A Review Of Oxidants, Antioxidants and Oxidative Stress

By : Jaka Susila

Presented In Seminar Akademis The Multiple Role of Antioxidants in the Improvement of Life Quality Fakultas Kedokteran Universitas Sebelas Maret Surakarta, Indonesia 2007 JS

Oxidants
History ; 1st reported by Fenton in 1894 In 1956 Denham Harman Oxidants/ Free radicals can Damage cells, mutagenesis, cancer and degeneration process

Oxidant
Electron Acceptors, substances that able to drag a pair of electron such as : ferri ion (Fe3+)
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Oxidants
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

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Oxidants
Types :
Reactive Oxygens Species
Superoksida O2Hidroksil OHPeroksil RO2 Hidroksiperoksil HO2-

Reactive Nitrogen Species

Nitrit oksida NO Nitrogen dioksida NO2-

Peroxynitrites
Superoxide anion + NO Peroxynitrit
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Free radicals are produced by:

1. Different processes e.g.areobic respiration (superoxide and hydroxy 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 new radicals.Example: lipid peroxidation (this is now accepted as central 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 cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins and Carbohydrat, Vascular tonic Signal Transduction Angiogenesis Defense system to microbe

Mutation Cancer Cardiovascular disease etc

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Immunomodulation

Antioxidants
History :
The term antioxidant (also "antioxygen") originally was used to refer specifically to a chemical that prevented the consumption of oxygen

Important for Industrial Procees such as corrosion, the vulcanization of rubber, and the polymerization of fuels.
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Antioxidants
Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity.

Vit A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in biochemistry of living organisms
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What are Antioxidants ?

antioxidant substance when present at low concentration delays or inhibit oxidation

removing radical intermediates, and inhibit other oxidation 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, within cell membrane, -tocopherol very effective in lipid core, disrupt lipid peroxidation. c. Extracellular enzim katalase, SOD, glutathione peroksidase,
glutathione, vitamin C, vitamin E, bilirubin, urate, albumin,

seruloplasmin, transferin, haptoglobin dan hemopexin

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CRITERIA FOR CONSIDERING IDEAL ANTIOXIDANTS

SPECIFICITY OF FREE RADICAL QUENCHING METAL CHELATING ACITIVITY INTERACTION WITH OTHER ANTIOXIDANTS EFFECTS ON GENE EXPRESSION ABSORPTION AND BIOAVAILABILITY CONCENTRATION IN TISSUES, CELLS, AND EXTRACELLULAR FLUID LOCATION (IN AQUEOUS OR MEMBRANE DOMAINS OR 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 the pathogenesis 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 AND PYRIDINE NUCLEOTIDES IMPAIRMENT OF SIGNAL TRANDUCTION AND ION HOMEOSTATIS MODIFICATION OF CYTOSCELETAL ORGANIZATION INHIBITION OF GLYCOLISIS INFLICTION OF DNA DAMAGE COLLAPSE OF THE MITOCHONDRIAL POTENTIAL ATP 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 disease symptoms

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Reactive Oxygen Species (ROS) Production and Disruption of Cellular Homeostasis

Endogenous sources of ROS Exogenous sources of ROS Radiation (Ultraviolet, etc) Ozone Hyperoxia Xenobiotics

Mitochondria Cytochrome p450 Peroxisomes Inflammatory cells

Antioxidants
Enzymatic (SOD, CAT, GSHperox) Nonenzymatic (Vit. E, GSH, Vit. C)

Oxidative damage
(Lipid, DNA, protein)
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Summary 1
1.

2.

3.

Free Radicals is Any chemical species that contains unpaired electron. Unpaired electron increase the chemical reactivity of an atom or molecule antioxidant substance when present at low concentration delays or inhibit oxidation, before they can damage cells Oxidative stress is defined as Disturbance in the balance between the production of reactive oxygen species ( 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 as aging, cancer, and cardiovascular, neuromuscular, and joint disease 5. It is unclear if oxidants trigger the disease, or if they are produced as a consequence of the disease and cause the disease symptoms

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Terima Kasih

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