ANTIOXIDANTS ppt.pptx

this ppt about the antioxidants and their specific properties

1. ANTIOXIDANTS Dr.K.Sathishbabu Final year PG, KFMSR

2. Free radicals Antioxidants Types of Antioxidants Clinical significance Summary O utline 2

3. Free radicals Oxygen – highly reactive atom; capable of becoming part of potentially damaging molecule called “free radicals” Formed from oxidative reactions Damage the cells structurally & functionally Ex : Singlet oxygen (O 2 - ) , Superoxide anion (O 2 - ), Hydrogen peroxide (H 2 O 2 ), Hydroxyl radical (OH - ) & Hypochlorous acid (HCLO - ) 3

4. Free radical formation 4

5. Reactive oxygen species (ROS) Defined as all highly unstable and highly reactive oxygen containing molecules including free radicals Capable of reacting with membrane lipids, nucleic acids, proteins and enzymes resulting in cellular damage 5

6. Free radicals & ROS Oxygen-centered radicals: Superoxide O 2 - Hydroxyl OH - Sulphur -centered radical: Glutathione radical GS - Carbon-centered radical: Trichlormethyl (CCL 3 - ) Nitric oxide : NO - Reactive oxygen species (ROS): Oxygen-centered radicals O 2 - . OH - and Potentially dangerous non-radical derivatives of O 2 (H 2 O 2 , - O 2 , HOCI, and – O 3 ) 6

7. In vivo production of ROS & free radicals O 2 - and H 2 O 2 by Activated phagocytes Endothelial cells Fibroblasts and lymphocytes Auto oxidation reactions Leakage of electrons from the electron transport chains NO - by Vascular endothelial cells 7

8. Free radicals – physiological roles O2 - inactivates enzymes in bacteria in vitro, inactivates NADH dehydrogenase complex in the mitochondrial electron transport chain NO - (or a derivative) smooth muscle cell relaxation O2 - + NO -  peroxynitrite (ONOO - )  vasoconstriction (regulation of vascular tone) 8

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10. Free radicals - Sources 10

11. Mechanism of cell damage Endogenous sources : Mitochondrial leakage Respiratory burst Enzyme reaction etc. Environmental sources : Cigarette smoking UV Radiation/ Pollutants Xenobiotics etc Free radical formation Lipids Lipid per oxidation Membrane damage Proteins Oxidative modification of proteins Protein fragmentation / cross linkage DNA Single strand breakage / Base modification Altered gene expression CELL INJURY 11

12. Free radical measurement ORAC : Oxygen radical absorbance capacity TRAP : Total radical trapping antioxidant potential Beta carotene bleaching DPPH / Superoxide anion / NO / total phenol assays Measuring the serum samples & tissue homogenate of Lipid peroxidase (LPO) GSH / GR / GST SOD Catalase / LDH / G6P / CPK 12

13. Antioxidant - A molecule that prevents the breakdown of another molecule by oxygen - Slows or inhibits the oxidation reaction 13

14. Mechanism of antioxidant 14

15. MODES OF ACTION OF ANTIOXIDANT Chain breaking reactions Ex : α tocopherol which acts in lipid phase to trap the radical Reducing the concentration of reactive oxygen species Ex : glutathione Scavenging initiating radicals Ex : SOD which acts in aqueous phase to trap superoxide free radicals Chelating the transition metal catalysts 15

16. TYPES OF ANTIOXIDANTS 16

17. BASED ON PROPERTIES ENZYMATIC ANTIOXIDANTS Primary : Endogenous molecules Act at the source of ROS Continuous elimination Superoxide Dismutase(SOD), Catalase, Glutathione peroxidase 2. Secondary : -Exogenous molecules carried by food -Scavenge secondary free radicals -Glutathione reductase & Glucose-6-Phosphate Dehydrogenase 17

18. NON - ENZYMATIC ANTIOXIDANTS Vitamins : A,C & E Minerals : Zinc, Selenium, Manganese, Copper Carotenoids : B carotenes, Lycopene etc. Antioxidant co-factors : Co enzyme Q10 Low molecular weight Antioxidants : Glutathione, Uric acid Polyphenols : Flavonoids, Phenolic acids 18

19. BASED ON SOURCES Natural : Chlorophyll derivatives Carotenoids Essential oils Alkaloids & Phenolics Nitrogenic compounds Synthetic : Butylated hydroxyanisole Butylated hydroxytoluene Ethoxquin Propul gallate 19

20. BASED ON DEFENSE MECHANISM Preventive : Peroxidase Catalase Lactoferrin etc. Radical scavenging : Vitamin C Carotenoids Repair & Denovo Enzyme inhibitors 20

21. CLINICALLY IMPORTANT ANTIOXIDANTS 21

22. SUPEROXIDE DISMUTASE (SOD) Metalloprotein Ubiquitously in all aerobic organisms More potent antioxidant Mainly targets superoxide anion(O 2 - ) and singlet oxygen(‘O 2 ) Function : 2O 2 - + 2H + -------------------- H 2 O 2 + O 2 Has many subgroups : SOD1, SOD2 & SOD3 SOD 22

23. SOD - TYPES SOD 1 : Present in cytoplasm Co-factors : Cu & Zn Important constituent in apoptotic signaling & Oxidative stress Role in degenerative diseases, oldage and carcinogenesis SOD 2 : Present in mitochondria Co-factors : Fe & Mn Protects against cell death due to oxidative stress, ionizing radiation and inflammatory cytokines SOD 3 : Extracellular Elimination has only minimal effects Protects the brain, lungs and other tissues 23

24. GLUTATHIONE Mother of all antioxidants Hydrophilic ; found in every cells of the body “Directly found in cells and breakdown the free radicals within the cells” Scavenges hydroxyl free radicals Sources : Garlic, Broccoli, Onions, Dairy products, Oats, Chicken etc. 24

25. GLUTATHIONE Reduced form of glutathione : Regulates IL 2 dependent T lymphocyte proliferation Reduce oxidative stress Protects against cytotoxic effects of nicotine on fibroblasts Smoking – reduce glutathione in saliva & plasma Decrease the incidence of prostate, colon & lung cancer 25

26. VITAMINS - CAROTENES One of the essential antioxidant for health and well being Types : α , β , γ , δ – first two are most potent These are group of red, orange and yellow pigments found in plant foods(fruits and vegetables) β Carotenes : anti-ageing micronutrients, decrease the immune function, cardiac illnesses, cataract and cancer 26

27. VITAMINS - TOCOPHEROL Also known as “vitamin E” α -tocopherol is an active form Fat soluble ; present in all cell membranes Mainly stored in adipose tissue, liver and muscle Sources : Peanut oil, Sunflower oil, Cotton seed oil and Green leafy vegetables 27

28. VITAMINS - TOCOPHEROL Prevents per oxidation at cell membranes and protects poly unsaturated fats Enhances body’s immune responses Inhibits the conversion of nitrites into nitrosamines in stomach (Nitrosamines – cancer promoters) Lowers the risk of angina and cardiac disease mortality Slows the progression of Parkinson's disease 28

29. VITAMINS – ASCORBIC ACID Vitamin C Water soluble ; secondary free radical scavenger Present in extra cellular fluids Mainly neutralizes H 2 O 2 Sources : Citrus fruits - lime, orange, tomatoes, amla & cabbage, Watermelon etc. 29

30. VITAMINS – ASCORBIC ACID Protecting tissues against oxidative stress Suppresses the formation of carcinogens Reduce the risk of cardiovascular diseases by decreasing total cholesterol levels Maintains healthy collagen in skin, tissues and teeth etc. Reduced levels of vitamin C can cause cataract 30

31. MINERALS Works along with vitamins in fighting free radicals Ex : Vitamin E + Selenium  free radical scavenging Act as enzyme co-factors Zinc & Copper – for SOD1 & Iron & Mn – for SOD2 Selenium : reduces colorectal, prostate and lung cancers Zinc + vitamin A  synergistic action  persistent diarrhoea 31

32. PROTEINS Ceruloplasmin & Transferrin – prevents iron dependent lipid peroxidation Bilirubin – protects albumin bound free fatty acids from peroxidation Albumin – scavenges the free radicals which binds on its surface 32

33. HORMONES - MELATONIN Powerful antioxidant Can cross blood brain barrier and other cell membranes Binds with free radicals  forms stable complex  “Terminal / Suicidal antioxidant” 33

34. URIC ACID Most abundant ; Uncomplicated antioxidant Marker of oxidative stress More potent against singlet oxygen and hydroxyl radicals Sources : sweetbread, liver, beef meat etc. Reduce the risk of stroke, atherosclerosis and Parkinson’s disease. 34

35. ESSENTIAL OILS Volatile oils Isolated from various plant components – leaves, flower etc. Advantages : Small molecular size – easily penetrate skin tissues Lipid soluble – Easily penetrate & cross membranes Powerful antioxidant – prevent mutants and oxidants in cells 35

36. DRUGS WITH ANTIOXIDANT PROPERTY Xanthine oxidase inhibitors – Allopurinol, Oxypurinol N-acetyl cysteine MAO-B inhibitor : Selegiline Iron chelators – Deferoxamine Adenosine Statins – Atorvastatin Carvedilol 36

37. SUMMARY Oxidative reactions that releases the highly reactive free radicals that causes cell damage Antioxidants acts on free radicals and prevents cell damage Endogenous antioxidants focusing on primary free radicals Exogenous antioxidants obtained mainly from natural & dietary sources and targets secondary free radicals SOD – Continuous elimination within the cell level 37

38. SUMMARY Glutathione – mother of all antioxidants Fat soluble vitamins – present in membranes and prevents lipid peroxidation Water soluble vitamins – present in ECF and neutralizes H2O2 Minerals – act as enzyme co factors Melatonin – suicidal antioxidant Uric acid – most abundant & more potent against both 1&2’ ROS 38

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40. REFERENCES Sharma.H.L,Sharma.K.K.Principles of pharmacology.2 nd edition.Hyderabad: Parasmedical;2015 GOODMAN&GILMAN’S.The pharmacological basis of therapeutics.13 th edition.Mcgraw hill books;2017 Tripathi.K.D.Essentials of medical pharmacology.7 th edition.new delhi:Jaypee brothers;2013 Rituparna maiti.Postgraduate topics in pharmacology 2 nd edition.Hyderabad: PARAS; 2015. 40

41. THANK YOU 41