Transcript
Page 1: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

GENERATION OF FREE GENERATION OF FREE RADICALS, OXIDATIVE STRESS RADICALS, OXIDATIVE STRESS

AND THEIR DAMAGING AND THEIR DAMAGING PROPERTIESPROPERTIES

āļĻāļĻ . . āđ€āļāļĩïŋ―āļĒāļĢāļ•āļīāļ„āļļïŋ―āļ“ āđ€āļāļĩïŋ―āļĒāļĢāļ•āļīāļ„āļļïŋ―āļ“ āļ”āļĢāļ”āļĢ . . āđ„āļĄāļ•āļīāļĢïŋ― āļŠāļļïŋ―āļ—āļ˜āđ„āļĄāļ•āļīāļĢïŋ― āļŠāļļïŋ―āļ—āļ˜āļˆāļīāļ•āļīāļ•āļīïŋ―āļˆāļīāļ•āļīāļ•āļīïŋ―

E-mail: E-mail: [email protected]@chiangmai.ac.th

Page 2: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļŦāļąïŋ―āļ§āļ‚āđ‰ïŋ―āļ­āļšāļĢāļĢāļĒāļēāļĒāļŦāļąïŋ―āļ§āļ‚āđ‰ïŋ―āļ­āļšāļĢāļĢāļĒāļēāļĒ

1.1. āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ„āļļ!āļ­āļ­āļ°āđ„āļĢāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ„āļļ!āļ­āļ­āļ°āđ„āļĢ??2.2. āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ€āļāļĩāļ”āđ„āļ”ïŋ―āļ­āļĒ"āļēāļ‡āđ„āļĢāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ€āļāļĩāļ”āđ„āļ”ïŋ―āļ­āļĒ"āļēāļ‡āđ„āļĢ?? 3. 3. āļŠāļļāļĄāļšïŋ―āļ•āļīāļ‚āđ‰āļ­āļ‡āļŠāļļāļĄāļšïŋ―āļ•āļīāļ‚āđ‰āļ­āļ‡āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ•āļī"āļ­āļŠāļļïŋ―āļ‚āđ‰āļ āļēāļžāđāļĨāļ°āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ•āļī"āļ­āļŠāļļïŋ―āļ‚āđ‰āļ āļēāļžāđāļĨāļ°āļŠāļĩïŋ―āļ§āļ•āļīāļŠāļĩïŋ―āļ§āļ•āļī 4. Oxidative stress and 4. Oxidative stress and healthhealth 5.5. Damaging properties of free Damaging properties of free radicalsradicals

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āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļŠāļļāļēāļĢāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° (free radical)

āđ€āļ›āđ‡)āļ™āļļāļ­āļ°āļ•āļīāļ­āļĄāļŦāļąāļĢ!āļ­āļāļĩāļĨïŋ―"āļĄāļ‚āđ‰āļ­āļ‡āļ­āļ°āļ•āļīāļ­āļĄāļ—ïŋ―*āļĄïŋ―āļŦāļąāļ™āļļ+*āļ‡āļŦāļąāļĢ!āļ­āļĄāļēāļāļĩāļāļĩāļ§"āļēāļŦāļąāļ™āļļ+*āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļ—ïŋ―*āđ„āļĄ"āđ„āļ”ïŋ―āļˆāļīïŋ―āļšāļ„āļļïŋ―" (unpaired electron) āļĄïŋ―āļ„āļļāļ§āļēāļĄāđ„āļĄ"āđ€āļŠāļļāļ–āļĩïŋ―āļĒāļĢ (unstable) āļ§"āļ­āļ‡āđ„āļ§āļĄāļēāļāļĩ (reactive) āđƒāļ™āļļāđ€āļ™āļļ!.āļ­āđ€āļĒ!*āļ­āļŠāļļïŋ―āļ•āļīāļ§ïŋ―

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļŠāļļāļēāļĄāļēāļĢāļ–āļĩāļ—/āļēāļĨāļēāļĒāđ€āļ‹āļĨāļĨïŋ― āļ—/āļēāđƒāļŦāļąïŋ―āđ‚āļĢāļ„āļļāđ€āļ›āđ‡)āļ™āļļāļĄāļēāļāļĩāļ‚āđ‰+.āļ™āļļ āđ€āļŠāļĩ"āļ™āļļ āđ‚āļĢāļ„āļļāļĄāļ°āđ€āļĢ2āļ‡ āđ‚āļĢāļ„āļļāļŦāļąïŋ―āļ§āđƒāļˆāļīāđāļĨāļ°āļŦāļąāļĨāļ­āļ”āđ€āļĨ!āļ­āļ” āđāļĨāļ°āđ‚āļĢāļ„āļļāļ­!*āļ™āļļ āļ—ïŋ―*āđ€āļāļĩïŋ―*āļĒāļ§āļ‚āđ‰ïŋ―āļ­āļ‡āļāļĩïŋ―āļšāļāļĩāļēāļĢāđ€āļŠāļļ!*āļ­āļĄāļŦāļąāļĢ!āļ­āļŠāļĩāļĢāļēāļ āļēāļž

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āļ­āļ°āļ•āļīāļ­āļĄāđāļĨāļ°āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ­āļ°āļ•āļīāļ­āļĄāđāļĨāļ°āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°1. āļ•āļīāļēāļĄāļŦāļąāļĨïŋ―āļāļĩāļāļĩāļēāļĢāļ‚āđ‰āļ­āļ‡quantum mechanics āđƒāļ™āļļāļ—ïŋ―āļāļĩāđ†āļ­āļ°āļ•āļīāļ­āļĄ āļĄïŋ―āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļ­āļĒïŋ―"āđƒāļ™āļļāđ€āļŠāļĩāļĨāļĨïŋ― (shells) āļŦāļąāļĢ!āļ­āļ­āļ­āļĢïŋ―āļšāļ— (orbits) āļĢāļ­āļšāļ™āļļāļ§āđ€āļ„āļļāļĨïŋ―āļĒāļŠāļļ 2.āđƒāļ™āļļāđāļ•āļī"āļĨāļ°āļ­āļ­āļĢïŋ―āļšāļ—āļĄïŋ―āļŠāļļïŋ―āļšāļ­āļ­āļĢïŋ―āļšāļ— (sub-orbits) āđ€āļĢïŋ―āļĒāļāļĩāļ§"āļēāļ­āļ­āļĢïŋ―āļšāļ—ïŋ―āļĨ (orbitals) 3. āđƒāļ™āļļāđāļ•āļī"āļĨāļ°āļ­āļ­āļĢïŋ―āļšāļ—ïŋ―āļĨāđ€āļ›āđ‡)āļ™āļļāļ—ïŋ―*āļ­āļĒïŋ―"āļ‚āđ‰āļ­āļ‡āļŠāļļāļ­āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļ 4. āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ€āļāļĩāļ”āļ‚āđ‰+.āļ™āļļāđ€āļĄ!*āļ­āđƒāļ™āļļāļ­āļ­āļĢïŋ―āļšāļ—ïŋ―āļĨāļĄïŋ―āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāđ€āļāļĩāļ™āļļāļŦāļąāļĢ!āļ­āļ‚āđ‰āļēāļ”āđ„āļ›āđ‡āļŦāļąāļ™āļļ+*āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļ

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āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļĄïŋ―āļŠāļļāļ­āļ‡āđāļšāļš āļŦāļąāļĢ!āļ­āļŠāļļāļ­āļ‡ spin

1.āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļĄïŋ―āļĨïŋ―āļāļĩāļĐāļ“āļ°āđ€āļ›āđ‡)āļ™āļļāļ„āļļāļĨ!*āļ™āļļ āļĄïŋ―āļāļĩāļēāļĢāđ€āļ„āļļāļĨ!*āļ­āļ™āļļāļ—ïŋ―*āđƒāļ™āļļāļŠāļļāļ™āļļāļēāļĄāđāļĄ"āđ€āļŦāļąāļĨ2āļāļĩ āļāļĩāļēāļĢāđ€āļ„āļļāļĨ!*āļ­āļ™āļļāļ—ïŋ―*āļ‚āđ‰āļ­āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļ­āļēāļˆāļīāđ€āļ›āđ‡)āļ™āļļāđƒāļ™āļļāļĨïŋ―āļāļĩāļĐāļ“āļ°āļ•āļīāļēāļĄāđ€āļ‚āđ‰2āļĄāļ™āļļāļēāļŽāļīāļāļĩāļēāļŦāļąāļĢ!āļ­āļ—āļ§āļ™āļļāđ€āļ‚āđ‰2āļĄāļ™āļļāļēāļŽāļīāļāļĩāļē (spin up āļŦāļąāļĢ!āļ­ spin down)2.āđƒāļ™āļļāļŦāļąāļ™āļļ+*āļ‡āļ­āļ­āļĢïŋ―āļšāļ—ïŋ―āļĨāļŠāļļāļ­āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāđ„āļĄ"āļŠāļļāļēāļĄāļēāļĢāļ–āļĩāđ€āļ„āļļāļĨ!*āļ­āļ™āļļāļ—ïŋ―*āđƒāļ™āļļāļ—āļĻāļ—āļēāļ‡āđ€āļ”ïŋ―āļĒāļ§āļāļĩïŋ―āļ™āļļāđ„āļ”ïŋ― 3. āđƒāļ™āļļāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļŦāļąāļ™āļļ+*āļ‡āļ•āļīïŋ―āļ§āđƒāļ™āļļāļ­āļ­āļĢïŋ―āļšāļ—ïŋ―āļĨāļ•āļīïŋ―āļ­āļ‡āļāļĩāļēāļĢāļ­ïŋ―āļāļĩāļŦāļąāļ™āļļ+*āļ‡āļ­āđ€āļĨāļ„āļļāļ•āļīāļĢāļ­āļ™āļļāļ—ïŋ―*āļĄïŋ―āļ—āļĻāļ—āļēāļ‡āļ•āļīāļĢāļ‡āļ‚āđ‰ïŋ―āļēāļĄāļĄāļēāđ€āļ‚āđ‰ïŋ―āļēāļ„āļļïŋ―"

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Free radicals are the most active species in the reaction process, and are characterized by unpaired electrons.

Free radicals are electrically neutral, which distinguish them from the ions that are electrically charged (electrons/protons unbalance)! 

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PROPERTIES OF PROPERTIES OF FREE FREERADiCALSRADiCALS

- - CChemical processes hemical processes oror combustioncombustion-Consist of a chain of reactions in two -Consist of a chain of reactions in two ways:ways:1. based on 1. based on products and reactantsproducts and reactants..2. based on radicals (initiating, 2. based on radicals (initiating, branching, propagating, terminating).branching, propagating, terminating).  

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āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļŦāļąāļĨāļēāļĒāļŠāļĩāļ™āļļāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļŦāļąāļĨāļēāļĒāļŠāļĩāļ™āļļāļ”-āļŠāļļāļēāļĢāļ›āđ‡āļĢāļ°āļāļĩāļ­āļšāļ­āļ­āļāļĩāļ‹āđ€āļˆāļīāļ™āļļ āļŦāļąāļĢ!āļ­ āđ„āļ™āļļāđ‚āļ•āļīāļĢāđ€āļˆāļīāļ™āļļ āļŦāļąāļĢ!āļ­āļ„āļļāļĨāļ­āļĢïŋ―āļ™āļļāļ‹+*āļ‡āļŠāļļāļēāļĄāļēāļĢāļ–āļĩāđ€āļ›āđ‡)āļ™āļļāļŠāļļāļēāļĢāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° - āļŠāļļ"āļ§āļ™āļļāđƒāļŦāļąāļāđˆ"āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļāļĩāđ€āļ›āđ‡)āļ™āļļāļŠāļļāļēāļĢāļ›āđ‡āļĢāļ°āļāļĩāļ­āļšāļ­āļ­āļāļĩāļ‹āđ€āļˆāļīāļ™āļļ

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āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° āļŠāļ™āļīïŋ―āļ”āļ•āđˆïŋ―āļēāļ‡ āđ†

-āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ‹ïŋ―āđ€āļ›āđ‡āļ­āļĢïŋ―āļ­āļ­āļāļĩāđ„āļ‹āļ”ïŋ― (O2.-)

- āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ„āļŪāļ”āļĢāļ­āļāļĩāļ‹ïŋ― (OH.) - āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāđ„āļ‚āđ‰āļĄïŋ―āļ™āļļāđ€āļ›āđ‡āļ­āļĢïŋ―āļ­āļ­āļāļĩāļ‹ïŋ― (LOOH.) - āļ‹āļ‡āđ€āļāļĩāļĨ2āļ—āļ­āļ­āļāļĩāļ‹āđ€āļˆāļīāļ™āļļ (O.) - āđ„āļŪāđ‚āļ”āļĢāđ€āļˆāļīāļ™āļļāđ€āļ›āđ‡āļ­āļĢïŋ―āļ­āļ­āļāļĩāđ„āļ‹āļ”ïŋ― (H2O2) - āļāļĩāļĢāļ”āđ„āļŪāđ‚āļ›āđ‡āļ„āļļāļĨāļ­āļĢïŋ―āļŠāļļ (HClO) - āđ„āļ™āļļāļ•āļīāļĢāļ„āļļāļ­āļ­āļāļĩāđ„āļ‹āļ”ïŋ― (NO)

REACTIVE OXYGEN SPECIES

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Enzymatic or non-enzymatic reactionsFruit browningBurningsEnginesPhotooxidationRadiationsOzoneEtc.

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ€āļāļĩāļ”āļ‚āđ‰+.āļ™āļļāļ āļēāļĒāļ™āļļāļ­āļāļĩāļĢ"āļēāļ‡āļāļĩāļēāļĒ

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āļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āđ„āļŦāļąāļĄïŋ―

O2 + M  O* + O* + M

          CH4 + O*     OH* + CH3*          CH3* + O2     O* + CH3O*         CH3* + O2     OH* + CH2O---------------------------------------------------------------------- CH4 + O2 CO2 + H2O 

* Free radicals

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Mechanism of Free Radicals by Metal Ions

HABER-WEISS REACTIONThe generation of hydroxyl radicals

O.2 + Fe+++-----> O

2 + Fe + +

H2O2 + Fe++--> OH. + OH- + Fe+

++

O.2 + H2O2 ---> O

2 + OH

. + OH-

Page 13: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ― āļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āļ—/āļēāđ„āļŦāļąïŋ―āđ€āļāļĩāļ”āļĄāļĨāļ āļēāļ§āļ°āļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āļ—/āļēāđ„āļŦāļąïŋ―āđ€āļāļĩāļ”āļĄāļĨāļ āļēāļ§āļ°

Page 14: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđāļĨāļ°āļŠāļļāļēāļĢāļĄāļĨāļžāļĐ āļ•āļī"āļēāļ‡ āđ† āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āļ‚āđ‰āļ­āļ‡āđ€āļ„āļļāļĢ!*āļ­āļ‡āļĒāļ™āļļāļ•āļīïŋ― āļ•āļī"āļ­āļ§ïŋ―āļ™āļļ āļāļĩāļēāļĢāđ€āļāļĩāļ”āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđāļĨāļ°āļŠāļļāļēāļĢāļĄāļĨāļžāļĐ āļ•āļī"āļēāļ‡ āđ† āļˆāļīāļēāļāļĩāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ―āļ‚āđ‰āļ­āļ‡āđ€āļ„āļļāļĢ!*āļ­āļ‡āļĒāļ™āļļāļ•āļīïŋ― āļ•āļī"āļ­āļ§ïŋ―āļ™āļļ

Generalized Reaction Scheme for Photochemical Smog Formation

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āļāļĩāļēāļĢāđ€āļāļĩāļ”āļŠāļļāļēāļĢāļ•āļī"āļēāļ‡ āđ† āđƒāļ™āļļāļ›āđ‡āļāļīāļāļĩāļĢāļĒāļēāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ― āļāļĩāļēāļĢāđ€āļāļĩāļ”āļŠāļļāļēāļĢāļ•āļī"āļēāļ‡ āđ† āđƒāļ™āļļāļ›āđ‡āļāļīāļāļĩāļĢāļĒāļēāļāļĩāļēāļĢāđ€āļœāļēāđ„āļŦāļąāļĄïŋ― 1) Nitrogen oxides generate oxygen atoms 2 ) Oxygen atoms form hydroxyl radicals 3 ) Hydroxyl radicals generate hydrocarbon

radicals 4 ) Hydrocarbon radicals form hydrocarbon

peroxides 5 ) Hydrocarbon peroxides form aldehydes 6 ) Aldehydes form aldehyde peroxides 7 ) Aldehyde peroxides form

peroxyacylnitrates

Page 16: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

-āļ™āļļāļ§āđ€āļ„āļļāļĨïŋ―āļĒāļŠāļļāļ—ïŋ―*āļ­āļĒïŋ―"āļ‚āđ‰āļ­āļ‡āļ”ïŋ―āđ€āļ­2āļ™āļļāđ€āļ­ ( DNA) -āđ„āļĄāđ‚āļ•āļīāļ„āļļāļ­āļ™āļļāđ€āļ”āļĢïŋ―āļĒ (mitochondria) -āļāļĩāļ­āļĨāđ„āļˆāļī (Golgi apparatus) - āđ„āļĢāđ‚āļšāđ‚āļ‹āļĄ (ribosome) - āđ„āļ‹āđ‚āļ•āļīāļ‹āļ­āļĨ-āđ„āļĨāđ‚āļ‹āđ‚āļ‹āļĄ (lysosome)

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ€āļāļĩāļ”āļ‚āđ‰+.āļ™āļļāļ āļēāļĒāđƒāļ™āļļāđ€āļ‹āļĨāļĨïŋ―

Page 17: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ āļēāļĒāđƒāļ™āļļāđ€āļ‹āļĨāļĨïŋ―

Page 18: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ āļēāļĒāđƒāļ™āļļ Mitochondria

Page 19: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

F - ree radicals and excited statespecies

A key role in both normal biological function and in the pathogenesis

M icrobiocidal mechanismI nflammatory responseT oxicity of many drugsAging C arcinogenesis.C ertain diseases: ocular,

neurological, psychiatric

Page 20: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

Formation of Free Radicals:Redox Formation of Free Radicals:Redox reactions (Reduction-oxidation)reactions (Reduction-oxidation)

Reactions with exchange of electrons Reactions with exchange of electrons between reactantsbetween reactantsReduction is the gain of electronsReduction is the gain of electrons

R + e- R-R + e- R- Oxidation is the loss of electronsOxidation is the loss of electrons

R- R + e-  R- R + e-  FeFe2+ Fe Fe 3+ + e- + e-  e.g. electric energy, electrochemical e.g. electric energy, electrochemical cells, batteries, cells, batteries,

Page 21: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

Peroxidation of Free RadicalsOn Polyunsaturated Lipid (LH)

L. = Lipid alkyl radical

LOO . = Lipid peroxyl radical LL = Polymerized lipids

OH. + LH ---> H2O + L.

L . + O2 ---> LOO .

LOO . + H2O ---> LOOH + L.

L . + L. ---> LL

Page 22: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ āļēāļĒāđƒāļ™āļļāđ€āļ‹āļĨāļĨïŋ― -Mitochondria

Mitochondria: source and target of free radical species.

Page 23: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļāļĩāļēāļĢāļ—/āļēāļĨāļēāļĒāļ‚āđ‰āļ­āļ‡āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ āļēāļĒāđƒāļ™āļļ āđ€āļ‹āļĨāļĨïŋ―

Page 24: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļāļĩāļēāļĢāļ›āđ‡;āļ­āļ‡āļāļĩïŋ―āļ™āļļāļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āđ‚āļ”āļĒāđ€āļ­āļ™āļļāđ„āļ‹āļĄïŋ―

Page 25: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

Oxidative damage of LDL molecule

Page 26: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

Gene Damage and Repair in Aging

āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° āļŠāļļāļēāļĢāļžāļĐ āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° āļŠāļļāļēāļĢāļžāļĐ āļŠāļļāļēāļĢāļāļĩ"āļ­āļāļĩāļĨāļēāļĒāļžïŋ―āļ™āļļāļ˜ïŋ―ïŋ― āļŠāļļāļēāļĢāļāļĩ"āļ­āļāļĩāļĨāļēāļĒāļžïŋ―āļ™āļļāļ˜ïŋ―ïŋ―

āļĄāļ°āđ€āļĢ2āļ‡āļĄāļ°āđ€āļĢ2āļ‡

Page 27: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

(OXIDATIVE DAMAGE AND DISEASES

āđāļŦāļąāļĨ"āļ‡āļ‚āđ‰āļ­āļ‡āļžāļĐāļ­āļ­āļāļĩāļ‹āđ€āļ”āļŠāļĩïŋ―āļ™āļļ

- āđ€āļĄāļ•āļīāļ°āļšāļ­āļĨāļŠāļļāļĄïŋ― āđƒāļ™āļļāđ„āļĄāđ‚āļ•āļīāļ„āļļāļ­āļ™āļļāđ€āļ”āļĢïŋ―āļĒ-āļŠāļļāļēāļĢāļžāļĐ āļ„āļļāļ§ïŋ―āļ™āļļāđ„āļŸ āļŠāļļāļēāļĢāđ€āļ„āļļāļĄïŋ―-āļĢïŋ―āļ‡āļŠāļļïŋ― - -UV, X ray, -ray- āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ° (oxidative stress)- reactive

oxygen species(ROS)--āđ„āļŪāđ‚āļ”āļĢāđ€āļˆāļīāļ™āļļāđ€āļ›āđ‡āļ­āļĢïŋ―āļ­āļ­āļāļĩāđ„āļ‹āļ”ïŋ―- āļ­āļ­āļ­āļ™āļļāļ­āļŠāļļāļĢāļ°- āļ—āļ­āļ‡āđāļ”āļ‡, āđ€āļŦāļąāļĨ2āļāļĩ

āđ‚āļĢāļ„āļļāļ—ïŋ―*āđ€āļāļĩāļ”āļ‚āđ‰+.āļ™āļļ- āđ‚āļĢāļ„āļļāļŦāļąïŋ―āļ§āđƒāļˆāļī āđ€āļŠāļļïŋ―āļ™āļļāļ•āļīïŋ―āļšāļ•āļīïŋ―āļ™āļļ- āđ‚āļĢāļ„āļļāļŦāļąāļĨāļ­āļ”āđ€āļĨ!āļ­āļ”āđāļ‚āđ‰2āļ‡āļ•āļīïŋ―āļ§- āđ‚āļĢāļ„āļļāļĄāļ°āđ€āļĢ2āļ‡- āđ‚āļĢāļ„āļļāđ„āļ‚āđ‰āļ‚āđ‰ïŋ―āļ­āļ­ïŋ―āļāļĩāđ€āļŠāļļāļš- āđ‚āļĢāļ„āļļāđ€āļŠāļļ!*āļ­āļĄāļŠāļļāļ āļēāļž -Alzheimer’s disease- āđ‚āļĢāļ„āļļāđ€āļšāļēāļŦāļąāļ§āļēāļ™āļļ- āļ•āļīïŋ―āļ­āļāļĩāļĢāļ°āļˆāļīāļāļĩāļ•āļīāļē- āļŠāļĩāļĢāļēāļ āļēāļž--

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Aging: Balance of Free Radicals and Antioxidants

â€Ē Can You Live to Be 120 Years Old?

Page 29: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

Genetic Responses to FreeRadicals

Homeostasis and Gene ControlGene regulation mechanisms have evolved allowing cells to fine-tune the level of "endogenous" oxidative stress and to cope with increased free radicals from external sources.

The soxRS regulon mobilizes diverse functions to scavenge free radicals and repair oxidative damage in macromolecules, and other mechanisms that exclude many environmental agents, e.g. nitric oxide, activating expression of heme oxygenase 1 through stabilization of its mRNA.

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Aging: Cells and Metabolism Cellular theory â€Ē Genetics: anti-aging gene â€Ē Cell biochemical metabolism â€Ē Free radicals/antioxidant balance

Aging and Biological SystemsEndocrinology: Insulin-like hormone Immunity : lymphocyte response

Aging and Factors Outside the BodyNutrition-calorie consumptionEnvironment: toxins and detoxification

Page 31: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļŠāļļāļĢïŋ―āļ›āđ‡āļāļĩāļēāļĢāļšāļĢāļĢāļĒāļēāļĒāļŠāļļāļĢïŋ―āļ›āđ‡āļāļĩāļēāļĢāļšāļĢāļĢāļĒāļēāļĒ 1. 1. āļ­āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļˆāļī/āļēāđ€āļ›āđ‡)āļ™āļļāļĄāļēāļāļĩāļ•āļī"āļ­āļŠāļļïŋ―āļ‚āđ‰āļ āļēāļžāđāļĨāļ°āļˆāļī/āļēāđ€āļ›āđ‡)āļ™āļļāļĄāļēāļāļĩāļ•āļī"āļ­āļŠāļļïŋ―āļ‚āđ‰āļ āļēāļžāđāļĨāļ°

āļŠāļĩïŋ―āļ§āļ•āļīāļŠāļĩïŋ―āļ§āļ•āļī2 .2 . āļ­āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļ›āđ‡āļĢāļĄāļēāļ“āļĄāļēāļāļĩāđ€āļāļĩāļ™āļļāļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļ›āđ‡āļĢāļĄāļēāļ“āļĄāļēāļāļĩāđ€āļāļĩāļ™āļļāđ„āļ›āđ‡ āļ—/āļēāđƒāļŦāļąïŋ―āđ€āļāļĩāļ”āđ„āļ›āđ‡ āļ—/āļēāđƒāļŦāļąïŋ―āđ€āļāļĩāļ”āļāļĩāļēāļĢāļ—/āļēāļĨāļēāļĒāļŠāļĩïŋ―āļ§ āļāļĩāļēāļĢāļ—/āļēāļĨāļēāļĒāļŠāļĩïŋ―āļ§ āđ‚āļĄāđ€āļĨāļāļĩïŋ―āļĨ āđ‚āļĄāđ€āļĨāļāļĩïŋ―āļĨ ((āđ‚āļ›āđ‡āļĢāļ•āļīïŋ―āļ™āļļ āđ„āļ‚āđ‰āļĄïŋ―āļ™āļļ āļāļĩāļĢāļ”āļ™āļļāļ§āļ„āļļāļĨïŋ―āļ­āļāļĩāđ‚āļ›āđ‡āļĢāļ•āļīïŋ―āļ™āļļ āđ„āļ‚āđ‰āļĄïŋ―āļ™āļļ āļāļĩāļĢāļ”āļ™āļļāļ§āļ„āļļāļĨïŋ―āļ­āļāļĩ))

3.3. Oxidative stress Oxidative stress āđ€āļāļĩāļ”āļˆāļīāļēāļāļĩāđ€āļāļĩāļ”āļˆāļīāļēāļāļĩāļ­āļ­āļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļ›āđ‡āļĢāļ™āļļïŋ―āļĄïŋ―āļĨāļ­āļŠāļļāļĢāļ°āļĄïŋ―āļ›āđ‡āļĢāļĄāļēāļĄāļēāļāļĩāđ€āļāļĩāļ™āļļāļāļĩāļēāļĢāļ„āļļāļ§āļšāļ„āļļïŋ―āļĄāļ”ïŋ―āļ§āļĒāđāļ­āļ™āļļāļ•āļīāļ­āļ­āļāļĩāļ‹āđāļ”āļ™āļļāļ—ïŋ―āļĄāļēāļĄāļēāļāļĩāđ€āļāļĩāļ™āļļāļāļĩāļēāļĢāļ„āļļāļ§āļšāļ„āļļïŋ―āļĄāļ”ïŋ―āļ§āļĒāđāļ­āļ™āļļāļ•āļīāļ­āļ­āļāļĩāļ‹āđāļ”āļ™āļļāļ—ïŋ―

4. Oxidative stress – cause of several 4. Oxidative stress – cause of several diseasesdiseases

Page 32: GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

āļˆāļīāļšāļāļĩāļēāļĢāļšāļĢāļĢāļĒāļēāļĒāļˆāļīāļšāļāļĩāļēāļĢāļšāļĢāļĢāļĒāļēāļĒ

āļ‚āđ‰āļ­āļšāļ„āļļïŋ―āļ“āļ—ïŋ―*āļ•āļīïŋ―.āļ‡āđƒāļˆāļīāļŸ=āļ‡ āđāļĨāļ°āļ„āļļ/āļēāļ–āļĩāļēāļĄ


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