Antioxidants /endodontic courses

INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com

Introduction
Definitions
Free radicals
Antioxidants
Chemo prevention

System/Organ Disease process
cvs atherosclerosis
brain alzeheimers
kidney renal graft rejection
liver cirrhosis
lung oxidant pollutants
skin solarionizing radiation
eye catarcts
blood fanconi’s anaemia
multi-organ diseases nutritional deficiences

Indian Dental academy
• www.indiandentalacademy.com
• Leader continuing dental education
• Offer both online and offline dental
courses

 Oxidant-electron acceptor in an oxidation-
reaction.
 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.

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

 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
agents-lipid peroxidation(Cheeseman,93).
 Malondialdehyde(MDA)-formed by peroxidation
of unsaturated fatty acid, mda reacts with
thiobarbituric acid---TB REACTIVE
SUBSTANCES ASSAY(TBRSA)

 Substance which
prevents damage
caused by oxidation.

 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

 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 GSHwww.indiandentalacademy.com

 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

 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

 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.

*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 C: in fruits and vegetables, cereals, beef, poultry
and fish
*Vitamin E: in almonds, wheat germ, safflower, corn, and
soybean oils, mangos, nuts, and broccoli

-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 possiblySeveral studies show that antioxidants may slow or possibly
prevent the development of cancer, however in recent yearsprevent the development of cancer, however in recent years
clinical trials reached inconsistent conclusionsclinical trials reached inconsistent conclusions
*Five large scale clinical trials in the 1990s reached differing*Five large scale clinical trials in the 1990s reached differingwww.indiandentalacademy.com

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-carotenewww.indiandentalacademy.com

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

 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

 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

 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

 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

 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

Physicians’ Health StudyPhysicians’ Health Study
>29,000 male physicians in the US were randomized to>29,000 male physicians in the US were randomized to
ââ-carotene, aspirin, both, or neither for 12 years-carotene, aspirin, both, or neither for 12 years
No significant benefit or harm ofNo significant benefit or harm of ââ-carotene on-carotene on
cardiovascular diseasecardiovascular disease
Women’s Health StudyWomen’s Health Study
>40,000 women 45 and older, primary prevention study>40,000 women 45 and older, primary prevention study
on the effects ofon the effects of ââ-carotene, vitamin E and low-dose-carotene, vitamin E and low-dose
aspirin on major cardiovascular endpointsaspirin on major cardiovascular endpoints
2-year analysis showed no effect from2-year analysis showed no effect from ââ-carotene-carotene
supplementssupplements

αα-tocopherol-tocopherol ββ-carotene Study (ATBC)-carotene Study (ATBC)
TestedTested αα-tocopherol,-tocopherol, ββ-carotene, both or neither for 5-8-carotene, both or neither for 5-8
years in >29,000 male smokersyears in >29,000 male smokers
No reduction in cardiovascular events in any treatment;No reduction in cardiovascular events in any treatment;
increase in risk of death from hemorrhagic stroke fromincrease in risk of death from hemorrhagic stroke from
vitamin E, increase in mortality from ischemic heartvitamin E, increase in mortality from ischemic heart
diseasedisease
ββ-carotene and Retinol Efficacy Trial (CARET)-carotene and Retinol Efficacy Trial (CARET)
Studied the effects of combination ofStudied the effects of combination of ββ-carotene and a-carotene and a
form of retinolform of retinol
Increased risk of cardiovascular disease mortalityIncreased risk of cardiovascular disease mortality

 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

 ENDURANCE EXERCISE(ultra distance race,high
altitude training)-free radicals-damaging 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

 EXCESS FREE RADICALS-cellular damage
b,coz fatty acids,protein are lost in cell
membrane-UNSTABLE-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
out-AGING-WRINKLES-SAGGY &
LEATHERY

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

 USES IN ORAL LESIONS
 LEUKOPLAKIA-SILVERMAN(1960)evaluated vit A(13-
cRA)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 6mo-
complete 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.www.indiandentalacademy.com

 LICHEN PLANUS -Treated with ETRETINATE,which is
synthetic retinol,but clinical success inconsistent,relapse
rate was more than 50%within 3 mo.
 presentstudy shows possibility of ROS playing a part
inaetiopathogenesis of the disease, OSMF andadministration of
nutrient antioxidants may haveprotecting effect with clinical
improvement

 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 twowww.indiandentalacademy.com

 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.

 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

 Take Daily
supplement
s of
antioxidants
 Stop
Smoking
 Diet rich in
fruits and
vegetables
(i.e. green
leafy
veggies-
collards,
kale,
spinach,
and broccoli

 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

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