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Oxygen Consumption of Gingiva – An Update

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Review Article Dental & Oral Health International Journal
Oxygen Consumption of Gingiva – An Update

Rudrakshi C*, M L V Prabhuji and Ashwin P S

1. Reader, Department of Periodontology, Krishnadevaraya College of Dental Sciences & Hospital, Bengaluru.
2. Professor & Head of the Department, Department of Periodontology, Krishnadevaraya College of Dental Sciences & Hospital, Bengaluru.
3. Post Graduate Student, Department of Periodontology, Krishnadevaraya College of Dental Sciences & Hospital, Bengaluru.

*
Corresponding author
Dr. Rudrakshi C, MDS, Reader, Department of Periodontology, Krishnadevaraya College of Dental Sciences & Hospital, Bengaluru.
E-mail: drrudrakshi@rediffmail.com, Ph: +91-9986110826
Submitted: 7 Nov 2019 Accepted: 15 Nov 2019 Published: 23 Nov 2019

Abstract
The oxygen metabolism of gingiva remains an important, yet unexplored phenomenon. The literature present on this subject is scanty and to some
extent, indirect. The Histochemistry of gingiva has been looked into at depth and various enzymes and biochemical pathways have been identified
which are important for gingival homeostasis. This review summarizes and is an attempt to co-relate oxygen metabolism fluctuations and gingival
pathologies, and whether its stabilization could be a possible treatment.

Keywords
Periodontitis, Gingivitis, Tissue oxygenation
Introduction
When we took our first step into the world of science and biology, we were
taught that all living things breathe and to do so they require – Oxygen, the
very mention of which signifies life. Our researchers have successfully
contributed to discovering the microbiological, immunological,
histochemical aspects of the periodontium which has helped us in their
application, for the diagnoses and treatment of various pathologies of the
periodontium. However to understand the metabolism of a living tissue in
totality, there is another aspect of it that needs to be looked into and that
is the biochemistry.
The oxidative metabolism of gingiva also, is an important part of the
gingival biochemistry which includes various anabolic and catabolic
reactions taking place at the tissue level that requires oxygen. Adapation
to a reduced oxygen supply maintain immune cell surveillance capacity
in all tissue environments. This is important and necessary for successful
elimination of pathogens [1].
blood contains about 15 gm of Hb). When the O2 at the tissue level falls,
the O2 from Hb dissociates, and gets replenished in the tissues. HbO2 is a
sort of reserve sink.
Some issues regarding O2, delivery in the tissues:
The single most important factor regarding O2 delivery in the tissues is,
the distance between the capillaries and the cells (cells which are target for
O2). When this distance increases, the O2 delivery decreases.
One of the ways by which nature meets these challenges is by increasing
the number of capillaries (one of the features of an inflammatory state).
Unloading of O2, in the Tissues:
In the tissues, O2 is unloaded where the vessel wall is thin like the capillaries
and not where the vessel wall is thick like the arteries.
Coefficient of Utilization:

Few decades back, an important relationship had been postulated between

the oxygen consumption by the gingival tissues and its health, the
understanding of which requires the understanding of various metabolic
pathways at tissue level.

Why Oxygen? Tissue Survival

Tissues of our body utilize oxygen for metabolic purposes and produce
carbon dioxide as a result of metabolism. At the tissue level, the blood
discharges (delivers) oxygen to the tissues, where the oxygen is utilized
for various purposes.
Oxygen and Hemoglobin (Hb) can combine with O2. The maximum
amount of O2 that can be bound by Hb present in 100 ml of blood in a
given person is called the O2 capacity of that given person (100 ml of
Dental & Oral health Int. Journal, 2019
If the delivery of O2, to the tissue begins to fall, intensity of the tissue
metabolism and requirement remains same, then the Ptiss O falls and
cellular death occurs.
Catabolism and Energy Production
Catabolism is an important component of metabolism and occurs in
the stages which may be simplified as: carbohydrate, fat and protein
monosaccharide, fatty acids, glycerol and amino acids. Pyruvate, Acetyl
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CoA, which are the main fuel for the citrate cycle which is as follows:
It may be emphasized that it is the utilization of hydrogen and not the
production of carbon dioxide which is the decisive energy yielding
process and the one which requires respiratory oxygen. Dehydrogenation
reactions cause a pair of hydrogen atoms to be released. These are picked
up by special hydrogen carriers (example Ubiquinone Q10 or Coenzyme
Q) [2].
Oxygen, Mitochondria and Gingiva: The terminal stages of catabolism,
including the major oxidative reactions that produce about 95% of the
total ATP is, the process by which pyruvate is converted into acetyl-CoA
which is then caught up into the reactions of the citrate cycle and the
respiratory chain, all takes place within the mitochondria. In the gingiva,
cytoplasmic organelle concentration varies among different epithelial
strata: Mitochondria are more numerous in deeper strata and decrease
toward the surface of the cell. Accordingly, histochemical demonstration
of succinic dehydrogenase, NAD, cytochrome oxidase, and other
mitochondrial enzymes revealed a more active tricarboxylic cycle in basal
and parabasal cells where the proximity of the blood supply facilitates
energy production through aerobic glycolysis and hence implies more
oxygen consumption compared upper layers of the gingival epithelium.
Conversely, enzymes of the pentose shunt (an alternative pathway of
glycolysis), such as glucose-6-phosphatase, increase their activity towards
the surface and its intermediate products can be used for the synthesis
of keratinization proteins. (i.e., products of Krebs cycle, which requires
oxygen are not required for keratinization or oxygen consumption would
not directly affect the gingival keratinization).
Oxygen Metabolism, The Pathogenesis, Development and
Therapy of Periodontal Diseases - Is There A Connection?
Against the background that microbial activities of PMN
(Polymorphonuclear leucocytes) cells are strongly dependent upon certain
of their oxidative metabolic processes and that a strong relationship exists
between the abnormalities of PMN function and periodontal diseases.
There now emerges for renewed consideration the question of the
oxidative metabolism of the host gingival tissues which provides the arena
or setting for the critical battles between PMNs and micro-organism and
ask whether gingival tissue oxidative metabolism per se, may also be of
importance in the pathogenesis, development and therapy of periodontal
diseases.
A low pO2 environment facilitates certain periodontopathogens to do
more harm to the host than their action as mediators of inflammation. P.
gingivalis is one such periodntopathogen that increases PDL fibroblasts’
oxidative stress and induces a reduction of catalase indicating a collapse
of protective machinery favouring increase in reactive oxygen species and
progression of inflammatory oral diseases [3].
As per the study [4] by Liu K- Z et al tissue oxygen saturation was
significantly decreased in the gingivitis and periodontitis sites, compared
to the healthy sites. There was a trend towards increased concentration of
Hb and decreased concentration of HbO2 from healthy to diseased sites.
Zhang et al [5] used optical spectroscopy to assess tissue oxygenation in
individuals suffering from coronary artery diseases and noted that tissue
oxygen saturation was significantly decreased in the periodontitis sites
compared to the healthy sites in those individuals with CAD.
The phenomenon that have been known to support this interconnection
but have been ignored are: that significant changes in gingival oxygen
utilization accompany inflammatory and healing states of gingival tissues
[6, 7]. Insufflation of oxygen into the periodontium appears to exert a
favourable therapeutic influence on periodontal disease [8]. There is a
genetically transmitted disorder of oxidative metabolism, acatalasemia in
which severe periodontal destruction results [9].
The measured endogenous respiration of gingiva might also be derived
Dental & Oral health Int. Journal, 2019
in part from oxygen utilization by gingival tissue PMNs, as was first
suggested by Glickman [6]. Now however, that the role of oxidative
metabolism of the PMN is rightfully assigned major importance for
its possible influence upon the health of periodontal tissues it seems
appropriate to us to bring together the scattering individual reports on
gingival oxidative metabolism.
Experimental Methods of Measurement
1. Serak’s Polarographic Method [10, 11]
The samples of human gingiva are obtained (extractions and other surgical
operations always carried out under local anesthesia and transported to the
laboratory on a cotton pad poised with cooled saline.
After removing the blood, the external part of gingival epithelium is
cut in the form of a slice of 0.2 to 0.3 mm in thickness (in contact with
cellophane membrane of the oxygen analysator by its keratinized side)
which is used to determine the oxygen consumption and the remaining
part is histologically examined by means of a common paraffin technique
and stained by hematoxyline eosine.
2. Warburg’s Manometric Method [6]
In the Warburg’s method, the tissue under investigation is dipped directly
into the medium, containing dissolved oxygen and is continually shaken
unlike the Serak’s method). This movement removes the concentration
gradient of oxygen at the surface of the slice under investigation, which
would virtually make any measurement impossible. It has been seen
that canine, bovine, and human gingiva had similar respiration rates.
Endogenous respirations studies in human skin revealed that the QO2 at
32°C ranged from 1.8 - 4.6 [12].
Ageing & O2 Consumption
Volpe et al [13] (1962) found that the endogenous respiration of gingival
sections declined with increasing age from a QO2 of 1.64 (0-20 years) to
1.26 (41- 60 years) (air. 37.5°C). However, such a difference might well
be within the range of technique variability.
O2 consumption in epithelial and subepithelial layers
Endogenous respiration was found to occur primarily within the epithelial
layer, and connective tissue elements were only slightly active. Thus,
Schrader et al reported that the QO2 of the separated epithelial cell layer of
human gingival ranged from 4.8-7.5 as compared to 1.47 observed in the
sub epithelial layer [14].
Oxygen Consumption / Endogenous Respiration
It is a value that has wide biochemical significance, according to which, it
is possible to judge the character and the intensity of metabolic processes
taking place in the tissue. The resulting values of oxygen consumption are
mostly expressed as the metabolic quotient QO2 = the amount of oxygen
in micrograms consumed by 1 milligram of dry weight of the tissue per
hour (µmoles Oz/ mg dry wt/hr) [10].
The normal oxygen consumption of gingiva has been measured as 1.6 +
0.37 [6].
Effects of inflammation and regeneration upon endogenous respiration:
Varying observations have been made by Glickman et al, noted values
increased progressively from a QO2 of 1.5 on Day 1 to 5.0 between the
12th to 20th days of healing, and returned to normal values in 20-30
days. Person [7] (1707) suggested that endogenous oxygen utilization
by gingiva increased during mild to moderate inflammatory changes, but
decreased as the inflammatory changes become more severe.
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Energy metabolism and various gene expressions are modulated by low
oxygen. Thus hypoxic responses are reported to be strongly related to
innate human responses [15].
Hypoxic cellular reaction and adaptation is crucial in periodontal innate
immune cells, which develop functional and survival responses regulated
by the oxygen sensor HIF (Hypoxic Inducible Factor). 16 Cellular pO2
levels influences the factors like trefoil factors, secreted molecules from
mucous epithelia which are involved in oral protection against tissue
damage and immune response [17, 18].
Experimental Periodontitis and O2 Consumption
As stated earlier, the Hb (Hemoglobin) concentration reflects the actual
gingival blood volume, and the Hb oxygen saturation depends on blood
tissue oxygen extraction. The result of the study showed that changes
in gingival oxygen metabolism appear to be characterized by a rapid
increase in gingival blood volume and oxygen consumption, therefore a
rapid decrease in Hb oxygen saturation during the first seven days [19].
Hence, it would be rationale to say that when the increase in blood supply
was not enough to meet oxygen demand, it leads to chronic inflammation.
The carotid body senses the drop in oxygen concentration in atmosphere
which then increases the rate and depth of breathing. HIF is a key cellular
transcription factor at the level of tissue and cells including the human
periodontium that mediate adaptive responses to low oxygen tension or
hypoxia [20]. Oxygen consumption is elevated and blood perfusion is
stimulated at sites of chronic inflammation but the actual microcirculation
could be compromised. It is attributed to increased oxygen consumption
by resident cells, infiltrated defense cells and also to diminished
oxygen availability due to endothelial damage and vasoconstricted
microcirculation [21].
The exact mechanism of hypoxia or HIF-1 α regulation in dendritic
cells and lymphocytes which has impact on the innate and adaptive
cellular immunity in periodontal tissues is yet to be elucidated. HIF-1α
has dual action on periodontal tissues, one being the defensive action
against periodontal pathogens while on other end it could also facilitate
periodontal tissue breakdown leading to progression of periodontitis.
HIF-1α has been found to be increased in both chronic and aggressive
form of periodontitis suggesting its role in pathogenesis of periodontal
diseases [22]. Hypoxia can be beneficial, while it can also be deleterious
to periodontal health [23].
Variability of O2 Metabolism in Different Situations
1. Vitamin Deficiencies and Periodontal Disease
• Scurvy: The effect of scurvy upon oxidative metabolism of
guinea-pig gingival metabolism was investigated by Honjo et al. who
stated that the enzymes of oxidative metabolism (Aconitase and NADP
isocitric dehydrogenase) activities decreased between 10-20% during the
development of scurvy [24]. cycle, mitochondrial terminal electron transport, and oxidative
• CoQ10 (Ubiquinone- a hydrogen carrier in the krebs cycle)
deficiencies: The effects of oral coenzyme Q10 (CoQ10) therapy in
periodontitis patients were evaluated by Wilkinson et al. [25]. These
investigators reported that patients who received 50 mg daily of CoQ10,
had reduced periodontal disease scores, decreased pocket depth, and
improved healing after gingivectomy when compared with patients who
received a daily placebo in a double blind experiment
2. Uncontrolled diabetes: It has been now shown that formation
of advanced glycation end-products (AGES) causes collagen
accumulation in blood vessels including periodontal capillary
basement membrane which decreases tissue perfusion and
oxygenation [26].
Dental & Oral health Int. Journal, 2019
3. Dilantin-induced gingival hyperplasia: It is associated with the
increase in hyperplasia, an increase in non-collagenous protein
(ground substances), and increased tissue oxidative metabolism
were observed to occur. Cytochrome oxidase activity was found to
be significantly greater in human dilantin hyperplastic gingiva than
in inflamed gingiva.
4. Smoking: Oxygen concentration in healthy gingiva in smokers is
less, but it increases in the inflamed tissue. Also, the neutrophils from
smokers show decreased chemotaxis, phagocytosis and oxidative
burst [27].
5. Stress: Manhold et al. tested the hypothesis that in long or continued
emotions, a constant constriction of the blood vessels would produce
a lack of oxygen and nutrient materials for the periodontal tissues.
They found a lower ability of the tissues of rats under stress to utilize
oxygen [28].
Oxygen Tension in Periodontal Pockets
Oxygen tension (pO2) of the tissue fluids is the balance between the
delivery of oxygen to the area by the circulatory system and the rate
of oxygen consumption occurring in the tissues. A spectrum of pO2 in
deep periodontal pockets seems to define the pocket microbiological
composition since anaerobic bacteria, that cause destructive periodontal
disease differ in regard to their oxygen sensitivity and tolerance to
the toxic effects of oxygen. It has been found that deeper contain less
oxygen than moderately deep sites [29]. Activation of HIF promotes
a metabolic switch to reduce oxygen consumption which occurs by
shifting energy metabolism from aerobic respiration to glycolysis [30].
Survival of anaerobic gram negative pathogens is enhanced by local
hypoxia in periodontitis. Increased HIF- 1 α protein is observed in
periodontal disease due to tissue hypoxia. It is detectable in affected
tissue biopsies using western blot and HIF-1 α immunostaining [31].
Clinical Applications
We all know the beneficial effects of hyperbaric oxygen therapy, in
conditions such as osteoradionecrosis etc., which has proved that oxygen
can accelerate healing where indicated. Manhold (1974) showed through
an experiment that some commercially available oxygenating agents
demonstrated shorter healing times when applied on inflamed gingiva
[32]. As previously mentioned, the therapeutic effects of Ubiquinone
Qio (topical and systemic), a hydrogen carrier in the Krebs cycle, which
increases the availability of oxygen has already been advocated in
literature and is now also available in gel form [33].
Conclusion
The following conclusions can be drawn
1. The hexose monophosphate shunt mechanism, citric acid
phosphorylation have been identified in gingiva.
2. The decline in O2 utilization and oxidative metabolism in severely
inflamed gingival tissue may be the result of tissue injury and
destruction brought about by chronic PMNs and other white cell
populations.
3. Vitamin deficiencies, diabetes etc. depress oxidative metabolism and
electron transport mechanisms in humans and animal gingiva.
4. Concrete evidence does exist to demonstrate interrelationships
between white cell population and gingival oxidative metabolism
currently.
5. It is suggested that quantitative studies of such interrelationships
should be initiated and that they will further increase our
understanding of gingival tissues in health and disease.
Conflict of Interest: No Conflicts of Interest
Volume 1 | Issue 2 | 3 of 4
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mechanism underlying accelerated periodontal disease associated
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