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ISSN 0975-8437

INTERNATIONAL JOURNAL OF DENTAL CLINICS 2011:3(2): 44-47

REVIEW ARTICLE

Reactive Oxygen Species and Antioxidants in Periodontics: A Review


Alok S harma, S wati S harma

Abstract
Various forms of antio xidants have been introduced as an approach to fight dental d iseases and
improve general gingival health. Th is article focuses on the classificat ion of antioxidants and the link
between oxidative stress and periodontal disease.
Key Words: Oxidative Stress;Antioxidants;Periodontitis
Received on: 15/12/2010
Accepted on: 22/12/2010
Periodontitis is a term used to describe
an inflammatory process, initiated by the plaque
biofilm, that leads to loss of periodontal
attachment to the root surface and adjacent
alveolar bone and which ult imately results in
tooth loss.(1) Primary etio logic agents for
gingival and periodontal diseases have been
shown to be predominantly gram negative
anaerobic or facultative anaerobic bacteria
within the sub gingival b iofilm.(2) However the
majority of periodontal tissue destruction is
caused by an exaggerated host response to those
organisms and their products.(3)
The neutrophils play a p ivotal role in
host defense and are the first line of defense
against this infectious periodontal disease. (4)
Neutrophils have several selective mechanis ms
for controlling bacterial invasion, including both
intracellular and extracellular o xidative and
non-oxidat ive killing mechanisms.(4) The
oxidative killing mechanism of neutrophils and
other phagocytes involves the formation of
reactive o xygen species (ROS).(5) Free radicals
are a family of h ighly reactive and divers e
species, capable of extracting electrons and
thereby oxid izing a variety of b io mo lecules
vital to cell and tissue function, which not only
includes oxygen free radicals, but also nitrogen
and chlorine species.(4)
In recent years, the term "reactive
oxygen species" (ROS) has been adopted to
include mo lecules such as hydrogen peroxide
(H2 O2 ), hypochlorous acid (HOCI) and singlet
oxygen (1 O2 ), which though, not radical in
nature, are capable of radical transformat ion in
the extra and intracellular environments.(6)
Whilst most ROS have extremely short
half-lives, they can cause substantial tissue
damage by initiat ing free radical chain reactions.
Therefore the body contains a number of
protective Anti-Oxidant (AO) mechanis ms,
whose specific role is to remove harmful
oxidants (ROS), as soon as they form, or to
repair the damage caused by ROS in viv.(6)

INT ERNA TIONA L JOURNA L OF D ENT AL CL IN ICS

In normal physiology, there is a


dynamic equilibriu m between ROS activity and
antioxidant defense capacity and when that
equilibriu m shifts in favour of ROS, either by
reduction in anti-o xidant defenses or an increase
in ROS p roduction or activity, oxidative stress
results. This imbalance between the ROS-AO
has been implicated as one of the progressive or
pathogenic factors for periodontal disease. In this
monograph, we discuss the current status of ROS
and AO systems and their influence on the
periodontal disease. (6)
Reactive oxygen species: The various true
radicals and reactive oxygen species (ROS) and
their symbols have been summarized in Table 1
RADICALS

NON- RADICALS

1
Superoxide
O2 .Singlet oxygen
O2
Hydroxyl
OH.
Ozone
O3
Hydroperoxyl
HOO Hypochlorous acid
HOCl
Alkoxyl
RO.
Hydrogen peroxide
H2 O 2
Aryloxyl
ArO .
Arylperoxyl
ArOO.
Peroxyl
ROO .
Acyloxyl
RCOO .
Acylperoxyl
RCOOO
T able 1 Origin and formation of ROS and oxygen
radicals(4)

Exogenous source are heat, trauma,


ultrasound, ultraviolet light, ozone, smo king,
exhaust fumes, radiation, infect ion, excessive
exercise and therapeutic drugs.(7)
Endogenous source(7) which result in
formation of ROS include:a.

b.

Bi-products of metabolic pathways:- During cell


metabolism, electrons leak from their transporters
at a constant rate during the process of glycolysis,
reducing oxygen to superoxide anion.
ROS can also be generated by phagocytes and
cells of the connective tissue. The process
comprises the respiratory burst and is stimulated
by a variety of mitogens or antigens. (8)

Mechanisms of Tissue Damage


The reactive o xygen species may cause
damage to various cellular and extracellu lar
tissues by targeting the following substances:

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1.

2.

3.

INTERNATIONAL JOURNAL OF DENTAL CLINICS 2011:3(2): 44-47

Protein damage: It results in fragmentation and


polymerization reactions of various protein
molecules leading to the formation of protein
radicals and protein-bound ROS.(8)
Lipid peroxidation: It is one of the most
important reactions of free radical species.
Hydroxyl and peroxynitrate anion are most
effective in activating this process. (9)
DNA damage: The mechanism of DNA damage
by peroxynitrate and hydroxyl radical include;
Strand breaks, Base pair mutations, Deletions,
Insertions,
Nicking
and
Sequence
amplifications.(10)

Evidence for the Presence and Role of Ross


in Periodontal Tissue Damage: Halliwell
proposed four criteria, similar to that proposed
by Robert Koch in 1884, to establish causal
relationship between an organism and disease.(7)
1.
2.

3.

4.

ROS or the oxidative damage caused must be


present at the site of injury.
The time course of ROS formation or the
oxidative damage caused should occur before or
at the same time as tissue injury.
Direct application of ROS over a relevant time
course to tissues at concentrations found in vivo
should reproduce damage similar to that observed
in the diseased tissue.
Removing or inhibiting ROS formation should
decrease tissue damage to an extent related to
their antioxidant action in vivo.

In
patients
with
early
onset
periodontitis, low superoxide production is seen
after fM LP stimu lus of blood neutrophils. Even
in patients with adult periodontitis, increased
generation of free o xygen radicals and increased
ratio between released elastase and lactoferrin is
seen in peripheral neutrophils thus causing tissue
destruction. (7)
Enhanced ROS generation by peripheral
neutrophils fro m patients with both chronic and
aggressive disease has been shown to be
stimulated with opsonized bacteria associated
periodontal disease (Fusobacterium nucleatum,
Actinobacillus actinomycetemcomitans). This
finding suggests that the hyper active phenotype
of peripheral neutrophils could have local tissue
damaging consequences.(11)
Myeloperoxidase is released into the
phagosome
and
extracellularly
during
phagocytosis and activation of neutrophils when
it is important for generating hypochlorous acid
and other ROS. Raised levels o f all three fo rms
of myelopero xidases in g ingival crevicu lar fluid
fro m diseased sites have been reported in
gingivitis, chronic periodontitis (12), rapidly
progressive periodontitis, localized juvenile
periodontitis and aggressive periodontitis. These
studies have demonstrated a relationship between

INT ERNA TIONA L JOURNA L OF D ENT AL CL IN ICS

gingival
crev icular
fluid
level
of
myelopero xidases and clinical measures of the
disease and that the levels reduce after
treatment.(13)
Smoking, which is an important risk
factor for periodontitis, induces oxidative stress
in the body and causes an imbalance between
reactive o xygen species (ROS) and antio xidants,
such as superoxide dis mutase (SOD). A
progressive reduction in SOD levels has been
seen from healthy non-smokers to light smo kers
to heavy smokers, thus highlighting the role of
oxidative stress in causing periodontal disease in
smokers.(14)
Effects of ROS on Periodontal Tissues and
Components: The reactive o xygen species cause
periodontal tissue damage by,
1.
2.
3.
4.

5.

Ground substance degradation


Collagenolysis either directly or indirectly or as a
result of oxidation of proteases
Stimulation of excessive pro-inflammatory
cytokine release through NF-B activation
PG-E2 production via lipid peroxidation and
superoxide release, both of which have been
linked with bone resorption
Since IL-1 & TNF- positively regulate their own
production, the additive effects of endotoxinmediated cytokine production and that arising
from respiratory burst of PM NLs in response to
the same organisms, lead to periodontal
inflammation and subsequent attachment loss.(7)

Thus role of reactive oxygen species on


periodontal tissue can be summarized as shown
in the figure 1. While most ROS have ext remely
short half-lives, they can cause substantial tissue
damage by initiat ing free radical chain reactions.
Therefore the body contains a number of
protective antioxidant mechanis ms, whose
specific role is to remove harmfu l o xidants
(ROS) as soon as they form or to repair damage
caused by ROS in vivo.
Antioxidants are defined as those
substances which when present at low
concentrations, compared to an oxid isable
substrate, will significantly delay or inhibit
oxidation of that substrate.(15) The various
antioxidants are discussed below.
Antioxidants can be categorized by
several methods:
I. According to their mode of action:Preventative

Scavenging

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Enzymes- superoxide dismutase, catalase,


glutathione peroxidase, DNA repair
enzymes.
Metal
ion
sequestrators- albumin,
lactoferrin, transferrin, ceruloplasmin, uric
acid, Polyphenolic flavenoids
Ascorbate, Carotenoids, uric acid, vitamin
E, bilirubin, reduced glutathione & other
thiols

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INTERNATIONAL JOURNAL OF DENTAL CLINICS 2011:3(2): 44-47

II. According to their location:Intracellular


Extracellular

Membrane
associated

Superoxide dismutase enzymes-1& 2,


catalase, glutathione peroxidase, DNA
repair enzymes & reduced glutathione.
Superoxide dismutase enzyme-3, selenium
glutathione
peroxidase,
reduced
glutathuione,
-tocopherol

III. According to their solubility:Water


soluble

Lipid soluble

Haptoglobin,
ceruloplasmin,
albumin,
ascorbate,
uric
acid,
Polyphenolic
flavenoids, reduced glutathione & other
thiols, cysteine & transferring
-tocopherol,
Carotenoids,
bilirubin,
quinones

Ascorbic: Ascorbic acid is the only


endogenous antioxidant in p lasma that can
completely protect against peroxidative damage
induced by the oxidants released from activated
neutrophils. The protection is provided by
scavenging superoxide and peroxyl radicals and
decrease the pro-inflammatory gene expression
via effects on nuclear factor B transcription
factor.(16)
- Tocopherol (Vitamin E) is generally
regarded as the most important and effect ive
lip id soluble anti-o xidant in vivo. It is vital in
maintaining cell memb rane integrity against lipid
peroxidation by peroxyl radical scavenging. Its
antioxidant behavior is the result of a single
phenolic OH group, which when o xid ized gives
rise to vitamin E radical.(7)
Carotenoids provide protection by
formation of singlet o xygen and pero xyl radical.
Carotenoids are derived only fro m d iet (green
vegetables,
tomatoes,
fruits),
lycopene
predominates in plas ma, with to matoes being the

main dietary source in humans (other sources


include red grapefruits & water melon).(7)
Co-Enzyme Q10 exists in an oxid ized form
(ubiquinone or CoQ) and a reduced form
(ubiquinol or CoQH2 ), both of which possess
anti-o xidant activity. Co Q10 is also regarded as a
pro-o xidant molecule in response to various
pathophysiological events.(17)
Polyphenols (Polyphenolic flavonoids)
are absorbed following dietary intake of
vegetables, red wine and tea. The cellu lar
mechanis ms involved in FR/ROS protection is
mainly due to their direct antioxidant properties
(e.g. by sparing vitamin E or by regenerating
vitamin C) o r to their inhibitory activity towards
lipooxygenase.(18)
Glutathione plays a majo r ro le in
maintaining the intracellu lar redo x balance and
thus regulating signaling pathways which are
affected by oxidative stress.(19)
Lazaroids are 21-aminosteroids. They
are a newly identified family of co mpounds
whuch are derived fro m glucocorticoids, but lack
both glucocorticoid and mineralocorticoid
activities. These compounds scavenge lipid
peroxy l radicals and inhibit iron-dependent lipid
peroxidation by a mechanis m similar to that of
vitamin E.(7)
Conclusion
The following points can be concluded at
the current time with respect to reactive o xygen
species and antioxidants in periodontics
1.

Reactive oxygen species cause periodontal tissue


destruction either by degrading the ground
substance or by release of collagenases or by
release of various inflammatory mediators.

Periodontal pathogens
LPS
DNA
Osteoclast
activation

Cell wall components

Junctional
epithelium & other
PDL cells

Release of
inflammatory
cytokines &
chemokines

Fibroblast
generation of ROS
O XIDATIVE
STRESS

PMNL generation of ROS

Recruitment &
activation of
hyperresponsive
PMNs

Release of various inflammatory mediators


& generation of ROS

T issue damage

Figure 1 Role of reactive oxygen species Antioxidants

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INTERNATIONAL JOURNAL OF DENTAL CLINICS 2011:3(2): 44-47

2.

Antioxidants remove these harmful oxidants


10. Takane M , Sugano N, Iwasaki H, Iwano Y,
(reactive oxygen species) as soon as they form or
Shimizu N, Ito K. New biomarker evidence of
repair the damage caused by ROS in vivo.
oxidative DNA damage in whole saliva from
3. A delicate balance exists between antioxidant
clinically healthy and periodontally diseased
defense and repair systems and pro-oxidant
individuals. Journal of Periodontology. 2002;
mechanism of tissue destruction which if tipped
73(5):551-4.
in favour of tissue damage, could lead to
11. Whyte G, Seymour GJ, Cheung K, Robinson M F.
significant attachment loss.
Chemiluminescence
of
peripheral
4. This array of pathways in periodontal tissue
polymorphonuclear leukocytes from adult
destruction provides opportunities to develop
periodontitis patients. Journal of Clinical
novel antioxidant therapies.
Periodontology. 1989;16(2):69-74.
5. However, definitive involvement of this ROS and
12. Cao.C,
Smith.Q.
Crevicular
fluid
reduced antioxidant activities has not yet been
myeloperoxidase at healthy, gingivitis and
established and further studies are required.
periodontitis sites.
Journal of
Clinical
Affiliations of Authors: 1. Dr. Alok Sharma, M .D.S,
Periodontology. 1989;16(1):17-20.
Senior Lecturer, Department of Prosthodontics, Jaipur
13. Battino M , Bullon P, Wilson M , Newman H.
Dental College, 2. Dr. Swati Sharma,M .D.S, Senior
Oxidative injury and inflammatory periodontal
Lecturer, Department of Periodontics, M ahatma
diseases: the challenge of anti-oxidants to free
Gandhi Dental College and hospital, Jaipur, Rajasthan,
radicals and reactive oxygen species. Critical
India.
Reviews in Oral Biology and M edicine. 1999;
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E-mail: draloksharmamds@gmail.com
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Source of Support: Nil, Conflict of Interest: None Declared

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