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Antioxidants
Dr. Arun Panwar
21/01/2020
Contents
• Introduction
• Concept of free radicals
• Free radical damage
• Oxidative stress
• Antioxidant protection
• Classification of antioxidants
• Retinoids , Vitamin C, Vitamin E
• Enzymatic antioxidants
• Role of antioxidants in cancer
• Antioxidants in periodontal disease
• Antioxidants in oral lesions
• Antioxidant combinations
• Conclusion
Introduction
Definition:
• Chemical: A substance that opposes oxidation
or inhibits reactions promoted by oxygen or
peroxides.
• Biological: Synthetic or natural substances
that prevent or delay deterioration of a
product or are capable of counteracting the
damaging effects of oxidation in animal
tissues.
Concept of Free Radicals
• Free radicals are chemically active atoms that have a
charge due to an excess or deficient number of
electrons.
• Reactive oxygen species are the most biologically
significant free radicals. Include superoxide and
hydroxyl.
• Free radicals and other ROS are derived either from
normal metabolic processes in the human body or
from exogenous sources.
• They are highly unstable due to presence of one or
more unpaired electrons.
• They scavenge the body to grab or donate electrons,
thereby damaging cells, proteins, and DNA.
Classification of antioxidants
According to mode of action:
1) Scavenging antioxidants
• Vitamin E, C, carotenoids and curcumin
2) Preventive antioxidants
• Transferrin, lactoferrin, cerruloplasmin &
desferrioxamine
3) Enzyme antioxidants
• Superoxide dismutase, glutathione
peroxidase & catalase
According to type
Enzymatic
• Superoxide dismutase, glutathione
peroxidase, catalase
Non-enzymatic
• Nutrient: Alpha tocopherol, β- carotene,
ascorbate , selenium
• Non-nutrient: Uric acid, peptides.
Antioxidant Process
• Antioxidants block the process of oxidation by
neutralizing free radicals.
• In doing so, the antioxidants themselves
become oxidized.
• Because of this, there is a constant need to
replenish our antioxidant resources.
Mechanism of action
• Antioxidants neutralise free radicals by
donating one of their electrons, which ends
the electron stealing reaction.
1. Chain breaking or scavenging, such as Vit. E
Vit. C or Vit. A
2. Preventative antioxidants
• Mainly protein in nature
• Function mainly by sequestering transition
metal ions and preventing Fenton reactions
(e.g., albumin, lactoferrin)
Mechanism Of action
1. Act as hydrogen donors to chelate metal ions
such as iron and copper, by inhibiting the
oxidation of low-density lipoproteins (LDL).
They reduce or inhibit free radicals by transfer
of a hydrogen atom, from its hydroxyl group
with a peroxyl radical (ROO•)
2. Based on the hydrongen atom transfer (HAT)
to peroxyl radicals, the inactivation of singlet
oxygen (SET), and the elimination of molecular
oxygen.
Food sources of antioxidant vitamins
• Vitamin C – citrus fruits
• Vitamin E
• Carotenoids
• α carotene: Yellow-orange vegetables and
fruits, dark green vegetables.
• βcarotene: carrots
• Lycopene: tomato
• Lutein and zeaxanthine: Dark green leafy
vegetables.
Therapeutic Use of Antioxidants for
Oral Lesions
• Prevention of lesions in high-risk individuals
• Treatment of premalignant oral lesions
• In patients with previous history of malignancy to
prevent recurrence.
• Tobacco pouch keratosis
• Oral Leukoplakia
• Oral Lichen Planus
• Oral Submucous Fibrosis
• Oral Cancer
Periodontal Diseases
• Inflammatory disease
• Free radicals and reactive oxygen species
(ROS) are responsible for the inflammatory
response.
• Periodontal pathogens induce ROS
overproduction and thus causing collagen and
periodontal tissue breakdown.
• ROS are scavenged by antioxidants,
minimizing the collagen breakdown.
• Therefore, low levels of antioxidants are a risk
factor for periodontal diseases.
• Free radicals are released as a result of
bacterial clearance and killing.
• Systemic glutathione (GSH) is decreased with
inflammation.
• Periodontal tissue depends on natural
antioxidants to overcome this oxidative stress
and maintain balance.
• When antioxidants are depleted, the ability of
gingival tissue to overcome oxidative stress
and control the bacterial damage gets
compromised.
Dental Caries
• Recently, it has been claimed that the imbalances
in levels of free radicals, ROS and antioxidants in
saliva play an important role in the onset and
development of dental caries.
• Salivary peroxidase is the major constitutes of the
salivary antioxidant system.
• It brings the control on oral bacteria which lead
to dental caries.
• Salivary peroxidase catalyzes the per-oxidation of
thiocyanate ion (SCN-) to generate OSCN (more
stable)
• This inhibits the growth and metabolism of many
micro-organisms, thereby inhibiting caries.
Oral Cancer and Premalignant
• Preventive and therapeutic potential
• Flavinoid antioxidants have ability to
• Cell growth and proliferation of oralcarcinoma
• They protect the lipids and other membrane
molecules against oxidative damage by
intercepting oxidants before they try to destroy
the tisuues.
• Vitamin such as A, Beta carotene, C, E, B12 -
Cancer prevention and control.
• Leukoplakia
• Nitric oxide (NO) radicals in tobacco smoke
and products are carcinogenic and implicated
in pathogenesis of leukoplakia.
• Lycopene has been found to be 3 fold more
effective than beta-carotene in preventing cell
death by quenching of nitric oxide radicals.
Oral lichen planus
• Retinoids are used both topically and
systemically to control OLP because of their
anti keratinizing and immunomodulatory
effects.
Oral submucous fibrosis
• Oral submucous fibrosis is a chronic insidious
and progressive disease involving oral mucosa.
• Studies have shown that the process of
malignant transformation in OSMF by
generation of reactive oxygen species which
act by initiating lipid per-oxidation.
• Non-enzymatic antioxidants like β carotene
and vitamin E have shown to be preventive.
Lycopene
• Lycopene is one of the most potent antioxidants
primarily present in tomatoes.
• Lycopene prevents carcinogenesis by protecting
critical cellular biomolecules, including lipids,
lipoproteins, proteins, and DNA.
• According to various studies, lycopene, when
given in the dosage of 4-8 mg/day orally for 3
months,leads to the reversal of dysplastic
changes in leukoplakia and
• When given in the dosage of 16 mg/day leads to
substantials increase in the mouth opening in oral
submucous fibrosis.
• Recommended the daily intake - 3.7 mg.
Beta Carotene
• Family of antioxidant phytonutrients
• Include b-carotene (carrots), lycopene
(tomatoes), and lutein (spinach).
• Serum beta carotene levels have been found to
decrease in various oral premalignant conditions.
Actions:
• Enhance the immune response.
• Inhibit mutagenesis.
• Antioxidant properties- Free radical trapping,
especially peroxyl and hydroxl.
• Dosage: 30 mg/day
Retinoids
• Retinoids comprise a family of isoprenoid
lipids which include vitamin A (retinol)
Actions:
• Regulates cell proliferation & differentiation &
activation of tumor suppressor genes.
• RETINO-A [cream] (tretinoin)
• BETA-SCLEROBION [cap] (beta carotene 0.5
mg, carotenoids 0.5 mg, selenium, vitamin C
100 mg)
Ascorbic acid
• Vitamin C is required for synthesis of collagen and
neurotransmitters.
• Ascorbate is as an antioxidant.
Mechanism of action
1) It is a water soluble chain breaking antioxidant.
2) It prevents formation of carcinogens from
precursor compounds.
• Antioxidant properties
• Immune related functions
• Daily Requirement: 40 – 60 mg
• VITAMIN C [chewable tablet]
Alpha tocopherol (Vit. E)
• There are 4 tocopherols & tocotretiniol isomers
(α,β,γ,δ).
• α tocopherol has the highest antioxidant activity.
• More of an antioxidant than a vitamin.
Mechanism of action:
• It is a chain breaking antioxidant.
• Inhibits P53tumour suppressor gene
• Inhibits conversion of nitrites to nitrosamines.
• Daily requirement – 25-30 mg
• TOCOFER [soft-gelatin caps] (Vitamin E acetate)
Naturally available antioxidants
Curcumin
• Potent antioxidant found in turmeric.
• Free radical scavenging activity.
• Inhibits lipid per-oxidation.
Spirulina
• Blue green algae with high selenium,
• vitamin A and E content.
The antioxidant enzymes
Catalase
• Located in peroxisomes, which contain enzymes
capable of generating hydrogen peroxide.
• Greatest activity in liver and erythrocytes.
Glutathione peroxidase
• Catalyzes the oxidation of glutathione
• Glutathione peroxidases require selenium at the
active site.
Antioxidant combinations
• Individual antioxidant vitamins produce tumor
regression only at very high doses, which causes
toxicity, especially seen with retinoid derivatives.
• At lower doses, they may be ineffective or stimulate
the growth of cancer cells.
• ANTOXID [caps] – (Beta carotene 10 mg, copper 1 mg,
manganese 2 mg)
• ELDERVIT-ZC [caps] – (Mixed carotene 10.33 mg,
chromium 65 mcg, copper 1 mg)
• LYCOSTAR[soft-gelatin caps] – (lycopene 5000 mcg,
selenium dioxide 75 mcg, vitamin A 2500 IU)
• MMO3 [cap] – (chromium 100 mcg, copper 1 mg,
docosahexaenoic acid 100 mg, eicosapentaenoic acid
150 mg, fat 250 mg, Poly unsaturated fatty acid 250
mg, folic acid 300 mcg)
Limitations
• High doses of vitamin A showed to have embryotoxic
and teratogenic effects.
• Large doses of vitamin C (ascorbic acid) may be
associated with the inhibition of ovarian
steroidogenesis and increased probability of abortion.
• Studies have proved:
• Embrotoxicity of Vit. A after daily dose of 0.10 mg/kg
• Teratogenicity of vitamin A after daily doses 0.13
mg/kg
• Maximum intake has been recommended to 0.05
mg/kg of maternal weight.
Conclusion
• Protection against free radicals can be
enhanced by ample intakes of dietary
antioxidants.
• Efforts should be made to ensure an optimum
intake of foods containing these important
molecules.
"Reach for a carrot before cancer reaches you"
“Let food be your medicine”

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Antioxidants

  • 2. Contents • Introduction • Concept of free radicals • Free radical damage • Oxidative stress • Antioxidant protection • Classification of antioxidants • Retinoids , Vitamin C, Vitamin E • Enzymatic antioxidants • Role of antioxidants in cancer • Antioxidants in periodontal disease • Antioxidants in oral lesions • Antioxidant combinations • Conclusion
  • 3. Introduction Definition: • Chemical: A substance that opposes oxidation or inhibits reactions promoted by oxygen or peroxides. • Biological: Synthetic or natural substances that prevent or delay deterioration of a product or are capable of counteracting the damaging effects of oxidation in animal tissues.
  • 4.
  • 5. Concept of Free Radicals • Free radicals are chemically active atoms that have a charge due to an excess or deficient number of electrons. • Reactive oxygen species are the most biologically significant free radicals. Include superoxide and hydroxyl. • Free radicals and other ROS are derived either from normal metabolic processes in the human body or from exogenous sources. • They are highly unstable due to presence of one or more unpaired electrons. • They scavenge the body to grab or donate electrons, thereby damaging cells, proteins, and DNA.
  • 6.
  • 7.
  • 8.
  • 9. Classification of antioxidants According to mode of action: 1) Scavenging antioxidants • Vitamin E, C, carotenoids and curcumin 2) Preventive antioxidants • Transferrin, lactoferrin, cerruloplasmin & desferrioxamine 3) Enzyme antioxidants • Superoxide dismutase, glutathione peroxidase & catalase
  • 10. According to type Enzymatic • Superoxide dismutase, glutathione peroxidase, catalase Non-enzymatic • Nutrient: Alpha tocopherol, β- carotene, ascorbate , selenium • Non-nutrient: Uric acid, peptides.
  • 11. Antioxidant Process • Antioxidants block the process of oxidation by neutralizing free radicals. • In doing so, the antioxidants themselves become oxidized. • Because of this, there is a constant need to replenish our antioxidant resources.
  • 12. Mechanism of action • Antioxidants neutralise free radicals by donating one of their electrons, which ends the electron stealing reaction. 1. Chain breaking or scavenging, such as Vit. E Vit. C or Vit. A 2. Preventative antioxidants • Mainly protein in nature • Function mainly by sequestering transition metal ions and preventing Fenton reactions (e.g., albumin, lactoferrin)
  • 13. Mechanism Of action 1. Act as hydrogen donors to chelate metal ions such as iron and copper, by inhibiting the oxidation of low-density lipoproteins (LDL). They reduce or inhibit free radicals by transfer of a hydrogen atom, from its hydroxyl group with a peroxyl radical (ROO•) 2. Based on the hydrongen atom transfer (HAT) to peroxyl radicals, the inactivation of singlet oxygen (SET), and the elimination of molecular oxygen.
  • 14.
  • 15. Food sources of antioxidant vitamins • Vitamin C – citrus fruits • Vitamin E • Carotenoids • α carotene: Yellow-orange vegetables and fruits, dark green vegetables. • βcarotene: carrots • Lycopene: tomato • Lutein and zeaxanthine: Dark green leafy vegetables.
  • 16. Therapeutic Use of Antioxidants for Oral Lesions • Prevention of lesions in high-risk individuals • Treatment of premalignant oral lesions • In patients with previous history of malignancy to prevent recurrence. • Tobacco pouch keratosis • Oral Leukoplakia • Oral Lichen Planus • Oral Submucous Fibrosis • Oral Cancer
  • 17. Periodontal Diseases • Inflammatory disease • Free radicals and reactive oxygen species (ROS) are responsible for the inflammatory response. • Periodontal pathogens induce ROS overproduction and thus causing collagen and periodontal tissue breakdown. • ROS are scavenged by antioxidants, minimizing the collagen breakdown. • Therefore, low levels of antioxidants are a risk factor for periodontal diseases.
  • 18. • Free radicals are released as a result of bacterial clearance and killing. • Systemic glutathione (GSH) is decreased with inflammation. • Periodontal tissue depends on natural antioxidants to overcome this oxidative stress and maintain balance. • When antioxidants are depleted, the ability of gingival tissue to overcome oxidative stress and control the bacterial damage gets compromised.
  • 19. Dental Caries • Recently, it has been claimed that the imbalances in levels of free radicals, ROS and antioxidants in saliva play an important role in the onset and development of dental caries. • Salivary peroxidase is the major constitutes of the salivary antioxidant system. • It brings the control on oral bacteria which lead to dental caries. • Salivary peroxidase catalyzes the per-oxidation of thiocyanate ion (SCN-) to generate OSCN (more stable) • This inhibits the growth and metabolism of many micro-organisms, thereby inhibiting caries.
  • 20. Oral Cancer and Premalignant • Preventive and therapeutic potential • Flavinoid antioxidants have ability to • Cell growth and proliferation of oralcarcinoma • They protect the lipids and other membrane molecules against oxidative damage by intercepting oxidants before they try to destroy the tisuues. • Vitamin such as A, Beta carotene, C, E, B12 - Cancer prevention and control.
  • 21. • Leukoplakia • Nitric oxide (NO) radicals in tobacco smoke and products are carcinogenic and implicated in pathogenesis of leukoplakia. • Lycopene has been found to be 3 fold more effective than beta-carotene in preventing cell death by quenching of nitric oxide radicals.
  • 22. Oral lichen planus • Retinoids are used both topically and systemically to control OLP because of their anti keratinizing and immunomodulatory effects.
  • 23. Oral submucous fibrosis • Oral submucous fibrosis is a chronic insidious and progressive disease involving oral mucosa. • Studies have shown that the process of malignant transformation in OSMF by generation of reactive oxygen species which act by initiating lipid per-oxidation. • Non-enzymatic antioxidants like β carotene and vitamin E have shown to be preventive.
  • 24. Lycopene • Lycopene is one of the most potent antioxidants primarily present in tomatoes. • Lycopene prevents carcinogenesis by protecting critical cellular biomolecules, including lipids, lipoproteins, proteins, and DNA. • According to various studies, lycopene, when given in the dosage of 4-8 mg/day orally for 3 months,leads to the reversal of dysplastic changes in leukoplakia and • When given in the dosage of 16 mg/day leads to substantials increase in the mouth opening in oral submucous fibrosis. • Recommended the daily intake - 3.7 mg.
  • 25. Beta Carotene • Family of antioxidant phytonutrients • Include b-carotene (carrots), lycopene (tomatoes), and lutein (spinach). • Serum beta carotene levels have been found to decrease in various oral premalignant conditions. Actions: • Enhance the immune response. • Inhibit mutagenesis. • Antioxidant properties- Free radical trapping, especially peroxyl and hydroxl. • Dosage: 30 mg/day
  • 26. Retinoids • Retinoids comprise a family of isoprenoid lipids which include vitamin A (retinol) Actions: • Regulates cell proliferation & differentiation & activation of tumor suppressor genes. • RETINO-A [cream] (tretinoin) • BETA-SCLEROBION [cap] (beta carotene 0.5 mg, carotenoids 0.5 mg, selenium, vitamin C 100 mg)
  • 27. Ascorbic acid • Vitamin C is required for synthesis of collagen and neurotransmitters. • Ascorbate is as an antioxidant. Mechanism of action 1) It is a water soluble chain breaking antioxidant. 2) It prevents formation of carcinogens from precursor compounds. • Antioxidant properties • Immune related functions • Daily Requirement: 40 – 60 mg • VITAMIN C [chewable tablet]
  • 28. Alpha tocopherol (Vit. E) • There are 4 tocopherols & tocotretiniol isomers (α,β,γ,δ). • α tocopherol has the highest antioxidant activity. • More of an antioxidant than a vitamin. Mechanism of action: • It is a chain breaking antioxidant. • Inhibits P53tumour suppressor gene • Inhibits conversion of nitrites to nitrosamines. • Daily requirement – 25-30 mg • TOCOFER [soft-gelatin caps] (Vitamin E acetate)
  • 29. Naturally available antioxidants Curcumin • Potent antioxidant found in turmeric. • Free radical scavenging activity. • Inhibits lipid per-oxidation. Spirulina • Blue green algae with high selenium, • vitamin A and E content.
  • 30. The antioxidant enzymes Catalase • Located in peroxisomes, which contain enzymes capable of generating hydrogen peroxide. • Greatest activity in liver and erythrocytes. Glutathione peroxidase • Catalyzes the oxidation of glutathione • Glutathione peroxidases require selenium at the active site.
  • 31. Antioxidant combinations • Individual antioxidant vitamins produce tumor regression only at very high doses, which causes toxicity, especially seen with retinoid derivatives. • At lower doses, they may be ineffective or stimulate the growth of cancer cells. • ANTOXID [caps] – (Beta carotene 10 mg, copper 1 mg, manganese 2 mg) • ELDERVIT-ZC [caps] – (Mixed carotene 10.33 mg, chromium 65 mcg, copper 1 mg) • LYCOSTAR[soft-gelatin caps] – (lycopene 5000 mcg, selenium dioxide 75 mcg, vitamin A 2500 IU) • MMO3 [cap] – (chromium 100 mcg, copper 1 mg, docosahexaenoic acid 100 mg, eicosapentaenoic acid 150 mg, fat 250 mg, Poly unsaturated fatty acid 250 mg, folic acid 300 mcg)
  • 32. Limitations • High doses of vitamin A showed to have embryotoxic and teratogenic effects. • Large doses of vitamin C (ascorbic acid) may be associated with the inhibition of ovarian steroidogenesis and increased probability of abortion. • Studies have proved: • Embrotoxicity of Vit. A after daily dose of 0.10 mg/kg • Teratogenicity of vitamin A after daily doses 0.13 mg/kg • Maximum intake has been recommended to 0.05 mg/kg of maternal weight.
  • 33. Conclusion • Protection against free radicals can be enhanced by ample intakes of dietary antioxidants. • Efforts should be made to ensure an optimum intake of foods containing these important molecules. "Reach for a carrot before cancer reaches you" “Let food be your medicine”