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Free Radicals, Oxidative Stress and Natural
Antioxidants
by
Maliha Rashid
M.Phil BIOT
PMAS Arid Agriculture University Rawalpindi, Pakistan
1
Table of Contents
1. Free Radicals
2. Types of free radicals
3. Sources of free radicals
4. Reactive Oxygen Species (ROS)
5. Reactions by which Free Radicals are
produced
6. Role of Free Radicals in biological
systems
7. Oxidative Stress
8. Molecular Effect of Oxidative Stress
9. Measurement of Oxidative Stress
10. Protection against ROS Damage
11. Diseases caused by Free Radicals
2
Free Radicals
• molecules having unpaired electrons
• Reactive as they have the tendency to complete their octet
• Unstable –try to become stable by accepting or donating electrons
• Very reactive- very harmful (can damage the surrounding cells) causes
cell injury
• Short life span
3
Types of Free Radicals
1. Superoxide anion (O2
.−)
2. Hydroxyl Peroxyl radical (HOO-)
3. Hydroxyl Radical (OH.)
4. Nitric Oxide (NO.)
5. Peroxynitrite (ONOO.)
4
5
Sources of Free Radicals
Endogenous Sources
Environmental
Sources
6
Endogenous Sources
• Electron Transport Chain
• Nitrite Oxide Synthase
• NADPH Oxidase Reaction/Respiratory Burst
• Xanthine Oxidase Reaction
• Lipoxygenase Pathway (Conversion of arachadonic acid via the lipoxygenase pathway is
associated with an increase of ROS)
• Lipid Peroxidation
7
Respiratory Burst
• Respiratory burst(also called oxidative burst) is the rapid release of reactive
oxygen species ( superoxide anion and hydrogen peroxide) from different types of
cells.
• Usually it denotes the release of these chemicals from immune cells, such as
neutrophils and macrophages because they are infected by different bacteria or
fungi.
8
9
Xanthine Oxidase Reaction
• Xanthine oxidase is the enzyme required to produce uric acid by the
breakdown of purine nucleotides.
• The uric acid itself, as well as the reactive oxygen species released
during the enzymatic reaction, can have detrimental effects on the
body.
• Gout is a common condition that occurs due to elevated uric acid
production via this mechanism.
10
11
Lipid Peroxidation
• Lipid peroxidation is an oxidative chain reaction in which one lipid
molecule after another becomes oxidized to the maximum possible
extent or so as to form a lipid peroxide (i.e., a lipid molecule
containing one or more O–O bonds)
12
13
Environmental Sources
• Alcohol
• Smoking
• Ionizing Radiations
• Drugs
14
Reactive Oxygen Species
• Most important free radicals in the body
• Derived from Oxygen
Examples
1. Superoxide anion (O2
.−)
2. Hydrogen Peroxide (H2O2)
3. Hydroxyl Peroxyl radical (HOO-)
4. Hydroxyl Radical (OH.)
5. Singlet Oxygen (O2)
15
16
Physiological Activities of Free Radicals
• When maintained at low or moderate concentrations, free radicals play several
beneficial roles for the organism.
1. synthesize some cellular structures
2. cellular signaling pathway
3. induction of a mitogenic response
17
Oxidative Stress
• A disturbance in the balance between reactive species/free radicals and
antioxidants
• Under normal conditions, cells are able to balance the production of
oxidants and antioxidants
• Oxidative stress occurs when there is imbalance in the cells due to an
increase in the production of free radicals or a decrease in
antioxidants.
18
19
Effects of Oxidative Stress
• Lipid Peroxidation
• DNA Damage
• Protein Oxidation
• Inactivation of Enzymes
• Cytoskeletal Damage
20
Free Radical Detection
• Single Photon Counting
• Chemiluminscence
• Fluorescent Probes
• Electron Paramagnetic Resonance Spectroscopy
21
Diseases caused by Oxidative Stress
 Cancer mostly due to lipid peroxidation
 Cardiovascular Diseases
 Neurological Diseases such as Parkinson's disease, Alzheimer's disease (AD)
 Respiratory Diseases
 Rheumatoid Arthritis
 Delayed sexual maturation and puberty onset
 Kidney Diseases
22
Natural Antioxidants
23
Table of Contents
1. Antioxidants
2. Natural Antioxidants
3. Mechanism of Action
4. Classification of natural antioxidants
5. Biological Activities of natural antioxidants
24
Antioxidants
• Substances that inhibit or delay oxidation
• Counteract the deterioration of stored food products
• Free radical scavengers
25
Types
Synthetic antioxidants Natural Antioxidants
26
Natural Antioxidants
• Primarily extracts of herbs and plant materials
• Has electron donating and chain breaking properties
• have potential to balance the irregulated oxidative stress
• Protect body against diseases
27
Mechanism of Action
• Inhibit oxidative stress by neutralizing free radicals
• Donate electron to the free radical
• Terminates chain reaction
28
Classification of Natural Antioxidants
1. Vitamins
2. carotenoids
3. polyphenols
4. small antioxidant molecules
5. enzymes
6. trace elements
29
Sources of Natural Antioxidants Explanation
Vitamins Vitamin A, C,E
Carotenoids B-carotene
Polyphenols phenolic acids, coumarins, flavonoids, stilbenes and
lignans
Small antioxidant molecules Enzymes, Ubiquinone, sulfur containing compounds
Trace Elements Selenium
30
Biological Activities
• Anti-inflammatory
• Antiaging
• Anticancer
• Antimicrobial
31
Role in various diseases
Natural Antioxidants Role in diseases
Vitamin E protects against cataracts and restore multidrug
resistance in tumour cells
Polyphenols vasorelaxant and antihypertensive properties
32
References
1. Butnariu and Samfira, J Bioequiv Availab (2012)
2. Pickrell AM, Fukui H, Moraes CT (2009) The role of cytochrome c oxidase deficiency in ROS
and amyloid plaque formation. J Bioenerg Biomembr 41: 453-456.
3. Rizzo AM, Berselli P, Zava S, Montorfano G, Negroni M, et al. (2010) Endogenous antioxidants
and radical scavengers. Adv Exp Med Biol 698: 52- 67.
4. Gustafsson AB, Gottlieb RA (2008) Heart mitochondria: gates of life and death. Cardiovasc Res
77: 334-343.
5. Akinci M, Kosova F, Cetin B, Sepici A, Altan N, et al. (2008) Oxidant/antioxidant balance in
patients with thyroid cancer. Acta Cir Bras 23: 551-554..doi.org/10.4172/jbb.10000e13
33

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Free Radicals, Oxidative Stress and Natural Antioxidants by Maliha Rashid.pptx

  • 1. Free Radicals, Oxidative Stress and Natural Antioxidants by Maliha Rashid M.Phil BIOT PMAS Arid Agriculture University Rawalpindi, Pakistan 1
  • 2. Table of Contents 1. Free Radicals 2. Types of free radicals 3. Sources of free radicals 4. Reactive Oxygen Species (ROS) 5. Reactions by which Free Radicals are produced 6. Role of Free Radicals in biological systems 7. Oxidative Stress 8. Molecular Effect of Oxidative Stress 9. Measurement of Oxidative Stress 10. Protection against ROS Damage 11. Diseases caused by Free Radicals 2
  • 3. Free Radicals • molecules having unpaired electrons • Reactive as they have the tendency to complete their octet • Unstable –try to become stable by accepting or donating electrons • Very reactive- very harmful (can damage the surrounding cells) causes cell injury • Short life span 3
  • 4. Types of Free Radicals 1. Superoxide anion (O2 .−) 2. Hydroxyl Peroxyl radical (HOO-) 3. Hydroxyl Radical (OH.) 4. Nitric Oxide (NO.) 5. Peroxynitrite (ONOO.) 4
  • 5. 5
  • 6. Sources of Free Radicals Endogenous Sources Environmental Sources 6
  • 7. Endogenous Sources • Electron Transport Chain • Nitrite Oxide Synthase • NADPH Oxidase Reaction/Respiratory Burst • Xanthine Oxidase Reaction • Lipoxygenase Pathway (Conversion of arachadonic acid via the lipoxygenase pathway is associated with an increase of ROS) • Lipid Peroxidation 7
  • 8. Respiratory Burst • Respiratory burst(also called oxidative burst) is the rapid release of reactive oxygen species ( superoxide anion and hydrogen peroxide) from different types of cells. • Usually it denotes the release of these chemicals from immune cells, such as neutrophils and macrophages because they are infected by different bacteria or fungi. 8
  • 9. 9
  • 10. Xanthine Oxidase Reaction • Xanthine oxidase is the enzyme required to produce uric acid by the breakdown of purine nucleotides. • The uric acid itself, as well as the reactive oxygen species released during the enzymatic reaction, can have detrimental effects on the body. • Gout is a common condition that occurs due to elevated uric acid production via this mechanism. 10
  • 11. 11
  • 12. Lipid Peroxidation • Lipid peroxidation is an oxidative chain reaction in which one lipid molecule after another becomes oxidized to the maximum possible extent or so as to form a lipid peroxide (i.e., a lipid molecule containing one or more O–O bonds) 12
  • 13. 13
  • 14. Environmental Sources • Alcohol • Smoking • Ionizing Radiations • Drugs 14
  • 15. Reactive Oxygen Species • Most important free radicals in the body • Derived from Oxygen Examples 1. Superoxide anion (O2 .−) 2. Hydrogen Peroxide (H2O2) 3. Hydroxyl Peroxyl radical (HOO-) 4. Hydroxyl Radical (OH.) 5. Singlet Oxygen (O2) 15
  • 16. 16
  • 17. Physiological Activities of Free Radicals • When maintained at low or moderate concentrations, free radicals play several beneficial roles for the organism. 1. synthesize some cellular structures 2. cellular signaling pathway 3. induction of a mitogenic response 17
  • 18. Oxidative Stress • A disturbance in the balance between reactive species/free radicals and antioxidants • Under normal conditions, cells are able to balance the production of oxidants and antioxidants • Oxidative stress occurs when there is imbalance in the cells due to an increase in the production of free radicals or a decrease in antioxidants. 18
  • 19. 19
  • 20. Effects of Oxidative Stress • Lipid Peroxidation • DNA Damage • Protein Oxidation • Inactivation of Enzymes • Cytoskeletal Damage 20
  • 21. Free Radical Detection • Single Photon Counting • Chemiluminscence • Fluorescent Probes • Electron Paramagnetic Resonance Spectroscopy 21
  • 22. Diseases caused by Oxidative Stress  Cancer mostly due to lipid peroxidation  Cardiovascular Diseases  Neurological Diseases such as Parkinson's disease, Alzheimer's disease (AD)  Respiratory Diseases  Rheumatoid Arthritis  Delayed sexual maturation and puberty onset  Kidney Diseases 22
  • 24. Table of Contents 1. Antioxidants 2. Natural Antioxidants 3. Mechanism of Action 4. Classification of natural antioxidants 5. Biological Activities of natural antioxidants 24
  • 25. Antioxidants • Substances that inhibit or delay oxidation • Counteract the deterioration of stored food products • Free radical scavengers 25
  • 27. Natural Antioxidants • Primarily extracts of herbs and plant materials • Has electron donating and chain breaking properties • have potential to balance the irregulated oxidative stress • Protect body against diseases 27
  • 28. Mechanism of Action • Inhibit oxidative stress by neutralizing free radicals • Donate electron to the free radical • Terminates chain reaction 28
  • 29. Classification of Natural Antioxidants 1. Vitamins 2. carotenoids 3. polyphenols 4. small antioxidant molecules 5. enzymes 6. trace elements 29
  • 30. Sources of Natural Antioxidants Explanation Vitamins Vitamin A, C,E Carotenoids B-carotene Polyphenols phenolic acids, coumarins, flavonoids, stilbenes and lignans Small antioxidant molecules Enzymes, Ubiquinone, sulfur containing compounds Trace Elements Selenium 30
  • 31. Biological Activities • Anti-inflammatory • Antiaging • Anticancer • Antimicrobial 31
  • 32. Role in various diseases Natural Antioxidants Role in diseases Vitamin E protects against cataracts and restore multidrug resistance in tumour cells Polyphenols vasorelaxant and antihypertensive properties 32
  • 33. References 1. Butnariu and Samfira, J Bioequiv Availab (2012) 2. Pickrell AM, Fukui H, Moraes CT (2009) The role of cytochrome c oxidase deficiency in ROS and amyloid plaque formation. J Bioenerg Biomembr 41: 453-456. 3. Rizzo AM, Berselli P, Zava S, Montorfano G, Negroni M, et al. (2010) Endogenous antioxidants and radical scavengers. Adv Exp Med Biol 698: 52- 67. 4. Gustafsson AB, Gottlieb RA (2008) Heart mitochondria: gates of life and death. Cardiovasc Res 77: 334-343. 5. Akinci M, Kosova F, Cetin B, Sepici A, Altan N, et al. (2008) Oxidant/antioxidant balance in patients with thyroid cancer. Acta Cir Bras 23: 551-554..doi.org/10.4172/jbb.10000e13 33

Editor's Notes

  1. 1. Phagocytes keeps free radicals and release on the entry of pathogens.. Chronic granulomatous disease.. Defective NADPH pathway.due to which the certain types of bacteria cannot be killed in the body …role in fibroblast, endothelial cells, cardiac myocytes’..Nitric oxide is an important free radical in signaling pathway. Cell-to-cell messgenger required for a proper blood flow modulation..
  2. including atherosclerosis, ischemia, hypertension, cardiomyopathy, cardiac hypertrophy, and congestive heart failure
  3. Vitamin E; sunflower seeds, almonds, spinach, broccoli, .. Vitamin A: Fish oil, liver, fats, carrots …. Carotenoids: Pumpkin, Spinach, tomatoes