Antioxidants and their therapeutic implications
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  • 1. Antioxidants and their therapeutic implications Although oxygen is essential for life, excess oxygen can have harmful effects. When oxygen is metabolised by the body it creates substances called free radicals which cause damage to our cells. Free radicals can also be created by exposure to pollution, cigarette smoke and fatty foods.
  • 2. Excessive amounts of free radicals are thoughtto be related to the development of conditionssuch as:- Heart and liver disease Some cancers, Arthritis, Accelerated ageing Eyesight deterioration.
  • 3.  The body has its own natural defences against free radicals, but these systems can sometimes be overwhelmed. Antioxidants are naturally occurring nutrients in food or chemical compounds which help destroy free radicals and minimise damage to our cells. they can delay the start or slow the rate of lipid per oxidation reaction in food systems.
  • 4. SOURCES OF ANTIOXIDANTS  VITAMIN-E  VITAMIN-C  BETA-CAROTENE  SELENIUM  PHYTONUTRIENTS
  • 5. Vitamin E It is one of the strongest antioxidants, and can be found in nuts, oils, green vegetable and wholegrain. It helps prevent disease by destroying free radicals and protecting DNA in cells from damage.
  • 6. Vitamin C It has a dual role, in that it helps the body absorb vitamin E and protects it from harm. Citrus fruits and vegetables are the best food sources of vitamin C. Smokers in particular should ensure they get enough vitamin C, as it helps fight toxins and free radicals from cigarette smoke.
  • 7. Beta-carotene It is converted by the body into vitamin A. It benefits skin and hair, helps maintain strong bones and protects against eye problems. Beta-carotene is found mainly in red- and orange-coloured fruits and vegetable.
  • 8. Selenium It is the main mineral antioxidant. It is involved in the production of powerful enzymes which ‘mop up’ free radicals and deactivate them. Selenium is found in brazil nuts, seafood and red meat.
  • 9. Phytonutrients They are naturally occurring plant chemicals which don’t have any nutritional value, but which have the ability to act as antioxidants. Different types of phytochemical occur in different foods: flavonoids are found in abundance in fruit, vegetables, dark chocolate and red wine (which should be consumed in moderation); tea and grapes are a good source of polyphenols; allium sulphur compounds are found in onions, leeks and garlic.
  • 10. lipid per oxidation: Lipid per oxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes are formed resulting in cell damage.
  • 11. Mechanism of lipid peroxidation
  • 12. PROCESS INVOLVED IN THE MECHANISM OFLIPID PER OXIDATION  Initiation: Initiation is the step in which a fatty acid radical is produced. The most notable initiators in living cells are reactive oxygen species(ROS), such as OH· and HO2, which combines with a hydrogen atom to make water and a fatty acid radical.  Propagation: The fatty acid radical is not a very stable molecule, so it reacts readily with molecular oxygen, thereby creating a peroxyl fatty acid radical. This too is an unstable species that reacts with another free fatty acid, producing a different fatty acid radical and a lipid peroxide.
  • 13.  Termination: When a radical reacts with a non-radical, it always produces another radical, which is why the process is called a "chain reaction mechanism." The radical reaction stops when two radicals react and produce a non- radical species. Living organisms have evolved different molecules that speed up termination by catching free radicals and, therefore, protecting the cell membrane. One important such antioxidant is vitamin E. Other anti- oxidants made within the body include the enzymes superoxide dismutase, catalase, and peroxidase.
  • 14. EFFECTS OF LIPID PER OXIDATION:  Flavour Quality Loss:  Rancid flavour  Changes of colour and texture  Consumer Acceptance  Economic loss  Nutritional Quality Loss:  Essential Fatty Acids  Vitamins  Health Risks:  Toxic Compounds  Growth Retardation  Heart Diseases
  • 15. Ideal Antioxidants No harmful physiological effects Not contribute an objectionable flavor, odor, or color to the fat Effective in low concentration Fat-soluble Carry-through effect  No destruction during processing Readily-available Economical Not absorbable by the body
  • 16. Kinds of Antioxidants Natural antioxidants:  Tocopherols  Nordihydroguaretic Acid (NDGA)  Sesamol  Gossypol Synthetic antioxidants:  Butylated Hydroxy Anisole (BHA)  Butylated Hydroxy Toluene (BHT)  Propyl Gallate (PG)  Tertiary Butyl Hydroquinone (TBHQ)
  • 17. Therapeutic implications of antioxidants  Antioxidant in cardiovascular disease  Antioxidant therapy in cancer  Antioxidants in Brain injury:  Antioxidants in stroke treatment :  Antioxidants in neurodegenerative diseases  Antioxidants in apoptosis  Antioxidants in liver damage
  • 18. Antioxidant therapy in cardiovascular disease Antioxidant therapy may inhibit atherosclerosis and thereby prevent the clinical complications of the disease such as CAD, and in particular, MI. Free radicals are formed by several exogenous processes such as radiation and tobacco smoke, and are the endogenous natural by-products of cellular metabolism. these radicals tend to damage protein, DNA, lipids and carbohydrates as result cell death.
  • 19. Antioxidant therapy in cancerThe following is a list of common antioxidants used in cancer programs. Beta carotene Vitamin C Vitamin E Selenium Lipoic acid Poly MVA
  • 20. Beta caroteneBeta-carotene is a form of vitamin A. Vitamin Ais a strong immune booster. It stimulates theactivity of immune cells against tumor cells. Hasbeen shown to inhibit the promotion of caner,while beta carotene (precursor to vitamin A)inhibits the initiation of cancer. Beta-carotenecan decrease the amount of damage free radicalsdo to a cells DNA. Such DNA damage isthought to be one mechanism that causes cancer,and indeed, some early studies suggested thatbeta-carotene might reduce the risk of cancer.
  • 21. Vitamin CIt is known that vitamin C acts as an antioxidantand free radical scavenger that reacts directly withsuper oxide, hydroxyl radicals, and singlet oxygenproduced during normal cellular metabolism.Oxygen is necessary for life. Oxygen also comesin several radical forms that have been implicatedin both initiation and post initiation stages of thecarcinogenic process as well as in invasion andmetastatic processes. Aside from its antioxidantproperties, there is no single universal acceptedand proven explanation for vitamin Cs cancerfighting properties.
  • 22. Vitamin E Vitamin E is an important fat-soluble antioxidant, vitamin Es preventive role in cancer has been well proven. Highly malignant melanoma cell in vitro has been shown to be converted into differentiated (normal) cell after 3 days of exposure to Vitamin E succinate. Ovarian and cervical cancer - vitamin E slow downs the mitotic activity of cancer cell but normal cell dont get affected. Glioma tumor cells (present in the brain) are also more effective attacked by vitamin E succinate, probably because of its better penetration of blood bran barrier. Vitamin E succinate enhances radiation in cancer cell and protects the normal cell.
  • 23. Selenium It is a powerful antioxidant with a central role in the protection of tissues from the damaging effects of oxygen free radicals. The use of selenium compounds as a cancer treatment predates most conventional treatments currently in use. 200 mcg of selenium a day has been shown to reduce cancer death by 50% and prostate cancer by 62% after 4 years. Cancer patients are often found to be deficient in selenium. Selenium works synergistically with vitamin E.
  • 24. Lipoic acidIt is called the universal antioxidant for itsability to dissolve well in water and in fatenvironment, Lipoic acid increase theeffectiveness or potency in other antioxidants. Itcan cross the blood brain barrier while otherscannot .One of the most beneficial effects ofalpha Lipoic acid is its ability to regenerateother essential antioxidants such as vitamins Cand E, coenzyme, and glutathione.
  • 25. Poly MVA This is an alpha Lipoic acid complex with palladium. It is a non-toxic polynucleotide reductase named POLYDOX (USA trials), Poly-MVA (Canada and Mexico) or LAPd by some researchers. The element platinum is very lethal to cancer cells, but also very toxic to humans. Its close relative: palladium, however, is nontoxic in its present form. The MVA stands for minerals, vitamins, and amino acids. LAPd stands for Lipoic acid/Palladium complex.
  • 26. Antioxidants in Brain injury: Antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics, sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury.Antioxidants in stroke treatment : Experimental drug NXY-059 and ebselen are being applied in the treatment of stroke.
  • 27. Antioxidants in neurodegenerative diseases Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimers disease , Parkinsons disease, and amyotrophic lateral sclerosis.
  • 28. Others: These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. They may prevent damage to the liver caused by excessive alcohol.
  • 29. Submitted By: Manish Kumar M.Pharm Pharmacology Mangalayatan universityThank you