GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND THEIR DAMAGING PROPERTIES

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GENERATION OF FREE RADICALS, OXIDATIVE STRESS AND
THEIR DAMAGING PROPERTIES
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E-mail maitrees_at_chiangmai.ac.th
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1. ???????????????????2.
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3. ????????????????????????????????????? 4.
Oxidative stress and health
5. Damaging properties of free radicals
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?????????????? (free radical) ???????????????????
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??????? (unpaired electron) ???????????????
(unstable) ????????? (reactive) ?????????????????
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1. ?????????????quantum mechanics ???????????
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(orbits) ???????????? 2.?????????????????????????
? (sub-orbits) ????????????????? (orbitals) 3.
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1.?????????????????????????? ????????????????????
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down)2.??????????????????????????????????????????
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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 FREE RADiCALS
- Chemical processes or combustion -Consist of a
chain of reactions in two ways 1. based on
products and reactants. 2. based on radicals
(initiating, branching, propagating,
terminating). 
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REACTIVE OXYGEN SPECIES

• ????????????????????????? (O2.-) -
  ??????????????????? (OH.) - ????????????????????
  ? (LOOH.) - ???????????????? (O.) -
  ???????????????????? (H2O2) - ?????????????
  (HClO) - ????????????? (NO)

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Enzymatic or non-enzymatic reactionsFruit
browningBurningsEnginesPhotooxidationRadiation
s OzoneEtc.
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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 REACTION
• The generation of hydroxyl radicals
• O.2 Fe-----gt O2 Fe
• H2O2 Fe--gt OH. OH- Fe
• O.2 H2O2 ---gt O2 OH. OH-

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Generalized Reaction Scheme for Photochemical
Smog Formation
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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
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?????????????????????????????
-??????????????????????????? ( DNA)
-???????????? (mitochondria) -????? (Golgi
apparatus) - ??????? (ribosome) -
???????-??????? (lysosome)
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???????????????? Mitochondria
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Free radicals and excited-state species

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

• Microbiocidal mechanism
• Inflammatory response
• Toxicity of many drugs
• Aging
• Carcinogenesis.
• Certain diseasesocular, neurological,
  psychiatric

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Formation of Free RadicalsRedox reactions
(Reduction-oxidation)
Reactions with exchange of electrons between
reactantsReduction is the gain of electrons R
e- R- Oxidation is the
loss of electronsR- R
e-  Fe2 Fe 3 e- e.g.
electric energy, electrochemical cells,
batteries,
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Peroxidation of Free Radicals

• On Polyunsaturated Lipid (LH)
• L. Lipid alkyl radical
• LOO. Lipid peroxyl radical
• LL Polymerized lipids
• OH. LH ---gt H2O L.
• L. O2 ---gt LOO.
• LOO. H2O ---gt LOOH L.
• L. L. ---gt LL

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????????????????????? -Mitochondria
Mitochondria source and target of free radical
species.
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Oxidative damage of LDL molecule
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Gene Damage and Repair in Aging
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(OXIDATIVE DAMAGE AND DISEASES
????????????????????? - ???????????
?????????????? -?????? ?????? ??????? -????? -
UV, X-ray, g -ray - ??????????? (oxidative
stress) - reactive oxygen species
(ROS) --???????????????????? - ??????????-
??????, ?????
?????????????? - ???????? ?????????? -
??????????????????? - ????????? - ??????????????-
????????????? -Alzheimers disease - ?????????? -
?????????? - ??????--
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Aging Balance of Free Radicals and Antioxidants

• Can You Live to Be 120 Years Old?

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Genetic Responses to Free RadicalsHomeostasis
and Gene Control
Gene 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
• Genetics anti-aging gene
• Cell biochemical metabolism
• Free radicals/antioxidant balance

• Aging and Biological Systems
• Endocrinology Insulin-like hormone
• Immunity lymphocyte response

• Aging and Factors Outside the Body
• Nutrition-calorie consumption
• Environment toxins and detoxification

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LONGEVITY YOU ARE WHAT AND HOW YOU EAT
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1. ?????????????????????????????????????

1. ???????????????????????????? ????????????????????
   ??????? (?????? ????? ????????????)

1. Oxidative stress ?????????????????????????????????
   ???????????????????????????

4. Oxidative stress cause of several diseases
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