Antioxidants /certified fixed orthodontic courses by Indian dental academy

Antioxidants
INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com


Table of contents
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Introduction
Definitions
Free radicals
Antioxidants
Chemo prevention

Free radicals in disease pathogenesis
System/Organ
cvs
brain
kidney
liver
lung
skin
eye
blood
multi-organ diseases

Disease process
atherosclerosis
alzeheimers
renal graft rejection
cirrhosis
oxidant pollutants
solarionizing radiation
catarcts
fanconi’s anaemia
nutritional deficiences

Definitions
• Oxidant-electron acceptor in an oxidationreaction.
• Oxidation-a chemical reaction in which
electrons from one reactant are transferred to
the other reactant.
• Oxidative stress-a pathological change seen
in a living organism in response to excessive
levels of cytotoxic oxidants & free radicals in
the environment.

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Free radicals-unpaired electrons ,highly reactive & unstable enters into reaction
with inorganic/organic chemicals-PROTEINS,LIPIDS,CHO,particularly molecules
in membranes & nucleic acids.


ROS reaction with bio-molecules
• DNA- attack nucleotide base/deoxyribose chain results in
strand breaks,cell killing & neoplastic transformation
of cells(Cheeseman &Slater,93)
• PROTEIN- promotes cross-linking of amino acids results
in fragmentation of peptide chain (Chevion &
Stadman,91)
• LIPID Cell membranes are attacked by oxidising agentslipid peroxidation(Cheeseman,93).
• Malondialdehyde(MDA)-formed by peroxidation of
unsaturated fatty acid, mda reacts with thiobarbituric
acid---TB REACTIVE SUBSTANCES ASSAY(TBRSA)

ANTIOXIDANT SYSTEMS:
• Substance which
prevents damage
caused by oxidation.


MODE OF ACTION
• Chain breaking reactions.eg.alpho tocopherol,acts in
lipid phase to trap”ROD” radical.
• Reducing the conctn of ROS.eg.glutathione
• Scavenging initiating radicals.eg.superoxide
dismutase,acts in aqueous phase to trap superoxide
free radicals.
• Chelating the transition metal catalysts.
Eg: Transferrin,to check iron induced stress


CLASSIFICATION-Modified by Fischer,1988

• Enzymes Antioxidant
• Superoxide dismutase (SOD)
MitochondrialCytoplasmic Extracellular
• Role :Dismutates O2·⁻ to H2O2 .
• Remarks :Contains Manganese (Mn.SOD) , Copper &
Zinc (CuZnSOD),Copper (CuSOD)
• Catalase :Dismutates H2O2 to H2O .Tetrameric
hemoprotein present in peroxisomes.
• Glutathione peroxidase (GSH.Px) ..Removes H2O2
and lipid peroxides .
• Selenoproteins (contains Se2+) Primarily in the cytosol
also mitochondria .Uses GSH

NON ENZAMATIC ANTIOXIDANTS
• Vitamins
• Alpha tocopherol :Breaks lipid peroxidation Lipid
peroxide and O2·⁻ and ·OH scavenger .Fat soluble vitamin.
• Beta carotene: Scavenges ·OH, O2·⁻ and peroxy radicals
Prevents oxidation of vitamin A Binds to transition
metals.
• Ascorbic acid :Directly scavenges O2·⁻, ·OH, and H2O2,
Neutralizes oxidants from stimulated neutrophils
.Contributes to regeneration of vitamin E Water soluble
vitamin

Other Antioxidants
• Retinoids- have antioxidant properties(Prasad,89)but
main function as antiproliferatives.
• CoQ10-Ubiquinone,found in all living cells.Has
antioxidant and enhances immune defenses.
• Albumin-scavenges free radcals(Halliwlel,94)
• Drugs-antioxidant effects(Reilly et al,91)xanthine
oxidase inhibitors,eg allopurinol,folic acid,
• NADPH inhibitors.eg.adenosine,calcium channel
blocker


Antioxidants and trace elements
• Selenium - protective role against cancer (Schwartz
and Foltz,1957)
• Nutrition role of selenium - essential component of
enzyme glutathione peroxidase- participate in AO
protection of cells(Rotruck et- al , 1973)
• Anticarcinogenic effect of SE- se supplements
-reduce cancer risk, acts as modifier of cancer risk.


Where do you find Antioxidants
*Beta Carotene: in foods that are orange in color
such as sweet potatoes, carrots, cantaloupe,
squash, pumpkin and mangos as well as in
some green leafy vegetables
*Lutein: in green leafy vegetables such as collard
greens, spinach, and kale
*Lycopene: in tomatoes, watermelon, papaya,
apricots, and pink grapefruit
*Selenium: in rice, wheat and brazil nuts
*Vitamin A: in liver, sweet potatoes, carrots,
milk, egg yolks and mozzarella cheese
*Vitamin E: in almonds, wheat germ, safflower,
corn, and soybean oils, mangos, nuts, and
broccoli


Sources of Antioxidants
*Vitamin C: in fruits and vegetables, cereals, beef, poultry and fish


Antioxidants and Cancer
-Tumor initiation involves the exposure of normal cells to chemical
or physical carcinogens that alter the DNA of thecells
-The altered genotype of the cell is considered irreversible, but the
initiated phenotype is not fully expressed except in the
presence of a promotor -Promotors cause the clonal expansion of
initiated cells-Tumor initiation and promotion together usually only
produce benign growths-The third stage,malignant conversion is
uncontrolled cellular growth which is only treatedby outside
intervention

-Several studies show that antioxidants may slow or possibly
prevent the development of cancer, however in recent years
clinical trials reached inconsistent conclusions
*Five large scale clinical trials in the 1990s reached differing
conclusions about the effects of antioxidants on cancer

Clinical Trial
1: Chinese Cancer Prevention Study (1993)
-The results showed that a combination of beta-carotene, vitamin
E, and selenium significantly reduced incidence of both gastric
cancer and cancer overall
2: Alpha-Tocopherol/Beta-Carotene Cancer Prevention Study (1994)
-Lung cancer rates of Finnish male smokers increased
significantly with beta-carotene intake and were not affected by
vitamin E
3: Beta-Carotene and Retinol Efficacy Trial (1994)
-Also demonstrated a possible increase in lung cancer associated
with antioxidants
4: 1996 Physician’s Health Study I
-No change in cancer rates associated with beta-carotene taken by
U.S. male physicians
5: 1999 Women’s Health Study
-No benefit or harm from beta-carotene supplementation, vitamin
E research is ongoing

ANTIOXIDANTS AND CARDIOVASCULAR DISEASE

There is a wide range of cardiovascular
diseases:
Coronary Artery Disease (CAD)
Myocardial Infarction (MI) – heart attack
Cardiac Ischemia – insufficient blood and oxygen
supply to a portion of the heart muscle, most
commonly caused by CAD
Atherosclerosis – development of fatty buildups in the
arteries


TREATMENT & PREVENTION OF CVS
• Ecological and epidemiological evidence suggests
that high consumption of fruits and vegetables is
associated with a decreased risk for CD
• Fruits and vegetables, along with teas and red
wines are rich in antioxidants
• Therefore, researchers logically assumed that
antioxidants played a role in this protective
cardiovascular effect


OXIDATIVE DAMAGE & CVS
• There is ample evidence that oxidative damage is
involved in the pathology of atherosclerosis
• LDL oxidation leads to uptake by macrophages
and formation of the foam cell and creates
oxidized lipids that have a pro-inflammatory
response
• Researchers began to investigate the effects of
antioxidants to reverse the effects of ROS and
oxidative

ANTIOXIDANTS & DICHOTOMY
• Epidemiological evidence shows that
antioxidants have a protective or therapeutic
effect on CD
• Clinical trials support antioxidants as
beneficial, neutral, and, in some cases, harmful
• The controversy between research shows that
antioxidant mechanisms in response to
oxidative damage are not completely
understood

CASE STUDIES:ANTIOXIDANTS ARE BENEFICIAL
• Health Professionals’ Follow-up study:
– >39,000 males, 4 year follow-up
– Β-carotene intake is associated with reduced risk of coronary
events; inverse relationship between duration of vitamin E
supplement use and risk in smokers
• Nurses’ Health Study (Stampfer et al):
– >87,000 women, < 8 year follow-up
– Coronary events and vitamin E intake are inversely related,
43% lower in supplement users vs. nonusers; inverse
relationship between risk and duration of supplement use


ANTIOXIDANTS ARE BENEFICIAL
• National Health and Nutrition Examination Survey
(Enstrom et al)
– Inverse relationship between vitamin C intake and
coronary risk; decreased death from coronary heart
disease over 10 year follow-up
• Cambridge Heart AntiOxidant Study (CHAOS)
– ~9,500 subjects age 55 and over with both
symptomatic and asymptomatic CD, secondary
prevention trial, lasted 17 months
– Coronary disease patients benefited from naturally
occurring vitamin E at 2 dose levels – this leads
researchers to believe there is a difference between
natural and supplemental antioxidants


ANTIOXIDANTS -NO BENEFIT/HARM
Physicians’ Health Study
>29,000 male physicians in the US were
randomized to â-carotene, aspirin, both, or
neither for 12 years
No significant benefit or harm of â-carotene on
cardiovascular disease

Women’s Health Study
>40,000 women 45 and older, primary prevention
study on the effects of â-carotene, vitamin E and
low-dose aspirin on major cardiovascular
endpoints
2-year analysis showed no effect from âcarotene supplements

ANTIOXIDANTS ARE HARMFUL
 α-tocopherol β-carotene Study (ATBC)
Tested α-tocopherol, β-carotene, both or neither
for 5-8 years in >29,000 male smokers
No reduction in cardiovascular events in any
treatment; increase in risk of death from
hemorrhagic stroke from vitamin E, increase in
mortality from ischemic heart disease
 β-carotene and Retinol Efficacy Trial (CARET)
Studied the effects of combination of β-carotene
and a form of retinol
Increased risk of cardiovascular disease
mortality


PROPOSALS & RECOMMENDATIONS
• AHA does not recommend antioxidant supplements,
instead following the Food Guide Pyramid is
recommended
• Many researchers have criticized the study designs of all
studies: subjects chosen (at risk vs. not at risk for CVD),
study length, dosage, etc.
• Distribution of other nutrients in foods is similar to that of
antioxidants, thus the trend that fruits and vegetables
reduce cardiovascular disease could be caused by
mechanisms other than their antioxidant vitamin content,
for example: lowering of blood pressure and dietary
factors such as trace elements found to act as antioxidants
in the diet


ANTIOXIDANTS & EXERCISE
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ENDURANCE EXERCISE(ultra distance
race,high altitude training)-free radicalsdamaging to muscles & tissues
Regular exercise-enhances-antioxidants
system-protects body.
EXPERIMENTAL STUDIES-conflicting
Most DATA-VIT-E-protective
RECOMMENDATION-Balanced program
with reglr exercise & 5 serving of
fruit/veg/day
Demanding race/hg altitude training-VIT-E
supplmts,
100-200IU,appxmtly 10 times the RDA/DAY


ANTIOXIDANTS & AGING
• EXCESS FREE RADICALS-cellular damage b,coz
fatty acids,protein are lost in cell membraneUNSTABLE-imbalance b/w flow of nutrient in & out of
cells.
• CEL MEMBRANE-OXIDISED-HARDENS-nutrients
cannot go into cell.
• PUNCTURES-cell collapses-cell fluids drains outAGING-WRINKLES-SAGGY & LEATHERY


ANTIOXIDANTS IN CHEMOPREVENTION
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CHEMOPREVENTIONpharmocological intervention
with specific nutrient or other
chemicals to suppress or
prevent the development of
disease.
CLASSIFIED -BLOCKING
AGENTS-inhibit tumor
initiation
SUPPRESSING AGENTSinhibit tumor
promotion/progression

ANTIOXIDANTS IN ORAL MEDICINE
• USES IN ORAL LESIONS
• LEUKOPLAKIA-SILVERMAN(1960)evaluated vit A(13cRA)topical application,lesions relapsed,as soon treatment was
discontinued.
• Side effects-dry skin,xerostomia,hyper triglyceridemia,chelitis
• STICH ET AL(1991)administrated vit A(60mg/wk)fr 6mocomplete remission of OLK in 57%,reduction of micro-nuclei
cells in 96% of tobacco chewers.
• Beta-Carotene (2.2mmol/wk)-remission 14.8%& reduction of
micronuclei cells in 98%. Vit A (COMPLETELY) & BETA
CAROTENE(50%) suppressed formation of OLK within 6 mo
trial period.But relapsed once treatment was dis continued of
drug.

• SINGH et al(2003)administered lycopene in treatment of
.
OLK,in 3 gp(gpA,gpB,gpC)were given
8mg/day,4mg/day,0(placebo),mean response was
80%,66.25%,12.5% resptly,patients recovrd in gp A,gp
B.This study confirmed lycopene was 3 fold more
effective than beta carotene in preventing cell death by
quenching NOO- radicals,it also protects DNA damage
induced by H2O2.

• LICHEN PLANUS -Treated with ETRETINATE,which
is synthetic retinol,but clinical success
inconsistent,relapse rate was more than 50%within 3
mo.

• ORAL SUBMUCOUS FIBOSIS
• ROLE OF OXIDATIVE STRESS AND ANTIOXIDANTS IN
AETIOPATHOGENESIS ANDMANAGEMENT OF ORAL
SUBMUCOUS FIBROSIS (GUPTA et al,2004).Lipid peroxidation
product, malonaldehyde (MDA) and antioxidants were estimated in
plasma and erythrocytes of 34 cases of oral submucous fibrosis
(OSMF) of different grades with equal numberof healthy controls to
evaluate the association of reactive oxygen species (ROS) and OSMF.
plasma MDA was found to be significantly higher in patients ,as
compared to controls ,plasma beta carotene and vitamin E levels
were found to be decreased significantly in patients, with respect to
healthy controls. After 6 weeks of oral administration of beta-carotene
and vitamin E, patients showed increase in plasma level of these two
antioxidants along with decrease in MDA level associatedwith
clinical improvement.

ANTIOXIDANTS IN PREVENTION OF
SECOND PRIMARY TUMORS

• Patients with SCC of H&N CANCER,
• Hong et al (1990)administered 50-100mg of
13cRA/d given to pts with treated SCC of
oral cavity,pharynx resulted in fewer
second primary cancer.


SUPPLEMENTS AVAILABLE
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Indications-metabolic
disease,CBV,CVS,neurological
diseases,degenerative disease of eye,oral
lesions
Special precaution-high doses of beta
carotene-yellowish of skin(carotenimia)
side effects-diarhoea,yellowing of
palms,etc.
Brands available are
ADENT(spirulina) tab-500mg
ALA-100(alpha-lipoic acid)-cap15mg
ANTOXID-1 TAB -3 times/d-1st 2
months,folwd by 1cap d
BETA SCLERBION
BIO-E
OXYACE

COMMON WAY TO PREVENT DISEASES
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Take Daily
supplements of
antioxidants
Stop Smoking
Diet rich in
fruits and
vegetables (i.e.
green leafy
veggiescollards, kale,
spinach, and
broccoli


REFERENCES
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MEDICAL ONCOLOGY-DEVITA
NUTRITIONAL ONCOLOGY-DADID HABER
NUTRITIONAL HEALING-DENISE MORTIMORE
MEDICAL NUTRITION& DISEASE-GAIL MORRISON
AMERICAN JOURNAL OF CLINICAL
NUTRITION,1991
TRIPLE O ,2003,
NEJM,1990,
INDIAN JOURNAL OF CLINICAL
BIOCHEMISTRY,2004
IMAGES-E NET www.indiandentalacademy.com

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