a review of oxidants, antioxidants and oxidative

8/2/2019 A Review of Oxidants, Antioxidants and Oxidative

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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

a review of oxidants, antioxidants and oxidative

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