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ROS & Health
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Reactive Oxygen Species ROS
ROS are free radical containing molecules
Highly reactive
Generated by smoking, irradiation,inflammation, glycoxidation, AND
Lipid Oxidation
Linked to disease & aging processes
Lee et al 2004. Comp Reviews Food Sci. Safety 3:21-33
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ROS and Health
Oxidative stress increase- caused byantioxidant deficient diets and/or increased
production of ROS
Balance between ROS level and anti-oxidative
capacity shifted
Increased level of ROS results in: DNA and Protein modification
Sets stage for disease & degeneration
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Principle Factors
Superoxide anion (O2
) - from mitochondrial
ET reductions of O2water
Hydroxyl radical (OH) - in the presence of
Cu/FeO2
+ H2O2OH + OH-+O2
Hydrogen peroxide (H2O2) - from SOD
Singlet oxygen (1O2) - from photosensitizer
(chlorophyll, myoglobin, hemoglobin) + O2
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Additional Factors
Peroxyl (ROO) & Alkoxyl (R) radicals - from UVlight, Cu/Fe, O2
Nitric oxide (NO) and dioxide (NO2) radicals -
from R enzymatically, or peroxy radical + NO
Peroxynitrite (OONO-) from NO and superoxide
anion
Lipoxygenase- activated by peroxide oxidation of Fe(+2+3), especially active with free PUFA
(liberated by lipase action)
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Lipid Oxidation & Aging
Cell membranes are primary targets (high inunsaturated lipid)
Products of lipid oxidation reactions
Malonaldehyde Oxidized LDL
Oxidized CholesterolContributes to age-related illness - diabetes,
atherosclerosis, inflammation
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Oxygen Species-Lewis Structures
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Lipid Free Radical
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Protein Oxidation
ROS attack proteins
Hydroxyl Radical
Lipid oxidation products(e.g., aldehydes)
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Nucleic Acid Modification
Modification by OH radical results in
8-Hydroxydeoxyguansine
GA (= a mutation)
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Neutraceuticals
Compounds with biological importanceabove and beyond their nutritional value
Purported benefits Disease prevention
Slowing of aging
Reduction of ROS
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Antioxidant Neutraceuticals
Antioxidative enzymesHydrogen donating neutraceuticals
Metal Chelators
Singlet Oxygen quenchersTocopherols
Ascorbates
CarotenoidsPolyphenols
Lipoic acids
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Antioxidative Enzymes
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AntioxidantE
nzymes
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Tocopherol
Tocopherol activity linked to Reduction of heart disease
Delay of Alzheimers
Prevention of cancer
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Ascorbic acid
Associated with: Prevention of heart disease
Prevention of cancer
Ascorbates are excellent H donors
(terminate free radical reactions)
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Synergistic Action Ascorbate-Tocopherol
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CarotenoidsAssociated with prevention of:
Atherosclerosis
Macular degeneration
Colorectal cancer
Mechanism of action Highly efficient quencher of singlet oxygen
H donation to free radical
Forms without ionone ring more potentantioxidant activity
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Carotenoids
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Flavonoids
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Isoflavonoids
Soybean
Genistein high conc
Glycosides
AglyconesAntiox activity as
H donor
Metal Chelating
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FRS-Resonance Delocalization
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Lipoic Acid
Both forms scavenge ROSRegenerate GSH
Prevent oxidative damage to proteins
H donor
Metal chelator
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3,5,4-trihydroxystilbene (phytoalexin)
Flavonoid polyphenol
Inhibits fungal infection in plants
The French Paradox
Resveratrol
King et al. Comp. Rev. Food Sci. Food Safety. 2006. 5: 65-70.
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Resveratrol Foods
Numerous plants Extracts of eucalyptus, spruceherbal
medicines
Peanuts
Grapes
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Resveratrol Forms
cis
trans
Glycosides (Piceid)
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Wine Fermentation
Resveratrol associated with skins
Trans isoform more abundant than cis
Piceid forms decrease with fermentation
Extraction efficiency increases with
ethanol content
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Resveratrol Antioxidant Activity
Better hydroxy radical scavenger capacity
than vitamin C or E
Delay or inhibit oxidative stress linked to
macular degeneration
Reduces lipid peroxidation, oxidation of
LDL, (conditions linked to atherosclerosis)
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Resveratrol & Cardiovascular Health
Inhibits platelet aggregation (Limits LPS +
thrombin-stimulated platelet adhesion)
Vaso-relaxation results in lower blood
pressure
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Resveratrol Anticancer Activity
Anti-proliferative effects
Inhibits tumor progression in vitro
Induces apoptosis
Piceatannol (commercial analog)
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Anti-inflammatory Effects
Inhibits inflammatory cytokine action
Tumor Necrosis Factor- (TNF-)
Interleukin-1
(IL-1
)COX-2
May be effective in controlling diabetes
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Phytoestrogenic Activity
Resveratrol is structurarly similar to
Diethylstilbestrol (DES)
Estrogenic activity linked tocardio-protective effect
Inhibits AGE product damage
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Signal Transduction Modulator
Resveratolsbeneficial effects may be linked to
its potential to modulate signal transduction
pathways
Mitogen Activated Protein Kinases MAPK
pathway Activation of p53 protein
Suppression NF-B and AP-1 through the
inhibition of signaling cascades.
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Neutraceutical Questions
Efficacy vs side effects Which is best?? Foods, supplements, or pure
form
Effects of processing? Thermal treatment hasnegative affects
Development of Pharma-foods ?
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Resveratrol BioavailabilityIn cell culture:
Good passive absorption Trans piceid absorption rate limiting
Converted to sulfate form in the cells
In vivo Ethanol does not affect absorption
Side effects with high oral dose
Interaction with blood thinners No proof of positive effect in clinical
studies
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