Oxidative Stress as Marker of Metabolic Disease

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Oxidative Stress as Marker of Metabolic Disease

• D Alberts
• Plavolab
• Development of health products from a natural
  source.

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Balance
Antioxidants
Oxidants
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Oxidative Stress
Antioxidants
Oxidants
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Production of Oxidants

• Reactive Oxygen Species (ROS)
• Produced by the body
• Response to growth factors, cytokines
• Respiration, phagocytosis
• Normal Metabolism

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Antioxidant defenses

• Enzymatic Mechanisms Superoxide Dismutase (SOD),
  Catalase, Glutathione Peroxidase
• Exogenous (Dietary) Antioxidants Ascorbate,
  a-Tocopherol, Carotene, Glutathione, Polyphenols
• Normal Metabolism

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Production of Oxidants Exceed Natural Defenses
Antioxidants
Oxidants
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Sources of Excessive oxidants

• ROS Production Defective Excessive ROS Produced
  - Rheumatoid Arthritis Altered Arachidonic acid
  Metabolism, Inflammatory Bowel Disease, Injury to
  the Central Nervous System, Connective-tissue
  Damage, Inflammation, Diabetes
• Pollution, Toxic gases, Oxygen excess, Radiation
  Tobacco Smoke, excessive exposure to sunlight
• Inactivation Endogenous Antioxidants or Reduced
  Intake of Exogenous Antioxidants Poor nutrition

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DISEASE STATES

• Cancer
• Immune System degeneration
• Neurodegeneration, Stroke
• Aging, Cataract Formation
• Diabetes, Obesity
• Cardiovascular Disease, incl. Hypertension
• Contribute to 33 Deaths
• gt40 Total Medical Expenses

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Carcinogenesis

• Oxidative DNA Modification
• High Levels of oxidative lesions
• Reduced Incidence Populations High Dietary
  Antioxidant Intake

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Immune System degeneration

• Free Radicals, Intracellular, required
  Phagocytosis
• However ! ! !
• Radicals Leach out of White Cells
• Extracellular radicals Attack cell Membranes,
  particularly Destruction of Immune Cells, incl.
  Gene Regulation.
• Reduced Signal Transduction
• ROS cause Abnormal Cell Proliferation

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Neurodegeneration

• Neural Cells Especially Susceptible
• Alzheimers Disease Key Role in Loss of Neurons
  Mitochondrial Abnormalities - ?Energy
• Parkinsons Disease Oxidised Dopamine
  Metabolites Toxic to Nigral Neurons
• Stroke ROS Major Contributor to Damage during
  the Acute Phase.
• Oxidative stress Major Contributor to
  Pathogenesis of Diabetic Nephropathy

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Aging and Cataracts

• Levels of Oxidative Damage Positively Correlated
  with Aging
• Oxidative Mitochondrial Decay Major Contributor
  to Aging
• Cataract formation - Amplification of Aging -
  Oxidation Hallmark Age Related Nuclear
  Cataract Cysteine and Methionine Residues
  Oxidised

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Cardiovascular Disease

• Atherosclerosis Oxidative Damage to Endothelium
  Oxidation of LDL ? Lipid Plaque Accumulation ?
  Atherosclerosis
• Hypertension Excessive O2- uncouples Endothelial
  NO Synthase (eNOS) ? Peroxynitrite Vascular
  Dysfunction
• Endothelial Damage Arteriosclerosis,
  Hypertension, Renal Damage

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Increase Antioxidant Intake
Antioxidants
Oxidants
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Increase Antioxidant Intake

• To Avoid or Minimise these Disease States an
  Increased Antioxidant Intake is Required
• HOWEVER ! ! !

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Too High Antioxidant Intake
Oxidants
Antioxidants
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Too High Antioxidant Intake

• Reactive Species Required for Normal Metabolism
  and Homeostasis
• ROS Required for Phagocytosis
• NOS Required for Endothelial Function Normal
  Blood Pressure

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A Balance Required
Antioxidants
Oxidants
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Oxidative Status Monitoring

• Existing Assays - Specialised Instruments /Staff
• Expensive to Perform
• Not Readily Available to Clinicians and/or
  Patient Population
• Requirement An Easy to Perform, readily
  Available Assay

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Assay under Development

• Instruments Required Standard Clinical
  Chemistry Analyser or Spectrophotometer
• Staff Routine Staff Operating Clinical
  Chemistry Analysers/Spectrophotometers
• Cost of Assay Very Low Cost Kit Form
• Accuracy of Assay Being Compared to
  F2-Isoprostane Assay Regarded as Gold
  Standard - Expensive

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Conclusion

• Clinicians Aware of Oxidative Stress
• Weary to treat with Antioxidants Balance
• Need an Assay to Monitor
• Clinical Laboratories not Able to Offer this
  Service
• An Easy to Perform/Low Cost Assay Under
  Development
• The Assay will lead to an Improved Service by
  Laboratories