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Attia A M, Edrees M F, Alghriany A. Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to
nonsurgical periodontal therapy in chronic periodontitis patients. J Periodontal Med Clin Prac 2016;03: 128- 140
1 2 3Dr. Alaa Moustafa Attia , Dr. Mohamed Fouad Edrees , Dr. Alzahraa Alghriany
Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal
therapy in chronic periodontitis patients
Original Research
Affiliation
1. Dr. Alaa Moustafa Attia- Associate Professor Oral Medicine and Periodontology, Faculty of
Dentistry, Al-Azhar University (Assiut Branch), Egypt and Umm Alqura University, KSA.
2. Dr. Mohamed Fouad Edrees- Lecturer Oral Medicine and Periodontology, Faculty of Dentistry, Al-
Azhar University (Assiut Branch).
3. Dr. Alzahraa Alghriany- Assistant Lecturer Oral Medicine and Periodontology, Faculty of Dentistry,
Assuit University.
Corresponding Author:
Name: Dr Alaa Moustafa Attia
Address: College of Dentistry, Umm Alqura University, Makah, Saudia Arabia
Email Address: [email protected]
128
Abstract:
Background:Periodontal pathogens can induce
overproduction of free radicals and reactive
oxygen species (ROS)that may increase
periodontal tissue breakdown. Coenzyme Q10
(CoQ10) serves as potent endogenous antioxidant
that act as a scavenger to ROS and may be suppress
the periodontal inflammation.
Aim:The present study was aimed to evaluate the
clinical and immunologic effects of intrapocket
application of CoQ10 as an adjunct to nonsurgical
periodontal therapy.
Materials and methods:Twenty eight mild to
moderate chronic periodontitis patients with age
ranged from 29 to 46 years. All individuals were
carried out to scaling and root planning (SRP) and
classified into group 1 (G1, treated by SRP only)
and group 2 (G2, treated by COQ10 gel plus SRP).
Clinical parameters; plaque index (PI), gingival
index (GI), pocket depth (PD) and clinical
attachment loss (CAL), in addition to gingival
crevicularfluid (GCF) samples were obtained at
baseline and 30days after treatment. Tumor
necrosis factor- (TNF-) levels were evaluated by
ELISA technique at both time intervals of
periodontal therapy.
Results: Clinical evaluation of both groups
revealed a high significant improvement in all
parameters at baseline and 30 days of treatment
(P≤0.01). Whereas, more clinical improvement in
G2 at 30 days compared to G1, but the difference
was non-significant (P≥0.05). TNF- levels were
significantly high reduced at 30 days versus to
baseline in both groups (P≤0.01), in comparison
between groups at 30 days TNF- levels reduced in
G2 compared to G1, but there is no significant
difference (P≥0.05).
Conclusions:Topical application of CoQ10 as an
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
adjunct to non-surgical periodontal therapy
improve the clinical and immunologic findings, but
it not considered a significantadjunct modality for
periodontal therapy. Further studies needed to
clarify clinical and immunological outcomes.
Keywords: chronic periodontitis, non surgical
therapy, host response
Introduction:
Chronic 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 ultimately results in tooth loss. It can be
defined as a chronic infectionthat results from the
interaction of periodontopathogenic bacteria and 1host inflammatory immune responses.
Coenzyme Q10 (CoQ10) belongs to a homologous
series of compounds that share a common
benzoquinone ring structure but differ in the length
of the isoprenoid side chain. In humans and a few
other mammalian species, the side chain is
comprised of 10 isoprene units. Also, CoQ10 is 2similar to vitamin K in its chemical structure.
CoQ10 is considered as an antioxidant, so that it is
essential for the health of virtually all human tissue 3 and organs. Itis also known to play a crucial role in
the generation of adenosine triphosphate (ATP)
and cellular respiration, and act as a primary
scavenger of free radicals (FRs) and reactive 4oxygen species (ROS).
Healing and repair of periodontal tissues requires
efficient energy production, which depends in part
on an adequate supply of CoQ10. Gingival biopsies
revealed subnormal tissue levels of CoQ10 in 60%
to 96 % patients with periodontal disease and low
levels of CoQ10 in leukocytes in 86% of cases.
These findings indicate that periodontal disease is 5frequently associated with CoQ10 deficiency.
Many clinical trials with oral administration of
CoQ10 to patients with periodontal disease have
been conducted. The results have shown that oral
administration of CoQ10 increases the
concentration of CoQ10 in the diseased gingiva
and effectively suppresses advanced periodontal 6,7,8inflammation and periodontal microorganisms.
Topical application of CoQ to the periodontal 10
pocket was evaluated with and without subgingival
mechanical debridement. In the first three-week
period, significant reduction in gingival crevicular
fluid flow, probing depth and attachment loss were
found and significant improvements in modified
gingival index, bleeding on probing and peptidase
activity derived from periodontopathic bacteria
were observed only at experimental sites which
treated CoQ10 with subgingival mechanical 9debridement.
A study on clinical evaluation of topical application
of the Perio-Q gel (Coenzyme Q10) in chronic
periodontitis patients.The results represented that
intra-pocket gel application in combination with
scaling and root planning (SRP) showed
significant reduction (P<0.05) for plaque index
(PI), gingival index (GI), gingival bleeding index
(GBI), and clinical attachment loss (CAL) in
comparison to intra-pocket gel alone. On the other
hand, sub-gingival mechanical debridement only
and with CoQ10 (Perio-Q gel)showed almost
similar clinical results without any statistically 10 significant differences. Moreover, coenzyme Q10
can be said to have a beneficial effect clinically on
gingivitis and slight periodontitis when used as 11adjunct to scaling and root planning.
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
Raut and Sethi 2016 performed a comparative
study on the efficacy of Coenzyme Q10 and tea tree
oil gel as an adjunct to scaling and root planing in
the treatment of chronic periodontitis. They
concluded that Coenzyme Q10 and tea tree oil gel
proved to be effective in the treatment of chronic 12periodontitis.
TNF-α is an proinflammatory cytokine that plays a
role in the development and maintenance of
inflammatory diseases, its mediating effects on the
development, progress, and maintenance of 13periodontal diseases would be expected to occur.
The effect of oral administration of coenzyme Q10
on the levels of tumor necrosis factor-α(TNF-α)
and interleukin-10 (IL-10) in gingival tissue of
experimental periodontitis in rats was studied by.
They reported that Coenzyme Q10 inhibits the
expression of TNF-α and promotes the expression
of IL-10 in periodontal tissues of experimental
periodontitis rats. Coenzyme Q10 may play a role 14in treating periodontitis.
Hence, the aim of the present study was to evaluate
the intrapocket application of Coenzyme Q10 in
nonsurgical periodontally treated chronic
periodontitis patient to assess of clinical outcomes
and the changes in gingival crevicular fluid (GCF)–
TNF- levels.
Materials and methods:
Patients:Twenty eight patients of both sex (18
females and10 males) ranged in age from 29-46
years with a mean of 38 ± 60 years with mild to
moderate chronic periodontitis. All subjects were
selected from patients attending at the out-patient
clinic, Oral Medicine and Periodontology
Department, Faculty of Dental Medicine, Al-Azhar
University, Assiut Branch. A clinical examination
was done to all patients participate in the study, and
patients gave their agreement.
All patients were categorized into two groups:
Group I: It includes 14 chronic periodontitis
patients were treated by conventional periodontal
therapy alone (scaling and root planning).
Group II: It includes 14 chronic periodontitis
patients were treated by conventional periodontal
therapy with intrapocket and topical application of
coenzyme Q 10.
Selection of patients: The inclusion criteria
include the following:
1- All subjects were free from any systemic
diseases according to the criteria of Modified 15 Cornell Medical Index.
2- All subjects were not receiving antibiotics and
non-steroidal anti-inflammatory for at least three
months prior to sample collection.
3- All subjects were non-smokers and cooperative.
4-All subjects were suffering from chronic
periodontitis with pocket depth not more than 6
mm and clinical attachment level (CAL) not more
than 4 mm.
5- All subjects were not subjected to previous
periodontal therapy during at least 6 months.
6- All subjects were not receiving vitamin
supplements. 7- All Subjects were not regularly
using mouth washes.
Periodontal examination: The periodontal
conditions were evaluated for all subjects for
baseline and 30 days using following parameters:
Plaque Index (PI), Gingival index (BI), Pocket 16-19depth (PD) and Clinical attachment loss (CAL).
Periodontal therapy:All individuals were carried
out to nonsurgical periodontal treatment include;
scaling and root planning (SRP) that done through
3 visits and the patient became maintained on
plaque control measures. Fig (1,3)
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
GCF samples co1llection:GCF samples were
obtained from all patients. The site which showed
the highest probing depth and CAL (range 4-6 mm)
score was selected for GCF sampling. The teeth
selected for sampling was isolated with cotton roll,
and supragingival plaque was removed without
touching the marginal gingiva. The crevicular site
was then dried gently with an air syringe. Samples
of GCF were obtained before probing into the site
by placing paper point. Sterilized paper point size #
30was carefully inserted to the maximum depth of
the periodontal pocket and held in position for 30 20second. The site that did not express any volume
of GCF, and paper point which were contaminated
with blood and saliva, were excluded from the
study. The collected GCF was immediately
transferred into plastic vials containing phosphate
buffer saline (PBS) and the samples were frozen at -
70° C till they were assayed for TNF-α.
Application of Coenzyme Q10:In patients of the
Group 2 after treatment with conventional
periodontal therapy the teeth isolated by cotton
rolls for intrapocket and topical application of ®Perio-Qgel (PERIOQ INC, Manchester, USA). It
is a mixture of CoQ10 in a vegetable oil base in a
ratio of 1:9. It is supplied as a pack of gel and was
stored at a temperature between 4°C and 8°C for
maintaining its shelf-life.
The periodontal pocket was dried with paper points
before subgingival administration of Perio- Q gel.
Intrapocketapplication of gel with bunted needle
tip, eating, spitting and drinking was restricted for 1
hour after application, teeth brushing and flossing
for 4 hours after application. Patients were
instructed for plaque control regimen, and the oral
hygiene instructions were provided at each
appointment. Topical application was repeated
after7 &15 days. (Fig 2)
TNF-α ELISA Assay:The samples were assayed
for TNF-α levels using commercially available
enzyme-linked immunosorbent assay (ELISA).
The assay was conducted according to the
manufacturer's instructions. Highly sensitive
ELISA kit (Shanghai Sunred Biological
Technology Co., Ltd) was used to detect the TNF-α
level in the sample of Human serum, blood plasma,
GCF and other related tissue liquid.
Statistical analysis:The results were recorded and
statistically analyzed using Statistical Package for
Social Science (SPSS Version 22, IBM Inc,
Chicago, IL, USA). P < 0.05 was defined as
statistically significant. The tables and figures were
done by Microsoft word 10.
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
Fig (1): Group 2 female 41 aged patient before treatment.
Fig (2): Intrapocket application of CoQ10 gel
Fig (3): Patient at 30 days after treatment
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
Results:
Twenty eight patients suffering from mild to
moderate chronic periodontitis with probing
pocket depth 4-6 mm and CAL not more than 4
mm. The patients were divided into two groups:
Group 1 (G1) treated by scaling and root planning
(SRP) only, and group 2 (G2) treated by SRP plus
topical and intrapocket application of Coenzyme
Q10 gel. The clinical outcomes of periodontal
parameters and levels of GCF-TNF- were assessed
at baseline and 30 days after treatment.
Clinical findings:The results of mean values of PI,
GI, PD and CAL among both groups at baseline
and 30 days showed high statistically significant
differences (P<0.01). (Table 1, Fig 4,5)
Table 2 showed independent t-test for comparing
Means, Standard deviations, t values and p-values
among the two groups at baseline and 30 days
representing an improvement in G2 versus G1. The
statistical comparison revealed that no statistical
significant difference in G2 compared with
G1(P≥0.5).
TNF-alpha assaying: The mean values, Standard
deviations, t values and p-values records were
expressed in (Table 3, Fig 6).The statistical
comparisons between the baseline and 30 days for
both groups, the differences were highly
significant (P<0.01).
The statistical comparisons between both groups at
baseline and 30 days were revealed in (Table 3), the
statistical results were represented a reduction of
TNF- levels at 30 days in both groups. The levels of
TNF-more decreased in G2 than G1 at day 30,
while, the statistical differences were non-
significant (P≥0.5).
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
Table (1): Demonstrate the statistical comparisons of clinical parameters at baseline
compared to 30 days in both groups.
G1= Treated by SRP only G2= Treated by SRP and CoQ10 application
PI= Plaque index GI= Gingival index
PD= Pocket depth CAL= Clinical attachment loss
** = High significant (P= 0.01)
Table (2): Show the statistical comparisons of clinical parameters at 30 days in both
studied groups.
G1 = Treated by SRP only G2= Treated by SRP and CoQ10 application
PI= Plaque index GI= Gingival index
PD= Pocket depth CAL- Clinical attachment loss
Baseline 30 Days T Value P Value
G1 PI 2.69±0.480 1.23±0.43 6.789 ٠.٠٠٠**
G I 2.36±0.275 0.85±0.16 23.739 0.000**
PD 4.27±0.436 3.55±0.39 5.269 0.000**
CAL 2.33±0.473 1.83±0.36 6.059 0.000**
G2 PI 2.68±0.470 1.15±0.37 10.690 0.000**
G I 2.32±0.249 0.80±0.32 13.056 0.000**
PD 4.22±0.364 3.32±0.30 7.831 0.000**
CAL 2.35±0.962 1.70±0.39 6.150 0.000**
Comparison Mean ± Sd T V alue P Value
PI G1 Vs G2
At 30 days
G1 (1.23±0.43)
G2 (1.15±0.37)
0.480 0.635
G I G1 Vs G2 G1 (0.85±0.16 )
G2 (0.80±0.32)
0.530 0.601
PD G1 Vs G2 G1 (3.55±0.39)
G2 (3.32±0.30)
1.696 0.103
CAL G1 Vs G2 G1 (1.83±0.36)
G2 (1.70±0.39)
1.032 0.312
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
Table (3): Revealed the statistical comparisons of GCF - TNF-c � (Pg1k j' � jct cjq� gl �
both studied groups.
G1 = Treated by SRP only G2= Treated by SRP and CoQ10 application
** = High significant (P= 0.01)
Comparisons Mean±Sd T Value P Value
G1 Baseline 319.90±30.699 3.941 ٠.٠٠٢**
30 days 281.67±46.089
G2 Baseline 322.48±49.223 12.710 0.003**
30 days 278.85± 52.329
G2 Vs G1 Baseline 322.48±49.223 1.179 0.249
Baseline 319.9±30.699
G2 Vs G1 30 days 278.85± 52.329 - 2.702 0.062
30 days 281.67±46.089
Discussion:
Chronic Periodontitis is an inflammatory process,
initiated by the plaque biofilm, which leads to loss
of periodontal attachment to the root surface and
adjacent alveolar bone that result from the
interaction of perio-pathogens and host
inflammatory immune responses. It is considered
as one of the most common bacterial infection
worldwide with prevalence in mild to moderate
forms ranging from 13% to 57% in different
populations depending on oral hygiene and socio-21
economic status.
Periodontal pathogens can induce reactive oxygen
species (ROS) overproduction and thus may cause
collagen and periodontal cell breakdown. When
ROS are scavenged by antioxidants, there can be a
reduction of collagen degradation. Ubiquinol
(reduced form coenzyme Q10) serves as an
endogenous antioxidant which increases the
concentration of CoQ10 in the diseased gingiva and
effectively suppresses advanced periodontal 22inflammation.
A deficiency of CoQ10 at its enzyme sites in
gingival tissue may exist independently of and/or
because of periodontal disease. If a deficiency of
CoQ10 expressed in gingival tissue for nutritional
causes and independently of periodontal disease,
then the advent of periodontal disease could
enhance the gingival deficiency of CoQ10. In such
patients, oral dental treatment and oral hygiene
could correct the plaque and calculus, but not that
part of the deficiency of CoQ10 due to systemic
cause; therapy with CoQ10 can be included with
the oral hygiene for an improved treatment of this 23type of periodontal disease.
On exogenous CoQ10 administration, an increase
in the specific activity of this mitochondrial
enzyme was found in deficient patients. The
periodontal scores were also decreased concluding
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
that CoQ10 should be considered as an adjunct for
the treatment of periodontitis in current dental 6
practice.
The purpose of this study was to evaluate the
clinical and immunologic efficacy of topically
applied CoQ10 as an adjunct to basic conventional
therapy in treatment of mild to moderate chronic
per iodont i t i s .The local appl ica t ion of
chemotherapeutic agents into periodontal pocket
could be beneficial, both in terms of rising drug
concentration directly in the active site, and in 24
preventing systemic side effects.
About 20%–30% of all chronic periodontitis cases
do not respond favorably to conventional
periodontal treatment. Many factors may
contribute to that response, such as improper
removal of bacterial deposits and calculus, poor
plaque control, systemic conditions leading to an
impaired immune response, defective restorations,
occlusal dysfunction, periodontal-endodontic
involvement and others. In these cases, other 23
treatment approaches.
The present study aimed to use a new modality in
the periodontal therapy by topical application of
antioxidant as adjunctive to basic conventional
therapy to overcome the unresponsive cases
treated by conventional periodontal therapy alone.
In the resent study, there is a highly significant
reduction of clinical parameters in patients treated
by CoQ10 plus SRP and patient treated by SRP
only. These findings were in accordance to several 6,9,10,12
studies. On the other hand, when comparing
the mean values of clinical parameters after
treatment at 30 days between both groups more
reduction was seen in patients treated by CoQ10
but the statistical differences was non-significant.
This results in consistent with Sale et al. 26
2014 whereas our results in contrary with findings 10
of Hans et al. 2012 , they reported that intra-
pocket gel application in combination with SRP
showed significant reduction (P<0.05) for PI, GI,
GBI, and CAL in comparisons to sites treated by
SRP only.
Therefore, the effect of CoQ10 locally may be not
enough to provide a significant effect than SRP
only due to deficiency of CoQ10 in the periodontal
tissues, this concept is supported by some 6,23
studies.
The mean values of GCF- TNF-α levels compared
among both groups at baseline, and 30 days
showed marked decrease in level of TNF-α (highly
significant difference) in both groups at 30 days
when compared to the baseline this is in agreement 28
with the finding of Heralgi et al. 2011 who found
that the severity of inflammation increases, there is
a significant increase in the TNF-α level
suggesting that there is a direct relationship
between TNF-α level in GCF and periodontal
destruction proved thatTNF-α may be used as a
potential biochemical marker for assessment of
periodontal disease activity in chronic generalized
periodontitis.
29In a study done by Aditietet al.2013 determined
uric acid level as anantioxidant in patients with
chronic periodontitis treated with topical
antioxidants predicting that with the improvement
of the periodontal tissue inflammation the
antioxidants level will raise so uric acid level will
increase. This direct indicator may give a false
diagnosis with many factors as any food,drink or
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Clinical and immunological evaluation of Coenzyme Q10 as an adjunct to nonsurgical periodontal therapy in chronic periodontitis patients
any other supplement contains antioxidants that
may raise the GCF uric acid level. TNF-α was
chosen in this study as an indirect indicator to the
response of the periodontal tissue to CoQ10
antioxidant in treatment of chronic periodontitis.
TNF-α level was high at baseline before the
treatment with SRP and CoQ10gel this level was
decreased in further session with a significant
improvement in periodontal tissue and significant
difference in periodontal parameters confirmed that
there was increase in antioxidant level and its
balance with ROS was regain, these could be 30attributed to Chapple et al.2007 who mentioned
that loss of balance between ROS and antioxidant
defense has been implicated as an etiological factor
for periodontal diseases that may manifested as an
increase in oxidative stress or decrease in individual
antioxidant level.
For elucidation, why the levels of TNF- not
significantly reduced at 30 days of treatment in G2
(SRP plus CoQ10) versus G1 (SRP only), this may
be related to the deficiency of endogenous CoQ10
that reduce ROS which induce periodontal
inflammation. This explanation supported by an
experimental study on the effect of oral
administration of CoQ10 on the expression of
tumor necrosis factor-α and interleukin-10 in
gingival tissue of experimental periodontitis in 14rats. They concluded that the CoQ10 inhibits the
expression of TNF-α and promotes the expression
of IL-10 in periodontal tissues of experimental
periodontitis rats. Regarding to that result, the
CoQ10 may play a role in treating periodontitis.
Periodontal condition after oral applications of
CoQ10 with vitamin E was studied by Brzozowska 27et al. 2007 , they concluded that CoQ10 with
vitamin E had a beneficial effect on the periodontal
tissue.
Based on suggestion of previous studies, the oral
administration plus topical application of CoQ10
gel may be more beneficial to diseased periodontal
tissues through reducing the Levels of TNF- and
improvement the clinical outcomes of periodontal
therapy. So that, the systemic and local
adminstrition of CoQ10 may be may an interest
scientific point of research.
In conclusions, the topical application of CoQ10 as
an adjunct to non-surgical periodontal therapy
improve the clinical and immunologic outcomes,
but it not considered a strong modality for
periodontal therapy. Tumor Necrosis Factor- α
could be considered as strong laboratorymarker for
periodontal disease activity. In addition,
conventional periodontal therapy remains the
cornerstone as basicand initial periodontal therapy.
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Competing interest / Conflict of interest The author(s) have no competing interests for financial support, publication of this research, patents and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript.Source of support: NIL
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