activation of nuclear transcription factors </li></ul><ul><li>Oxidative damages of molecules, cells, tissues </li></ul><ul><li>Antimicrobial actions </li></ul><ul><li>Aging & diseases </li></ul>
  29. 33. Cell Signaling
  30. 34. Oxidative Stress <ul><li>Damages caused by free radicals/reactive oxygen species </li></ul><ul><li>Cellular damages at different levels (membrane, proteins, DNA, etc) lead to cell death, tissue injury, cellular toxicity, etc </li></ul><ul><li>Reduction of antioxidants </li></ul>
  31. 35. Oxidative Stress Non-enzymatic sources Mitochondrial respiratory chain Glucose autoxidation Enzymatic sources NADPH oxidase Xanthine oxidase Cyclooxygenase O 2 O 2  - NO  ONOO - SOD H 2 O 2  OH H 2 O + O 2 GSH GSSG Fenton reaction (Fe or Cu) Catalase GPx
  32. 36. Free Radical Toxicity <ul><li>Causes of free radical toxicity </li></ul><ul><ul><li>Increase production of free radicals </li></ul></ul><ul><ul><li>Decrease level of defense system (e.g., antioxidants) </li></ul></ul><ul><li>Lipid peroxidation </li></ul><ul><li>DNA damage </li></ul><ul><li>Protein oxidation </li></ul>
  33. 37. Lipid Peroxidation <ul><li>Initiation of first-chain reaction </li></ul><ul><ul><li>Abstraction of H + by ROS ( • OH) </li></ul></ul><ul><ul><li>Formation of lipid radical (LH • ) </li></ul></ul><ul><ul><li>Formation of peroxyl radical (LOO • , ROO • ) </li></ul></ul><ul><li>Propagation </li></ul><ul><ul><li>H + abstraction by lipid peroxyl radical (LOO • ) </li></ul></ul><ul><li>Termination </li></ul><ul><ul><li>Radical interaction non-radical product </li></ul></ul>
  34. 38. Molecular rearrangement Conjugated diene Lipid hydroperoxide Cyclic peroxide Cyclic endoperoxide • • -H Hydrogen abstraction I O 2 Oxygen uptake Peroxy radical: abstract H• rom another fatty acid causing an autocatalytic chain reactions Initiation Propagation (LH•) (LOO•) • • O O O O H • H P I P
  35. 39. Products of Lipid Peroxidation Reactive Oxygen Species Lipid peroxides Alkanes Conjugated dienes Aldehyde products Malondialdehyde (MDA) n -aldehydes  ,  -unsaturated aldehydes
  36. 40. Oxidative DNA Damage <ul><li>Correlation with cancers and diseases </li></ul><ul><li>Oxidative DNA lesions by </li></ul><ul><ul><li>Direct attack </li></ul></ul><ul><ul><li>Indirect activation of endonuclease enzymes </li></ul></ul><ul><li>Oxidative modification of bases – mutation </li></ul><ul><li>Oxidative modification of sugar moieties – DNA strand break </li></ul>
  37. 41. A computer image depicts a hydroxyl radical attacking the sugar on the back bone of a DNA molecule
  38. 42. Oxidative DNA Damage <ul><li>Abstraction of H + atom from carbon atoms of sugar molecules </li></ul><ul><li>Disproportionations and rearrangement lead to C-C bond fragmentation and DNA strand break </li></ul>Sugar Moieties
  39. 43. Protein Oxidation <ul><li>Protein targets </li></ul><ul><ul><li>Receptors, transport proteins, enzymes, etc </li></ul></ul><ul><ul><li>Secondary damage – autoimmunity </li></ul></ul><ul><li>Protein oxidation products </li></ul><ul><ul><li>Protein carbonyl group, 3-nitrotyrosine, other oxidized amino acids </li></ul></ul><ul><li>Most susceptible amino acids </li></ul><ul><ul><li>Tyrosine, histidine, cysteine, methionine </li></ul></ul>
  40. 44. Protein Oxidation Oxidative protein degradations Modifications of amino acid chain Modifications of prosthetic group of enzymes Protein aggregation Protein fragmentation Activations of protease enzymes
  41. 45. Free Radical Toxicity
  42. 46. Free Radicals and Diseases <ul><li>Cancer </li></ul><ul><li>Inflammation/Infection </li></ul><ul><li>Ischemia-reperfusion injury </li></ul><ul><li>Neurodegenerative diseases </li></ul><ul><li>Cardiovascular diseases </li></ul><ul><li>Aging </li></ul><ul><li>Others (e.g., drug/chemical-induced toxicity, etc) </li></ul>
  43. 47. Ischemia-Reperfusion Injury <ul><li>Ischemic – reoxygenation </li></ul><ul><li>Tissue damages caused by excessive production of free radicals </li></ul><ul><li>Cells lose ability to pump sodium outward & develop intracellular edema </li></ul><ul><li>Organs function well after resuscitation but deteriorate in ensuing hours </li></ul>
  44. 48. Reasons for IRI <ul><li>Associated with the generation of ROS </li></ul><ul><li>Leukocyte sequestration & activation associated with generation of many inflammatory mediators such as TNF, PAF, & various proteases. </li></ul><ul><li>Disseminated intravascular coagulation </li></ul>
  45. 49. Ischemia-Reperfusion Injury ATP AMP Adenosine Hypoxanthine/Purine Xanthine dehydrogenase Xanthine oxidase REPERFUSION O 2 O 2 + H 2 O 2 OH - + Fe 2+ TISSUE INJURY i s c h e m i a Ca 2+ -dependent protease CO 2 pH TNF IL1 C5 O 2  - OH  Xanthine/Hypoxanthine O 2 .- + uric acid XOD O 2
  46. 50. Sources for reperfusion injury <ul><li>The catabolism of ATP to hypoxanthine </li></ul><ul><li>The activation of neutrophils </li></ul><ul><li>Ferrous form of iron catalyzing the conversion of SOR and H 2 o 2 to the hydroxyl radical </li></ul>
  47. 51. Sequelae <ul><li>Lipid peroxidation of cell & organelle membranes </li></ul><ul><li>Oxidize sulfhydryl groups </li></ul><ul><li>Activate or inactivate enzyme systems </li></ul><ul><ul><li>Impaired calcium transport </li></ul></ul><ul><ul><li>Decreased phosphocreatinine </li></ul></ul><ul><ul><li>Activated collagenases degrade basement membranes </li></ul></ul><ul><ul><li>Activated hyaluronidases degrade interstitial matrix </li></ul></ul><ul><ul><li>Myocardial contractility is impaired </li></ul></ul><ul><li>Cause DNA & RNA depolymerisation </li></ul>
  48. 52. Measurement of Oxidative Stress <ul><li>Oxygen consumption </li></ul><ul><li>Oxidative markers “footprints” </li></ul><ul><ul><li>Lipid peroxidation products (TBARs, lipid hydroperoxides, etc) </li></ul></ul><ul><ul><li>DNA hydroxylation products (8-OHGua, </li></ul></ul><ul><ul><li>Protein hydroxylation products (nitrosation products) </li></ul></ul><ul><li>Free radical detection </li></ul><ul><ul><li>Single photon counting </li></ul></ul><ul><ul><li>Chemiluminescence </li></ul></ul><ul><ul><li>Fluorescent probe </li></ul></ul><ul><ul><li>Electron paramagnetic resonance spectroscopy (EPR) </li></ul></ul>
  49. 53. ANTIOXIDANTS
  50. 54. Contents <ul><li>Oxidant-Antioxidant balance </li></ul><ul><li>Biological actions of antioxidant defense system </li></ul><ul><li>Antioxidant defense system </li></ul><ul><ul><li>Superoxide dismutase (SOD) </li></ul></ul><ul><ul><li>Catalase </li></ul></ul><ul><ul><li>Glutathione cycle/Glutathione peroxidase </li></ul></ul><ul><ul><li>Diet-derived antioxidants & Low molecular weight antioxidants </li></ul></ul><ul><li>Roles in the cellular protection against oxidative stress & oxidative stress-related diseases </li></ul>
  51. 55. Damage (Pro-oxidants) Defense (Antioxidants) Oxidant-Antioxidant Balance Damage (Pro-oxidants) Defense (Antioxidants) Decrease of antioxidant defense system Oxidative damage
  52. 56. Cellular Defense Mechanisms <ul><li>Isolation of generation sites of reactive oxygen species </li></ul><ul><li>Inhibition of propagation phase of reactive oxygen species </li></ul><ul><li>Scavenging of reactive oxygen species </li></ul><ul><li>Repair of the damage caused by reactive oxygen species </li></ul>
  53. 57. Protection Against ROS Damage <ul><li>Direct protection against ROS </li></ul><ul><ul><li>Superoxide dismutase, Glutathione peroxidase, Catalase </li></ul></ul><ul><li>Non-specific reduction system </li></ul><ul><ul><li>Glutathione, Vitamin C </li></ul></ul><ul><li>Protection against lipid peroxidation </li></ul><ul><ul><li>Glutathione peroxidase, Vitamin E,  -Carotene </li></ul></ul><ul><li>Sequestration of metals </li></ul><ul><ul><li>Transferrin, Lactoferrin, Ferritin, Metalothionein </li></ul></ul><ul><li>Repair systems </li></ul><ul><ul><li>DNA repair enzymes, Macroxyproteinases, Glutathione transferase </li></ul></ul>
  54. 58. Free radical scavenging systems
  55. 59. Antioxidant Defense System <ul><li>Antioxidant Enzymes </li></ul><ul><ul><li>Superoxide dismutase (SOD) </li></ul></ul><ul><ul><li>Catalase (CAT) </li></ul></ul><ul><ul><li>Glutathione peroxidase (GPx) </li></ul></ul><ul><li>Endogenous non-enzymatic antioxidants </li></ul><ul><ul><li>GSH, bilirubin </li></ul></ul>
  56. 60. Antioxidant Defense System <ul><li>Exogenous antioxidant molecules </li></ul><ul><ul><li> -Tocopherol -- prevents oxidation of fatty acids </li></ul></ul><ul><ul><li>Carotenoids (  -carotene, leutin, lycopene, etc) -- destroy a particularly damaging form of singlet oxygen </li></ul></ul><ul><ul><li>Ascorbic acid -- radical scavenging, recycling of vitamin E </li></ul></ul><ul><ul><li>Bioflavonoids -- potent antioxidant activity </li></ul></ul>
  57. 61. Superoxide Dismutase (SOD) Function k ~ 2-4 x 10 9 M -1 s -1 <ul><li>Only enzyme known to react with radical </li></ul><ul><li>The presence of SOD implies O2.- produced in </li></ul><ul><li>cell during normal metabolism </li></ul><ul><li>* SOD is a primary antioxidant enzyme </li></ul>2O 2 •- + 2H + H 2 O 2 + O 2
  58. 62. Intracellular Location of SOD <ul><li>CuZn-SOD </li></ul><ul><ul><li>Cytoplasm, nucleus, lysosomes </li></ul></ul><ul><li>Mn-SOD </li></ul><ul><ul><li>Mitochondrial matrix </li></ul></ul><ul><li>EC (CuZn) </li></ul><ul><ul><li>Plasma membrane, extracellular </li></ul></ul><ul><li>EC Mn-SOD </li></ul><ul><ul><li>Plasma membrane </li></ul></ul>
  59. 63. Structure and Properties of SOD <ul><li>CuZn-SOD </li></ul><ul><ul><li>One of the most stable protein </li></ul></ul><ul><ul><li>Inactivated by guanidine HCl, CN-, diethyldithiocarbamate (DETC) </li></ul></ul><ul><li>EC-SOD </li></ul><ul><ul><li>Inhibited by CN-, azide, H 2 O 2 , SDS </li></ul></ul><ul><ul><li>Located in extracellular fluids </li></ul></ul><ul><ul><li>Suppresses inflammation </li></ul></ul><ul><li>Fe/Mn-SOD </li></ul><ul><ul><li>Not stable </li></ul></ul>
  60. 64. Catalase (CAT) <ul><li>Function : Removes H 2 O 2 </li></ul><ul><li>2 H 2 O 2 2 H 2 O + O 2 </li></ul><ul><li>Prevents lipid peroxidation </li></ul><ul><li>and protein oxidation </li></ul>
  61. 65. Glutathione Cycle Glutathione ~ Glu-Cys-Gly Reduced glutathione (GSH) Oxidized glutathione (GSSG) Function : gets rid of H 2 O 2 or ROOH (hydroperoxide) ROOH ROH + H 2 O 2 GSH GSSG NADPH NADP Glutathione peroxidase Glutathione reductase
  62. 66. Glutathione Biosynthesis Two Step-Mechanism <ul><li>By enzyme Ɣ -glutamylcysteine synthetase </li></ul><ul><li>L-glutamate + L-cysteine + ATP L- Ɣ -glutamylcysteine +ADP + Pi </li></ul><ul><li>2. By enzyme glutathione synthetase </li></ul><ul><li>L- Ɣ -glutamylcysteine + glycine + ATP GSH + ADP + Pi </li></ul>Buthionine sulphoximine (BSO) inhibits Ɣ -glutamylcysteine synthetase Cellular GSH increase sensitivity to toxicants
  63. 67. Glutathione Peroxidase (GPx) Function : Removes H 2 O 2 & ROOH ROOH + 2 GSH ROH + H 2 O + GSSG Deficiency in GPX leads to oxidative hemolysis Protects against lipid peroxidation *Selenium*
  64. 69. Low Molecular Mass Agents <ul><li>Compounds synthesized in vivo </li></ul><ul><ul><li>bilirubin, melatonin, lipoic acid, uric acid, etc. </li></ul></ul><ul><li>Compounds derived from the diet </li></ul><ul><ul><li>Ascorbic acid </li></ul></ul><ul><ul><li>Vitamin E </li></ul></ul>
  65. 70. Melatonin <ul><li>Highly selective & electroactive endogenous indoleamine. </li></ul><ul><li>Present in good amounts in the nervous system. </li></ul><ul><li>Sacrificed & irreversibly oxidized. </li></ul><ul><li>Inhibit NOS </li></ul><ul><li>Stimulate brain GPX activity </li></ul><ul><li>Increases mRNA levels for Mn & Cu-Zn SOD </li></ul>
  66. 71. Ascorbic Acid <ul><li>Antioxidant Function </li></ul><ul><li>Donate 1 e- semidehydroascorbate (ascorbyl radical) </li></ul>Relatively unreactive
  67. 72. Tocopherol “ Chain-breaking antioxidant” Scavenges peroxyl radical Inhibits chain reaction of lipid peroxidation Eight naturally-occurring substances d-  -, d-  -, d-  - tocopherols d-  -, d-  -, d-  - tocotrienols
  68. 73. Biological Properties of Natural Antioxidants <ul><li>Natural antioxidants </li></ul><ul><ul><li>Polyphenols (phenolic, flavonoids), carotenoids, lycopene, etc </li></ul></ul><ul><li>Electron donor property </li></ul><ul><ul><li>Ability of antioxidant to donate an electron to a species (free radical) – reducing property </li></ul></ul><ul><ul><li>Antioxidant remains stable </li></ul></ul>
  69. 74. SUMMARY <ul><li>Characteristics of free radicals/reactive oxygen species </li></ul><ul><li>Endogenous/Exogenous formation of free radicals </li></ul><ul><li>Oxidative cell damage (lipids, DNA, proteins) </li></ul><ul><li>Oxidative damage-related carcinogenesis </li></ul><ul><li>Antioxidants (types, functions) </li></ul><ul><li>Antioxidant network </li></ul><ul><li>Roles in the preventions against oxidative damage </li></ul>
  70. 75. Bibliography <ul><li>Reactive Oxygen Species in Biological Systems-An Interdisciplinary Approach (Gilbert,2002). </li></ul><ul><li>Free-Radical-Induced DNA Damage and Its Repair - A Chemical Perspective (Springer, 2006) </li></ul><ul><li>Clinical Biochemistry of Domestic Animals (Sixth Edition) </li></ul><ul><li>Harpers Biochemistry 26 th ed </li></ul><ul><li>Lehninger's Principles of Biochemistry 4th Edition - D L Nelson, Cox Lehninger - W H Freeman 2004 </li></ul><ul><li>Textbook of Small Animal Surgery (Slatter) </li></ul>
  71. 76. Thank You ALL…

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