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Antioxidant Effect of Channa Micropeltes in Diabetic Wound of Oral Mucosa

Authors:
OPEN ACCESS International Journal of Pharmacology
ISSN 1811-7775
DOI: 10.3923/ijp.2019.137.143
Research Article
Antioxidant Effect of Channa Micropeltes in Diabetic Wound of
Oral Mucosa
1Maharani L. Apriasari, 2Yusfa Ainah, 2Eka Febrianty, 3Amy N. Carabelly
1Department of Oral Medicine, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia
2Faculty of Dentistry, University of Lambung Mangkurat, JI Veteran 128B, Banjarmasin, Indonesia
3Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia
Abstract
Background and Objective: Toman fish (
Channa micropeltes
) contains albumin which possesses antioxidant effect. People in south
Kalimantan, Indonesia, use toman fish as an alternative drug to accelerate diabetic wound healing process. In diabetic wound, there is
a reduction in superoxide dismutase (SOD) activity and an elevation in malondialdehyde (MDA) level which can lead to the occurrence
of delayed wound healing. The objective of this study was to prove the antioxidant effect of
Channa micropeltes
using SOD activity and
MDA level in diabetic wound of oral mucosa. Materials and Methods: This is an experimental study with post test-only control group
design. This study used 24 Wistar rats which divided into three treatment groups. The groups comprised of one group administered with
toman fish extract of 16 mL kgG1 rat BW per oral, one group as a positive control administered with Haruan fish extract of 13.54 mL kgG1
rat BW per oral and one group as a negative control given BR2 feed only. The SOD activity measurement was done through Misra and
Fridovich method using spectrophotometer in 480 nm wavelength. The MDA level measurement was done through Thiobarbituric Acid
(TBA) test from Buege and Aust method using spectrophotometry in 532 nm wavelength. Results: One-way ANOVA test of day 3 showed
no significant difference in SOD activity (p = 0.078) and MDA level (p = 0.094). Meanwhile, statistical result of day 7 showed significant
difference in SOD activity (p = 0.018) and MDA level (p = 0.011).
Post-hoc
LSD test showed significant difference between toman fish
extract of 16 mL kgG1 rat BW dosage and haruan fish extract of 13.54 mL kgG1 rat BW dosage and group given BR2 feed only.
Conclusion: It can be concluded that
Channa micropeltes
has an antioxidant effect which represented by the increase of SOD activities
and the decrease of MDA level in diabetic wound of oral mucosa.
Key words: Antioxidant effect,
Channa micropeltes
, diabetic wound, haruan fish, wound healing, toman fish
Received: September 15, 2018 Accepted: October 19, 2018 Published: December 15, 2018
Citation: Maharani L. Apriasari, Yusfa Ainah, Eka Febrianty, Amy N. Carabelly, 2019. Antioxidant effect of channa micropeltes in diabetic wound of oral
mucosa. Int. J. Pharmacol., 15: 137-143.
Corresponding Author: Maharani L. Apriasari, Department of Oral Medicine, Faculty of Dentistry, University of Lambung Mangkurat,
Jl Veteran 128B, Banjarmasin, Indonesia Tel: +6285850367843
Copyright: © 2019 Maharani L. Apriasari
et al
. This is an open access article distributed under the terms of the creative commons attribution License, which
permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Competing Interest: The authors have declared that no competing interest exists.
Data Availability: All relevant data are within the paper and its supporting information files.
Int. J. Pharmacol., 15 (1): 137-143, 2019
INTRODUCTION
People with Diabetes Mellitus tend to suffer chronic
wound which characterized by prolong healing process.
Complication of diabetes mellitus is comprised of the
occurrence of delayed wound healing as a result of
uncontrolled hyperglycemia. People of South Kalimantan,
Indonesia frequently consume toman fish (
Channa
micropeltes
) and Haruan fish (
Channa striata
) to accelerate
wound healing process1-3.
Empirically, patent drugs contain haruan extract have
been marketed in Indonesia. Haruan fish contains 4.53%
albumin which is equal to 13.54 mL kgG1 rat b.wt. Based on the
previous study, haruan fish is proven to contain albumin as an
antioxidant which can accelerate diabetic wound healing
process in 8 days4-7. Lately, Haruan fish is more difficult to
obtain so the presence of alternative resource is required. An
alternative resource used as the substitute of Haruan fish is
toman fish. Toman fish is known to be in the same family as
haruan fish and easy to cultivate because of its fast
regenerative property. The administration of toman fish
extract 16 mL kgG1 rat b.wt., dosage can accelerate wound
healing process8,9.
In diabetic wound healing of oral mucosa, there is an
occurrence of prolong inflammatory phase. Acute
inflammatory phase of diabetic wound healing process is
marked by an elevation of ROS production10. Excessive
number of ROS will inhibit diabetic wound healing process
as an effect of superoxide dismutase (SOD) activity
reduction11-13.
The SOD reduction can increase malondialdehyde (MDA)
level which can be overcame by the administration of toman
fish extract. Toman fish extract had been proven to contain
albumin. Albumin has abundance of sulfhydril (-SH) groups
which function as radical scavenger to bind ROS. The binding
of ROS will result in an increase of SOD activity which can
reduce ROS level in the body. This condition will be marked by
the reduction of MDA level in chronic inflammatory phase. In
diabetic wound, inflammatory phase then proceeds to
proliferative and remodeling phase until wound healing
process can be achieved4,14,15.
Omega-6 is a group of fatty acid derived from arachidonic
acid (AA) and chemical mediators such as prostaglandin and
lipoxin which playa role in inflammatory phase16. In the end of
inflammatory phase, wound healing process will proceed to
proliferative phase to achieve neovascular formation and re-
epithelialization. Furthermore, wound healing process will
continue to the maturation phase where synthesis of
extracellular matrix and closure of the wound will take place
in day 143,17.
Studies about
Channa micropeltes
extract for the
acceleration of diabetic wound healing is still limited. More
study about wound healing should be done. The main
objective of this research was to study the effect of
Channa
micropeltes
as an antioxidant by investigating SOD activities
and MDA levels in diabetic wound of oral mucosa.
MATERIALS AND METHODS
Research preparation: The study was an experimental
laboratory research with post-test only control group design.
Research procedure was approved by Ethical Clearance
Committee of Faculty of Dentistry, Universitas Lambung
Mangkurat, Banjarmasin, South Borneo, Indonesia with letter
No. 050/KEPKG-FKG ULM/EC/IX/2017. This study was done on
December, 2017 at Biochemistry Laboratory of Medical
Faculty, Universitas Lambung Mangkurat, Banjarmasin,
Kalimantan Selatan, Indonesia. Population of this study was
Wistar Rat. Inclusion criteria of the sample were male Wistar
rat, weigh 250-300 g, age 2-3 months and in a healthy
condition (active and have good appetite). Exclusion criteria
of the sample in this study were weight loss more than 10%
after adaptation at the laboratory, unhealthy condition
(in-active and has no appetite), abnormal rat (presence of
wound or disability) and death rat. Experimental animal was
divided into 3 groups comprised of negative control group
given BR2 feed only, treatment group administered with
toman fish extract of 16 mL kgG1 b.wt., dosage per oral and a
group administered with haruan fish extract of 13.54 mL kgG1
b.wt., dosage per oral. Each group consisted of 4 rats which
sacrificed in day 3 and 7.
Extract manufacturing: Toman fish or haruan fish used in this
study had total weight of 11 kg. Part of the fish used was the
flesh of toman fish and haruan fish. Toman fish and haruan
fish used was firstly cleaned from the heads, guts and scales.
The flesh was then weighed of 9.84 kg and steamed in close
pan for ±30 min until 750 mL of yellowish pale liquid was
obtained and separated. The flesh of toman fish and haruan
fish then put into hydraulic press to proceed. Toman fish and
haruan fish extract were put into reaction tube for 7.5 mL
separately and centrifuged for 15 min with 6000 rpm speed.
The centrifugation resulted in 750 mL liquid, comprised of
50 mL extract which then stored in dark glass bottle covered
by aluminum foil and clean pack18.
Diabetes mellitus induction in Wistar rat: The model of oral
mucosa diabetic wound was obtained by injecting
streptozotocin (STZ) in male W istar rat w ith 35 mg kg G1
138
Int. J. Pharmacol., 15 (1): 137-143, 2019
2.5
2.0
1.5
1.0
0.5
0.0
SOD enzyme (unit mL )
G
1
1.909
1.184
0.906
0.356
0.122
0.332
Day 3 Day 7
Feed only
Toman fis h
Haruan fish extract
MDA level (mmol L )
G
1
177.750
176.500
174.750
179.250
177.000
178.000
Day 3 Day 7
Feed only
Toman fis h
Haruan fish extr act
180
179
178
177
176
175
174
173
172
dosage. Rat was given BR2 feed twice a day and then
examined 7 days later. Glucose level in rats was measured by
glucometers which done before and after the administration
of STZ. Rat was diagnosed with diabetes when blood glucose
level was over 126 mg dLG1. The condition of Wistar rat which
suffered with diabetes was limped, in-active and show no
appetite18.
Model of diabetic wound in oral mucosa: Experimental
animal used was male Wistar rat which was adapted
previously for a week inside the cage at laboratory. Wistar rat
right buccal mucosa was taken and measured for wound
making. Operators hands were firstly washed and then
covered using sterile gloves. The procedure was continued
with sedation using 0.75 mL diethyl ether for 5-10 min until
the rat was put to sleep. Incision wound was made at 10
mm length and 1 mm depth on right buccal mucosa of
Wistar rat using scalpel and disposable blade number 15,
blood was cleaned by sterile aquadest.
Rats from each group were sacrificed after sedated by
inhalation method using diethyl ether on day 3 and 7.
Sacrificed rat was then biopsied by taking the tissue of oral
mucosa around erythematous area with 3 mm length, 3 mm
width and 3 mm in-depth. Biopsied tissue was weighed for
0.2 g and crushed with cold mortar after added with 1 mL
physiologic NaCl. Homogenate was moved to microtube and
centrifuged with 8000 rpm speed for 20 min. The SOD activity
and MDA level examination was done on 500 mL supernatan
using spectrophotometer on day 3 and 7. The SOD activity
measurement was done through Misra and Fridovich method
using spectrophotometer at 480 nm wavelength. The MDA
level measurement was done through Thiobarbituric Acid
(TBA) of Buege and Aust method using spectrophotometer at
532 nm wavelength. Based on the measurement of SOD
activity and MDA level19. Normality test was done using
Shapiro-Wilk test and homogeneity test using Levene's
test.
Statistical analysis: Data is statistically analyzed by One-Way
ANOVA with significance level p<0.05 and then analyzed using
post-hoc
LSD test.
RESULTS
The statistical result showed that data was normally
distributed and homogenous with p>0.05 on day 3. The
data then proceeded to parametric analysis using
one-way ANOVA where p-value = 0.078 (p>0.05) for
SOD activity and p -value = 0.094 (p >0.05) f or MDA level
on day 3. This showed that there was no significant
difference among the treatment groups.
Statistical analysis of SOD activity and MDA level on day
7 showed that data was normally distributed and
homogenous with p>0.05. The analysis was continued with
parametric test using one-way ANOVA. One-way ANOVA test
for SOD activity obtained p = 0.018 (p<0.05) and MDA level
obtained p = 0.011 (p<0.05). This statistical analysis showed
that there was a significant difference among the treatment
groups. The data then analyzed using
post-hoc
LSD test.
Post-hoc
LSD analysis result on SOD activity and MDA
level showed significant difference on day 7 between toman
fish extract of 16 mL kgG1 rat b.wt., dosage group and haruan
fish extract of 13.54 mL kgG1 rat b.wt., dosage group. There
was a significant difference between toman fish
extract of 16 mL kgG1 rat b.wt., dosage group and BR2 feed-
only group.
The elevation of SOD activity on buccal mucosa wound of
Wistar rat on group administered with toman fish extract,
haruan fish extract and feed only on day 3 and 7. Different
SOD activity on rat buccal mucosa wound at each group on
day 3 and 7 can be seen in Fig. 1. The highest SOD activity
elevation among the three groups respectively are toman fish
extract, haruan fish extract and feed-only group in sequence.
A decrease of MDA level on rat buccal mucosa wound
which administered with toman fish, haruan fish and
feed-only on day 3 and 7. Results in Fig. 2 depicted the
Fig. 1: Mean value of SOD activity (enzyme unit mLG1) on
buccal mucosa wound of Wistar-strain rat with diabetes
mellitus on day 3 and 7
Fig. 2: Mean value diagram of on buccal mucosa wound of
Wistar rat with diabetes mellitus on day 3 and 7
139
Int. J. Pharmacol., 15 (1): 137-143, 2019
different MDA level on buccal mucosa wound of wistar rat
with diabetes mellitus in each group on day 3 and 7. The
lowest MDA level among the three group respectively were
toman fish extract, haruan fish extract and BR2 feed-only
group.
DISCUSSION
The result of this study showed an increase of SOD
antioxidant activity and a decrease of MDA level on day 3
and 7. Toman fish extract administration of 16 mL kgG1 rat BW
dosage per oral showed satisfactory effect compared to
haruan fish extract of 13.54 mL kgG1 b.wt., dosage and BR2-
only to increase SOD antioxidant activity and decrease MDA
level on buccal mucosal wound in rat with diabetes mellitus.
Diabetes mellitus is one of chronic disease caused by
metabolic disorder with hyperglycemic condition that induce
an increase of advanced glycation end products (AGEs). This
is caused by a high blood glucose level on hyperglycemic
condition and induces glycation reaction (non-enzymatic
reaction between glucose and protein). This reaction can form
Schiff base which can produce amadory products. Amadory
products can form a very toxic protein called advanced
glycation end product (AGEs). This causes a prolong wound
healing process in diabetes mellitus patients20.
Advanced glycation end products (AGEs) are produced
from Maillard reaction which is signed by the presence of
alkylated amino acid, fluorescence residues and intra or
intermolecular cross-linkage. Interaction between AGE and
receptor advanced glycation end product (RAGE) will increase
the signaling of nicotinamide adenine dinucleotide phosphate
(NADPH) oxidase which produces superoxide anion (·O2). This
process will contribute to the increase of Reactive Oxygen
Species (ROS) production21,22.
Reactive Oxygen Species (ROS) occurs by the presence of
free radical production and antioxidant capacity
imbalance19,21. The reduction of antioxidant numbers are
mostly caused by impairment in the activation of nuclear
factor-erythroid-2 related factor 2 (Nrf2). Nrf2 is a transcription
factor which regulates genes for the coding of antioxidants
and detoxification enzymes. In physiological condition,
oxidative stress will trigger the up regulation of endogenous
antioxidants and cytoprotective proteins to prevent or limit
tissue destruction. This process is mediated by Nrf2 activation
which will influence the rate of various antioxidant genes and
detoxification enzyme transcription. The interaction of
oxidative stress and inflammation shows inseparable relation.
Oxidative stress can induce inflammatory stress through NF-kb
activation and inflammation can release ROS vice versa23,24.
An increase in ROS production will result in tissue
destruction and dysfunction by attacking, denaturating and
modifying molecule structure and function. This process also
involves the activation of transcription factor which is sensitive
to redox and signal transduction pathway. This condition will
increase the occurrence of necrosis, apoptosis, inflammation
and fibrosis. Redox systems including antioxidants and
detoxification enzymes will protect tissue from destruction
caused by ROS. Nrf2 also plays another role in inflammatory
process which inhibits the transcription factor of NF-kB to
induce the reduction of inflammatory process. Nrf2
dysregulation will induce the reduction of NF-kB transcription
factor and increase several genes to encode the expression of
inflammatory mediators25-27.
Inflammation in diabetes mellitus occurs when there is an
increase of ROS production. This is caused by the reduction of
superoxide dismutase (SOD) activity which is marked by the
increase of MDA level as peroksidasi lipid end product. High
MDA level is an evidence of low antioxidant status in the body
such as the quantity of SOD. However, this state can be
overcame by the administration of exogenous antioxidants,
one of them is albumin, which can be found in toman fish
extract28-30.
The SOD activity and MDA level statistical analysis on
day 3 of diabetic Wistar rat buccal mucosa wound in each
treatment groups of BR2, toman fish extract and haruan fish
extract shows no significant difference. It is caused by a short
administration time of toman fish extract which will result in
less number of exogenous antioxidant administered. Wistar rat
group on day 3 obtained less number of exogenous
antioxidants compared to day 7. This shows that the lower the
antioxidant concentration given, the less the antioxidant
activity obtained to neutralize excessive amount of ROS in
acute inflammatory phase of diabetic wound healing process.
The statistical analysis result on day 3 is not significantly
different.
Buccal mucosa wound of Wistar rat with diabetes mellitus
on day 7 which administered with toman fish extract and
haruan fish extract shows significant difference. This can be
seen from the result of SOD activity and MDA level statistical
analysis result. There is a significant difference caused by the
presence of higher albumin content as an antioxidant in
treatment group on day 7 compared to day 3.
Albumin is a secondary antioxidant which can bind metal
ion in ROS formation process. It can act as an oxygen binder
and also as hydroperoxide analyst to radical compound and
free radical obtained from oxidative process. Albumin is an
extracellular antioxidant comprised of abundance sulphydryl
(-SH) groups which function as free radical binder. (-SH) group
140
Int. J. Pharmacol., 15 (1): 137-143, 2019
in albumin can react with ROS. Albumin helps SOD to prevent
ROS and lipid peroxide formation. Albumin can also react with
aldehyde resulted from peroxide lipid and inhibit lipid
peroxidation process. Albumin which reacts with
polyunsaturated fatty acid (PUFAs) can act as a defense
mechanism from radical destruction31-33.
Polyunsaturated fatty acids is fatty acids which contain
more than one double bond. Polyunsaturated fatty acids can
produce a product called MDA. Malondialdehyde is one of
aldehyde compound which is formed by peroxide lipid
process. This shows that excessive MDA level can be
constrained by albumin as one of exogenous antioxidant
which can help the activity of endogenous antioxidant such as
SOD32,33.
Albumin as exogenous antioxidant can increase SOD
through the signaling of nuclear factor erythroid2-related
(Nrf2) which is an important cytoprotective transcription
factor34. Nrf2 will be activated by the presence of oxidants,
electrophiles or endoplasmic reticulum stress. Nrf2 is
comprised of 6 domains: Neh1 contains bZIP structure which
is needed for binding DNA and forming dimer, Neh2 site can
interact with Keap1, Neh 3,4,5 which intervenes Nrf2
transactivation by binding with CREB binding protein (CBP)
and Neh6 domain which functions in the negative regulation.
In inactive condition, Nrf2 is located in cytoplasm and
inactively bind with Kelch-like ECH associated protein 1 (Keap)
repressor molecule to form Nrf2-Keap1 complex27,35.
Keap1 is comprised of several cysteine residues which act
as a sensor on intracellular redox status. Nrf2 will be rapidly
degraded by proteasome ubiquitine pathway. Signal from ROS
and electrophile will cause Nrf2 dissociation from Keap1 and
then Nrf2 will be translocated to nucleus. In nucleus, NRf2
binds with regulatory sequence called antioxidant response
element or electrophile response elements (ARE/EpRE) located
in promotor region of gene which encodes antioxidants and
detoxification enzymes36,37.
This process is mediated by heterodimerization of Nrf2
with other transcription factor, such as small Maf which
presence in the nucleus. This process then increase the
transcription of various related antioxidants, detoxification
enzymes and proteins such as catalase, superoxide dismutase,
NADPH quinone oxidoreductase, heme oxygenase-1,
glutathione S-transferase, glutathione peroxidase, thioredoxin,
which detoxificate various damaging xenobiotic38.
Nrf2 activation induces the increase of endogenous
antioxidant enzyme, SOD, by binding the antioxidant response
element (ARE)39. The increase of SOD activity can neutralize
excessive number of ROS in the form of superoxide anion
through superoxide dismutase enzyme catalytic reaction.
Superoxide dismutase catalytic enzyme reaction will change
superoxide anion to form hydrogen peroxide (H2O2) through
oxidation and reduction reaction of metal cofactor which
presence in SOD40. Hydrogen peroxide is then catalyzed into
water (H2O) and air (O2). Hydrogen peroxide in lower rate can
modulate various pathways for wound healing so SOD will
increase. The elevation of SOD activity can suppress excessive
quantity of ROS which also followed by the decrease of MDA
level. This can accelerate wound healing process in diabetes
mellitus patients11,41.
CONCLUSION
Based on this research, there was a significant difference
in the administration of toman fish extract of 16 mL kgG1 b.wt.,
dosage, haruan fish extract of 13.54 mL kgG1 b.wt., dosage and
rat given BR2 feed only in increasing SOD activity and
decreasing MDA level on buccal mucosal wound of Wistar-
strain rat with diabetes mellitus on day 3 and 7. It can be
concluded that
Channa micropeltes
has an antioxidant effect
by increasing SOD activities and decreasing MDA levels in
diabetic wound of oral mucosa. This research can be used as
an alternative medicine to accelerate diabetic wound healing,
both wounds that occur on the oral mucosa or skin. It can be
used as a basis for the next research to find the new drug.
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... Anti-diabetic of Extrac t M.oleifera and Ifalmin (C.micropeltes) (Nilamsari, et al.) 38 Ifalmin to reduce inflammation in diabetes conditions [10]. ...
... Meanwhile, Ifalmin has been reported contain high level of Albumin. Albumin from ifalmin can act as antioxidant soit can inhibit formation of ROS [10].Albumin has the potential to reduce the number of macrophages by increasing Th2 cells by secreting IL-10 and TGF-β anti-inflammatory cytokines [26]. Toman fish (Channa micropeltes) also contain omega 6, which has derivatives of Arachidonic Acid (AA), which will be converted into lipoxins and have the potential to reduce the risk of inflammation due to diabetes [27]. ...
Article
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In Indonesia, the prevalence of diabetes mellitus hits 6.2%, making Indonesia one of the top ten diabetes mellitus countries. Efforts to prevent and treat people with diabetes in Indonesia are required to minimize that as well. One is through treatment with local herbal products such as Moringa oleifera (MO) and Toman fish extract (Channa micropeltes), called Ifalmin. The aim of this research is to investigate the potential role of a combination of Extract Moringa oleifera and Ifalmin to reduce inflammation in diabetes conditions. Diabetic mice were done by Streptozotocin (STZ) induction with a single-dose 145 mg.kg-1.Then, diabetic mice were given an oral treatment of combination MO extract and Ifalmin for 14 days. In this experiment combinations of MO extract and Ifalmin are divide into 3 dose, There are: dose 1 (800 mg.kg-1 : 800 mg.kg-1), dose 2 (650 mg.kg-1 : 650 mg.kg-1), and dose 3 (800 mg.kg-1 : 650 mg.kg-1). Immune cells originate from the spleen are stained by immunofluorescence antibodies and analyzed by flow cytometry with BD Cellquest ProTM software. The results showed an increase of expression pro-inflammatory cytokines IL-1β and IL-6 in diabetic mice compared to normal control. Only dose 1 and dose 2 has shown the capability to reduce the expression of IL-1β in diabetic mice. But, the combination of MO and Ifalmin has an antagonist effect on the expression of IL-6. The inhibitory mechanism can be assumed by the action of antioxidant compounds (Flavonoids and Alkaloids) in MO and Albumin compound in Ifalmin. Those combination act as exogenous antioxidant that help endogenous inside the body. A combination of MO extract and Ifalmin with a certain dosage was able to decrease proinflammatory cytokines IL-1β on the cells involved in innate immunity.
... Albumin is known able to activate the signaling of nuclear factor erythroid2related (Nrf2) for antioxidant and other enzymes, including heme oxygenase-1 (HO-1). 45 Activation of HO-1 eventually promotes the anti-inflammatory activity by inducing the expression of anti-inflammatory cytokines IL-10 and IL-4. [46][47] Albumin possibly suppressed the production of TGF-β in type 1 diabetic mice through ROS levels reduction. ...
... Albumin has abundant sulphydryl (-SH) groups which can bind with free radical so that it can decrease the levels of ROS. 45 We also compared the effect of MC in anti-inflammatory cytokines with a standard drug, metformin. Metformin exerted its anti-inflammatory effect by up-regulating the expression of anti-inflammatory cytokines IL-10 and IL-4. ...
... DM is also notable as an inflammatory disease in which the production of reactive oxygen species (ROS) is intensified. 3,4 An increase of ROS in the inflammatory stage of the diabetic healing process will lead to inevitable results such as a prolonged healing process in the oral mucosa. 4,5 Pathological symptoms in the soft tissues, including; a reduction in salivary flow, xerostomia and taste disorders may often be identified in patients suffering from DM. Mucosal lesions resulting from fungal infection (oral candidiasis and angular cheilitis), bacterial infection (gingivitis and periodontitis), viral infection (herpes labialis and herpes zoster) and other lesions (oral lichen planus, lichenoid reaction, recurrent aphthous stomatitis) can also frequently be observed. ...
... 3,4 An increase of ROS in the inflammatory stage of the diabetic healing process will lead to inevitable results such as a prolonged healing process in the oral mucosa. 4,5 Pathological symptoms in the soft tissues, including; a reduction in salivary flow, xerostomia and taste disorders may often be identified in patients suffering from DM. Mucosal lesions resulting from fungal infection (oral candidiasis and angular cheilitis), bacterial infection (gingivitis and periodontitis), viral infection (herpes labialis and herpes zoster) and other lesions (oral lichen planus, lichenoid reaction, recurrent aphthous stomatitis) can also frequently be observed. 6,7 This case report seeks to elaborate the management of herpes labialis, oral thrush and angular cheilitis as oral manifestations in diabetic patients. ...
Article
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Background: As reported in several studies, prolonged or uncontrolled cases of diabetes mellitus (DM) may induce a more extreme inflammatory response. Mucosal lesions can be observed in patients who present this systemic condition. Purpose: The purpose of this study was to elaborate the management of herpes labialis, oral thrush and angular cheilitis as oral manifestations of diabetes. Case: A 49-year-old male complained of having experienced painful lip ulceration for the preceding seven days. The anamnesis of the patient revealed that, prior to lip ulceration, he had experienced high fever and malaise in addition to frequent urination at night and a tingling sensation in the toes and fingertips on waking. Case management: The patient was referred to undergo blood count, fasting blood glucose and oral glucose tolerance tests. The blood test result confirmed the patient to be suffering from DM and anemia. The immunocompromised condition of the patient prompted the occurrence of herpes labialis, oral thrush and angular cheilitis. Conclusion: Multidisciplinary treatment for herpes labialis resulting in oral candidiasis in DM patients is indispensable. Concurrent infection with HSV and candidiasis necessitates a more prolonged healing process. Consequently, it is a essential to treat the hyperglycemia which induces an immunocompromised state in diabetic patients.
... 6 Oral CM at a dose of 16 mL/ kg BW has been shown to have antioxidant properties that can increase SOD and reduce MDA in diabetic wounds. 7 The oral administration of 16 mL/kg BW dose has also been proven to increase the amount of neovascular on day 4 and reduce the amount of neovascular on days 8 and 14 in diabetic wounds. 8 The use of CM extract at a dose of 16 mL/kg BW orally is proven to general optimal wound closure and wound contraction clinically in Wistar rats as diabetic model on day 14. 9 However, the histopathological description of wound healing is yet to be known. ...
Article
Full-text available
Background: Diabetes mellitus (DM) is characterized by persistent hyperglycemia. The symptoms of DM is delayed wound healing. Delayed wound healing in diabetes will increase the risk of wound complications that will hinder the healing process, and lead to complications such as fibrosis and necrosis. The use of Channa Micropeltes (CM) extract at a dose of 16 mL/kg BW orally is proven to general optimal wound closure and wound contraction clinically in Wistar rats as diabetic model on day 14.However, the histopathological description of wound healing is yet to be known. Objective: To analyze the effect of 16 mL/kg BW dose of CM extract on histopathological changes of wound healing granulation tissue, fibrosis and necrosis in diabetic Wistar rats on day 14. Materials and Methods: This study was a true experimental design with a post-test only control group design. The samples were divided into two groups, namely the diabetic model group given CM extract at 16 mL/kg BW dose for 14 days, and the diabetic model group given BR2 feed only for 14 days. Results: The results of Mann-Whitney U test showed p = 0.003 for granulation tissue, p = 0.411 for fibrosis and p = 1 for necrosis, with the level of significance was p<0.05. Conclusion: The CM extract at 16 mL/kg BW dose affects the histopathological description of granulation tissue which presents a better result than those in the control group but did not affect the features of fibrosis and necrosis in diabetic Wistar rats on day 14. Keywords: Channa Micropeltes, Diabetic wound, Fibrosis, Granulation tissue, Necrosis.
... Albumin in Ifalmin® is known to activate Nrf2 signaling for gene expression of endogenous antioxidant enzymes, including superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione S-transferase, and glutathione peroxidase [34]. Some studies demonstrated that antioxidant enzymes were decreased in DM conditions [35,36]. ...
Article
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It has been known that the immunoglobulin levels were altered in diabetes mellitus (DM) conditions. This study aimed to evaluate the levels of immunoglobulins in DM mice after the administration of Moringa oleifera-Ifalmin® formulation (MI). Streptozotocin, at a dose of 145 mg.kg-1, was injected intraperitoneally to experimental mice to obtain diabetic mice. The groups were divided into normal mice, diabetic mice without treatment, diabetic mice with metformin treatment (307.5 mg.kg-1 BW), and diabetic mice with MI treatment at dose 1 (M:I= 800 mg.kg-1 BW: 800 mg.kg-1 BW), dose 2 (M:I= 615 mg.kg-1 BW: 615 mg.kg-1 BW), and dose 3 (M:I= 800 mg.kg-1 BW: 615 mg.kg-1 BW). Mice were orally treated by MI for 14 days. Subsequently, the levels of immunoglobulin IgM and IgG were evaluated using flow cytometry analysis. IgM and IgG levels were significantly lower in the DM group than the normal group. These results indicated that DM altered immunoglobulin levels. MI treatment for 14 days significantly increased the number of IgM and IgG at the level equivalent to the normal group and significantly different as compared to the DM group. Based on the results, MI can be used as an immunomodulatory agent in humoral immunity through the precise regulation of IgM and IgG.
... The rat were iagnosed with DM when the blood glucose level reached ≥ 126 mg dL -1 . 27 Wounding of rat's back began by adapting the rat at laboratory environment for 1 week. The hair on the back of rat were shaved with 3 cm diameter and cleansed with 70% ethanol. ...
Article
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Toman fish contains albumin and omega-6 fatty acid that are instrumental in the healing process of diabetes mellitus (DM) wound. People with DM usually have a prolonged wound healing process. Albumin controls the osmotic pressure, the development of granulation tissue, gives the energy to re-epithelialisation process and collagen base material. Omega-6 fatty acid interrupts phagocytosis induced by neutrophil cells. It increases the action of machropage cell, so that Toman fish can be used as an alternative in accelerating the DM wound healing process. The purpose of this research is to prove the effect of Toman fish extract at 16 mL/ KgBW rat dosage per oral on wound length and contraction on the back of wistar rat (Rattus novergiucs) with DM for 14 days. It was the experimental with a posttest only with control group design used 12 wistar rat that were divided into 3 groups; the group of Toman fish extract with dose 16 mL/ Kg BW rat, positive control group using Haruan extract with dose 13,54 mL/ Kg BW rat and negative control group using Comfeed BR2 feed. One-way ANOVA test result for wound length and contraction (p= 0,000). The result Post-hoc Least Significant Difference test for wound length and contraction shows that there are significant differences between the group of Toman fish extract and Haruan fish extract (p= 0,000). There is also significant difference between the group of Toman fish extract and Comfeed BR2 feed (p= 0,000). There is no significant difference between the group of Haruan fish extract and Comfeed BR2 feed (p= 0,930). The research concluded that Toman fish extract at 16 mL/ Kg BW rat dosage affects the length and contraction of diabetic mellitus wound. Keywords: Channa micropeltes, clinical analysis, diabetes mellitus, wound
Article
Introduction: Wound healing is an integrated response to tissue injury. A hyperglycemic state can lead to delayed wound healing process. Snakehead fish ( Channa striata ) is native freshwater fish of South East Asia that contains high protein, albumin, and several micronutrients. The aim of this study is to evaluate the efficacy of snakehead fish extract on acute wound healing process in streptozotocin-induced hyperglycemic rats. Methods: This study was an experimental trial on the hyperglycemic animal model. Thirty male Wistar streptozotocin-induced rats were divided into two groups which were then given snakehead fish extract (Pujimin Plus®) 81mg a day for 10 days after wound infliction in intervention group and carboxymethyl cellulose sodium (Na-CMC) in control group. On day 0, day 3, and day 10 after wound infliction, the histological changes (number of neutrophil and fibroblast, and vascular changes of the wounded tissues) of each group were analyzed. Assessments were also made on erythema and crust formation by the visual scores. Results: Our study showed a significant increase in the number of fibroblasts on day 3 in the snakehead fish extract group compared to control group (40.33 ± 10.13 vs. 24.60 ± 10.25, p =0.04). There were no significant differences in vasculature and neutrophil numbers. The results also showed snakehead fish extract could decrease mean erythema visual score on day 3 (3.24 ± 0.25 vs. 3.64 ± 0.35) and decreased crust formation on day 5 (3.36 ± 0.75 vs 3.44 ± 0.83). Conclusions: Snakehead fish extract has potential effect to accelerate the wound healing process by increasing fibroblast, decreasing erythema, and decreasing crust formation in streptozotocin-induced hyperglycemic rats.
Article
This study aimed to evaluate the effect of Moringa-Albumin (MA) combination on pro-inflammatory cytokine expressions, especially IFN-γ and TNF-α, in a diabetic mouse model. Streptozotocin with a 145 mg/kg BW dose was used to induce diabetes condition in BALB/c mice. Mice with positive DM (blood glucose levels ≥ 200 mg/dL) were orally administered with MA for 14 days at dose 1, dose 2, and dose 3. On day 15th, spleen cells were isolated to analyze IFN-γ and TNF-α expressions by flow cytometry. The data were statistically analyzed with one-way ANOVA (ρ≤ 0.05) and Tukey test using SPSS version 16 for Windows. The results showed that the MA combination had anti-inflammatory activity in inhibiting IFN-γ and TNF-α. Furthermore, dose 1 affected to decrease in the IFN-γ expression while dose 3 decreased the expression of TNF-α. Thus, it can be concluded that the MA combination has a role in inhibiting IFN-γ and TNF-α in a dosage-dependent manner. Based on the results, we assumed that MA might be one of the biological materials with efficacy to treat DM patients.
Book
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Channa is a genus of freshwater fishes usually known as snakehead fishes. In several regions in Indonesia and Malaysia it has long been known and used as functional food to accelerate wound healing, especially for newly circumcised boys and women after giving birth. It is believed that consumption of Channa fishes will increase stamina, reduce pain, and accelerate wound healing. The delicious taste of the fish also expected to increase appetite so that it will add vitality. Some recent researches conducted in the past ten years revealed that Channa fishes contains high protein, especially albumin. It also contains Zinc in quite high amounts Both albumin and Zn are compounds needed in the wound healing process. This book described the biology of Channa fishes found in Indonesia, as well as their biological and medicinal potential. It also described the nutritional content, bioactive compounds and biological activities of Channa fishes reported from many researches. The last chapter presented in more details the results of research carried out specifically to reveal the effectiveness of Channa lucius supplementation in enhance wound healing, either in diabetic wounds or non-diabetic wounds.
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