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A Review Of Oxidants, Antioxidants andOxidative Stress
By :
Jaka Susila
Presented In Seminar Akademis The Multiple Role ofAntioxidants in the Improvement of Life Quality
Fakultas Kedokteran Universitas Sebelas Maret
Surakarta, Indonesia
2007
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Oxidants
History ;
1st reported by Fenton in 1894
In 1956 Denham Harman Oxidants/ Free radicalscan Damage cells, mutagenesis, cancer anddegeneration process
OxidantElectron Acceptors, substances that able to drag a pair ofelectron such as : ferri ion (Fe3+)
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What are the free radicals ?
Any chemical species that contains unpaired electron.Unpaired electron increase the chemical reactivity
of an atom or molecule.
Highly reactivity (unstable)
Chain reaction New radicals
Oxidants
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Oxidants
Reactive Oxygens SpeciesSuperoksida O2-Hidroksil OH-Peroksil RO2Hidroksiperoksil HO2-Reactive Nitrogen SpeciesNitrit oksida NONitrogen dioksida NO2-PeroxynitritesSuperoxide anion + NO Peroxynitrit
Types :
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Free radicals are produced by:
1. Different processes e.g.areobic respiration (superoxide andhydroxy radical)
2. production of superoxide and hypochlotrous acid (phagocytes)
3. activated phagocytes
4. water by electromagnetic radiation ( hydroxy radical)5. reaction of radical with non radical(macromolecules, lipid,
nucleic acid CHO as target) produce fr-chain reaction newradicals.Example: lipid peroxidation (this is now accepted ascentral for the process of atherosclerosis)
6. Oxidation of catecholamines, activation of arachidonic acid
7. Many others recently known
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Overview jalur respiratori mitokondria dan tahap-tahap yang berkontribusi dalam
pembentukan ROS
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Role of Free radicals
oxidants can damage cellsby starting chemical chain
reactions such as lipidperoxidation, or by
oxidizing DNA or proteinsand Carbohydrat,
Mutation
Cancer
Cardiovascular disease
etc
Vascular tonic
Signal Transduction
Angiogenesis
Defense system tomicrobe
Immunomodulation
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Antioxidants
The term antioxidant (also "antioxygen") originally wasused to refer specifically to a chemical that
prevented the consumption of oxygen
Important for Industrial Procees such ascorrosion, the vulcanization of rubber, and the
polymerization of fuels.
History :
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Antioxidants
Early research on the role of antioxidants in biology
focused on their use in preventing the oxidation ofunsaturated fats, which is the cause of rancidity.
Vit A, C, and E as antioxidants that
revolutionized the field and led to the realizationof the importance of antioxidants in
biochemistry of living organisms
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What are Antioxidants ?
antioxidant substance when present at lowconcentration delays or inhibit oxidation
removing radical intermediates, and inhibit otheroxidation reactions by being oxidized themselves
before they can damage cells
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Tissue defenses againts radical attack
a. Cellular (Water-Soluble): Dismutase (SOD Zn/Cu cytosol,SOD Mn mitochondria), Peroxidase (Glutathion
peroxidase), Catalase ( in []c removes 2 H2O2
b. Membrane (Fat-soluble) : vit E, -carotene, Co-Q, withincell membrane, -tocopherol very effective in lipid core,disrupt lipid peroxidation.
c. Extracellularenzim katalase, SOD, glutathione peroksidase,glutathione, vitamin C, vitamin E, bilirubin, urate, albumin,
seruloplasmin, transferin, haptoglobin dan hemopexin
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CRITERIA FOR CONSIDERINGIDEAL ANTIOXIDANTS
SPECIFICITY OF FREE RADICAL QUENCHING
METAL CHELATING ACITIVITY
INTERACTION WITH OTHER ANTIOXIDANTS
EFFECTS ON GENE EXPRESSIONABSORPTION AND BIOAVAILABILITY
CONCENTRATION IN TISSUES, CELLS, ANDEXTRACELLULAR FLUID
LOCATION (IN AQUEOUS OR MEMBRANE DOMAINSOR IN BOTH?)
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What is oxidative stress?
Disturbance in the balance between the production of
reactive oxygen species ( free radicals) and
antioxidant defenses.
Oxidative stress has been associated with thepathogenesis of many human diseases, such as
aging, cancer, and cardiovascular,neuromuscular, and joint disease.
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MECHANISM OF OXIDATIVE CELL DAMAGE
OXIDATION OF INTRACELLULAR THIOLS ANDPYRIDINE NUCLEOTIDES
IMPAIRMENT OF SIGNAL TRANDUCTION AND IONHOMEOSTATIS
MODIFICATION OF CYTOSCELETALORGANIZATION
INHIBITION OF GLYCOLISIS
INFLICTION OF DNA DAMAGE
COLLAPSE OF THE MITOCHONDRIAL POTENTIALATP DEPLETION
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Oxidative Stress vs Disease
It is unclear if oxidants trigger the disease,or if they are produced as a consequence
of the disease and cause the diseasesymptoms
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Reactive Oxygen Species (ROS) Productionand Disruption of Cellular Homeostasis
Endogenous sourcesof ROS
Exogenous sourcesof ROS
Radiation (Ultraviolet, etc) Ozone Hyperoxia
Xenobiotics
Mitochondria Cytochrome p450 Peroxisomes Inflammatory cells
Enzymatic
(SOD, CAT, GSHperox) Nonenzymatic
(Vit. E, GSH, Vit. C)
Antioxidants
Oxidative damage(Lipid, DNA, protein)
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Summary 1
1. Free Radicals is Any chemical species that
contains unpaired electron. Unpaired electronincrease the chemical reactivity of an atom ormolecule
2. antioxidant substance when present at lowconcentration delays or inhibit oxidation, beforethey can damage cells
3. Oxidative stress is defined as Disturbance in the
balance between the production of reactive oxygenspecies ( free radicals) and antioxidant defenses
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Summary 2
4. Oxidative stress has been associated with the
pathogenesis of many human diseases, such asaging, cancer, and cardiovascular, neuromuscular,and joint disease
5. It is unclear if oxidants trigger the disease, or if theyare produced as a consequence of the disease andcause the disease symptoms
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Terima Kasih