antioxidants in dentistry

8/13/2019 Antioxidants in Dentistry

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KMCT DENTAL COLLEGE Manassery, Mukkam

ANTIOXIDANTS AND

THEIR ROLE IN O RAL D ISEASES

Presented By:

Niyas Ummer1st Year PG

Department of Oral Medicine and Radiology


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KMCT DENTAL COLLEGEORAL MEDICINE AND RADIOLOGY

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Overview

Introduction

Pathophysiology of Oxidative Damageo Free radicals and Reactive Oxygen Specieso Mechanism of cell injury and Oxidative stress

Anti-oxidantso Mechanism of actiono Anti-oxidant systemso Classification

Common Anti-oxidantso Rationale for Dietary Anti-oxidanto Commonly used agentso Phytochemicals

Anti-oxidants in Oral Lesionso Indicationso Guidelines for prescribingo Management of various oral lesionso Prevention of Oral Cancero Controversial areaso Mixture of anti-oxidantso Commonly available drugs

Conclusion References


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Introduction

Free RadicalsThey are chemical species with a single unpaired electron in an outer orbital.

Being extremely unstable, they readily react with inorganic and organic chemicals.When generated in cells, they avidly attack nucleic acids, proteins and lipids.Molecules that react with free radicals are themselves converted into other types offree radicals, thus propagating the chain of damage.

Reactive Oxygen Species (ROS)They are a type of oxygen derived free radical whose role in cell injury is wellestablished:

Redox reactions during respiration + Phagocytic leukocytes in inflammation = ROS

Reactive oxygen species cause cell injury by three main reactions:i. Lipid peroxidation of membranes

ii. Cross-linking of proteinsiii. DNA damage

Cell InjuryCell injury in many circumstances involves damage by free radicals:

Ischemia-reperfusion, chemical and radiation injury Toxicity from oxygen and other gases Cellular aging Microbial killing by phagocytic cells Tissue injury caused by inflammatory cells


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Generation of Free radicalsThe production of free radicals is increased in:

i. Absorption of radiant energyii. Enzymatic metabolism of exogenous chemicals

iii. Inflammation

Removal of Free RadicalsFree radicals are inherently unstable and decay spontaneously. Cells have many

non-enzymatic and enzymatic systems that contribute to inactivation of free radicals:i. Superoxide dismutases (SODs)

ii. Glutathione (GSH) peroxidasesiii. Catalaseiv. Endogenous or exogenous antioxidants

Oxidative StressA persistent imbalance between the production of highly reactive molecular

species (e.g. reactive oxygen species (ROS), reactive nitrogen species (RNS) andantioxidant defenses.

Damage caused by such free radicals is determined by their rates of production andremoval. The summary of the processes involved in development of this oxidativestress is outlined below:

1. Production of ROS increases

2. Scavenging systems are ineffective3. Excess of free radicals4. Oxidative Stress

Summary


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Anti-Oxidants

The Rise of AntioxidantsAny substance that when present at low concentrations compared to those of anoxidizable substrate, significantly delays or prevents oxidation of that substrate

Action of Antioxidants

Antioxidant Systems

a) Primary Prevents formation of new radical species

E.g. SOD, GPX, Metal binding proteins

b) Secondary Traps free radicals

E.g. Vitamin E & C, Beta carotene, Uric acid

c) Tertiary Repair biomolecules damaged by free radicals

E.g. DNA repair enzyme, Methionine sulfoxide reductase


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Classification

Common Antioxidants

Rationale for Dietary AntioxidantAn inverse relationship between the low dietary and serum levels of

antioxidants and probability of development of cancer at various sites (includinghead and neck). High consumption of antioxidants was associated with decreasedrisk of head & neck squamous cell carcinomas among smokers, drinkers and thosewith both smoking and drinking habits.

Beta carotene

Sources: Dark green, orange or yellow vegetables and fruits (spinach, carrots,orange, squash, papaya, mangoes and cantaloupes)Mechanism: Scavenging effect (traps peroxyl free radicals in tissue at low partialpressure of oxygen)Location: PlasmaClinical Significance: Deficiency can lead to periodontal destruction


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Alpha Tocopherol

Sources: Plant oil, margarine, wheat germ and green, leafy vegetablesMechanism: Scavenging effect (breaks free radical chain reaction)Location: Plasma, saliva, GCFClinical Significance: Prostaglandin inhibitory effect can contribute in reducingperiodontal inflammation

Ascorbic Acid

Sources: Citrus fruits, cruciferous vegetablesMechanism: Scavenging and preventive (binds metal ion) effect. Act by decreasingnitrosation and also effects the activity of leukocytes and macrophagesLocation: Plasma, saliva, GCF, synovial fluidClinical Significance: Gingival bleeding is a common result of ascorbate depletion

Minerals (zinc, copper, manganese, selenium)

Sources: Legumes, nuts, whole grains, green vegetablesMechanism: Enzyme activators and subunits of antioxidant defense mechanismClinical Significance: Cytotoxic in action


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Curcuminoids

Sources: TurmericMechanism: Inhibits the generation of potent free radicals like superoxide andhydroxyl radicalsClinical Significance: Antibacterial, fungicidal, wound healing, cytotoxic

Epigallocatechin-3-gallate

Sources: Green TeaMechanism: Scavenging effectClinical Significance: Reduce the risk of dental caries and plaque formation.Effective in oral leukoplakia

Spirulina fusiforms

Sources: Blue green micro algaeMechanism: Potent quencher of highly reactive singlet oxygenClinical Significance: Effective in buccal squamous cell carcinoma


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Eugenol

Sources: CloveMechanism: Scavenging and Preventive effect. Enzyme activator for antioxidantactionClinical Significance: Effective in toothache

Lycopene

Sources: TomatoesMechanism: Protecting critical cellular biomolecules, including lipids, lipoproteins,proteins, and DNAClinical Significance: Serum and tissue levels inversely associated with the risk oforal premalignant lesions

PhytochemicalsThey are non-nutrient compounds that have biological activity inside the

human body. They provide colors, taste, and aromas to the fruits and vegetables.They can mimic hormones and suppress the development of diseases.E.g. Phenolic compounds such as flavonoids

They are said to have anti-inflammatory, anti-allergenic, anti-viral, anti-aging, and anti-carcinogenic activity, and also exert protection against heart disease.


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Antioxidants in Oral Lesions

Indications1. Prevention of lesions in high-risk individuals with mucosa that clinically

appears normal with no history of either premalignant or malignant lesion2. Treatment of premalignant oral lesions3. To prevent recurrence of the treated initial lesion or to prevent the

development of a second or a separate primary

Guidelines for PrescribingThe following points should be considered strongly by the dental practitioners

before considering antioxidant therapy:

a) Has oxidative damage been implicated in the disease pathophysiology?b) Is the oxidative activity a central pathophysiological feature of the disease?c) Where is the oxidative damage occurring?

Oral Submucous Fibrosis

Study Kerr AR. Efficacy of oral lycopene in the management of oralsubmucous fibrosis Oral Surgery, Oral Medicine, Oral Pathology, OralRadiology, and Endodontology 2007;103(2): 214 !.

Re"#$e% Ly&' e%e 1 $"*d+y 'r+,,y- ' er + 2 $'%t/ er#'dRe u,t M'ut/ ' e%#%" +,ue 'r t/e +t#e%t /' ed +% + er+"e #%&re+ e '

3.4 $$

Study Ku$+r A- +"e +d# A- Ke,u 5+r 6. Efficacy of lycopene in the management of oral submucous fibrosis Oral Surg Oral Med Oral PathOral Radiat Endod 2007;103:207 13.

Re"#$e% Ly&' e%e 1 $"*d+y 'r+,,yRe u,t Su t+%t#+, #%&re+ e #% t/e $'ut/ ' e%#%"

Study S'$+ Gu t+- M.6.R. Reddy +%d . C. 8+r#%+t/. Role of o!i"ati#e stressan" antio!i"ants in aetiopathogenesis an" management of oral

submucous fibrosis Indian Journal of Clinical Biochemistry 2004- 19(1):13 141.

Re"#$e% et+ &+r'te%e !0 $"- 6#t+$#% A +,$#t+te 2!00


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Leukoplakia

Study S#%"/ M- Kr# /+%+ + R- +"e +d# A- Ke,u 5+r 6.Efficacy of orallycopene in the treatmentof oral leu$opla$ia Oral Oncol 2004;40:!91

.Re"#$e% Ly&' e%e 4 $"*d+y 'r+,,y 'r 3 $'%t/Re u,t Re er +, ' dy ,+ t#& &/+%"e

Premalignant Lesions & Conditions

Study K+u"+r - S#, er$+%- L' + . A clinical trial of antio!i"ant supplements inthe treatment of oral leu$opla$ia Oral Surg Oral Med Oral Path 1994;7 :4 2 .

Re"#$e% et+ &+r'te%e 30 $"*d+y 'r+,,yRe u,t Re"re #'% ' t/e ,e #'%

Oral Lichen Planus

Study A"/+ 8' e#%#- >+r=+%e/- et +,. Efficacy of %urslane in the &reatment ofOral Lichen %lanus Phytother. Res. 2010; 24:240 244.

Re"#$e% ?ur ,+%e 23! $" e@tr+&t- '%e #,, er d+y 'r 3 $'%t/Re u,t A #"%# #&+%t de&re+ e #% +#% #%te% #ty #% 6AS &'re . Me+% dur+t#'% '

&'$ ,ete /e+,#%" /' ed #"%# #&+%t d# ere%&e .

Study C/+#%+%# u N- S#, er$+% S Br- Re#%"',d A- ' tr'$ A-M& Cu,,'&/ C- L'=+d+ Nur >- et +,. A ran"omi'e"( placebocontrolle"( "ouble)blin" clinical trial of curcuminoi"s in oral lichen planusPhytomedicine 2007; *+ (7 ):437 4 .

Re"#$e% 0 $" red%# '%e +%d 2000 $" ' &ur&u$#%'#d er d+y (#% t ' d# #dedd' e )- 'r 7 ee5

Re u,t A,,e #+t#'% ' y$ t'$

Study N#t+ C/+#%+%# u- Er#% M+dde%- >r+%%+ L'=+d+ Nur- S', S#, er$+%.

,igh)"ose curcuminoi"s are efficacious in the re"uction in symptomsan" signs of oral lichen planus Journal of the American Academy of

ermatology - M+y 2012; (!):7!2 7 0.Re"#$e% Cur&u$#%'#d +t d' e ' 000 $"*d #% 3 d# #ded d' eRe u,t Redu&t#'% #% &,#%#&+, #"% +%d y$ t'$


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Prevention of CancerAnti-oxidants play a major role in the later stages of cancer development.

DNA damage, one of the important contributors to cancer, is oxidative in nature.Hence, anti-oxidants can cause the regression of premalignant lesions or inhibit their

development into cancer.

Some antioxidants act through mechanisms other than their antioxidantproperties. Carotenoids, for instance, can enhance immune function and increase gap

junctional communication.

In general, high intake of fruits and vegetables are associated with aprotective effect against cancer.

Controversial AreasIn spite of all the obvious advantages, there is a lack of predictability of

antioxidant therapy and it has not been validated by the scientific method. Highdoses of Vitamin A may have embryotoxic and teratogenic effects. Large doses ofascorbic acid may be associated with the inhibition of ovarian steroidogenesis andincreased probability of abortion.

Mixture of AntioxidantsIndividual antioxidants produce varying degrees of tumor regression only at

very high doses, posing a high risk of toxicity. At lower doses, however, they may be

ineffective or even stimulate the growth of cancer cells. Hence, use of singlevitamins in cancer treatment has no biological or clinical merit.

Lower doses of individual vitamins 13-cis-retinoic acid, sodium ascorbate, d-a-tocopheryl succinate, and polar carotenoids without any b-carotene as part of amixture can be used.

Commonly Available DrugsAdults:

ANTOXID (1 cap TID for 1st 2 months, then 1 cap OD) ACTILIFE (1 tab OD)

A TO Z (1 tab OD), SYR OROVIT (1 tab OD), SYR, DPS SEVENSEAS SEACOD (1 cap OD) VITOMIN-Z SYR ZEVIT (1 cap OD)

Children: KIDICARE (5 ml TID) PEDIC DPS (10-15 dps daily, with milk or juice)


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Conclusion

Antioxidants could be beneficial in people with innate or acquired highbaseline levels of reactive oxygen species but can be harmful in people with lower

innate levels. Although there has been promising results overall benefit: risk ratioshould be considered.

Currently few studies are available to extrapolate the therapeutic effects ofantioxidants in dental practice. A substantial gap still exists in our knowledge ofbioavailability, biotransformation and mechanism of action of antioxidants.

Large scale and unbiased studies addressing the safety and standardizationissue of antioxidants in dentistry are required.

References

1. S. Carnelio, S. A. Khan, G. Rodrigues. Definite, probable or dubious:antioxidants trilogy in clinical dentistry. British Dental Journal 2008; 204:29-32.

2. Arvind Shetti, Vaishali Keluskar, Ashish Aggarwal. Antioxidants: Enhancingoral and general health . Journal of Indian Academy of Oral Medicine and

Radiology 2009; 21(1).

3. Birangane RS, Chole DG, K Sathya Prakash Reddy, Shivaji. A Review ofAntioxidants. Journal of Indian Academy of Oral Medicine and Radiology 2011;23(3):S351-353.

antioxidants in dentistry

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