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Egypt. J. Comp. Path &Clinic Path. Vol. 28 No.1, 2015 ; 103- 116 ISSN 1110-7537
103
Clinico-pathological Studies on The Regulatory Effect
of Cinnamon on Metabolic Disorders in High
Fructose-Fed Mice
Walaa M.S. Ahmeda, Nermeen A. Helmy
b and Taghreed M.Nabil
c
a. Department of Clinical pathology, faculty of veterinary medicine, Beni-suef university.
b. Department of Physiology, faculty of veterinary medicine, Beni-Suef university.
c. Department of Cytology and Histology, faculty of veterinary medicine, Beni-Suef university.
ABSTRACT— In the current study we investigate the possible effect of cinnamon against
some metabolic changes induced by high fructose intake in mice. For this purpose, eighty mice
were divided into four groups, the first one kept as control. In the second group, mice were given
high fructose (20%) in water per day for 8 weeks. In the third and fourth groups, mice were
given fructose as in the second group and orally administrated cinnamon daily for 8 weeks in a
dose rate of 150 and 300 mg/kg b.w, respectively. Body weights were recorded weekly and oral
glucose tolerance test was carried out at the end of experiment. Hepatic enzymes (ALT, AST and
ALP), glucose, lipid profile (total cholesterol, triglyceride, HDL-c and LDL-c), TNF-α levels
were estimated. Mice liver of were weighted and its antioxidant enzymes (GSH, CAT) content
and lipid peroxidation (MDA) level were measured. Results indicate no change in hepatic
enzymes in fructose-fed mice. Co-administration of cinnamon with fructose resulted in decrease
the elevated glucose and TNF-α values. Moreover, cinnamon improve the disturbed lipid profile.
The depletion of antioxidant enzymes and increased MDA activity by fructose intake were
ameliorated in cinnamon treated mice. Examination of liver by light and electron microscopy
revealed fatty change, cloudy swelling, inflammatory cells infiltration in fructose-fed mice which
were markedly improved by cinnamon treatment at dose of 150 mg/kg. In conclusion, co-
administration of cinnamon at dose of 150 mg/kg was more effective than the higher dose and
regulate the disturbed metabolic changes that induced by high fructose intake in mice.
Key words: Cinnamon; High fructose- diet; Histopathology; Metabolic disorders; Mice.
—————————— ——————————
INTRODUCTION
Nutritional overfeeding of fat and or
refined carbohydrates is a contributing factor
to the development of a complex pattern of
disorders that include insulin resistance,
dyslipidemia, diabetes, obesity,
atherosclerosis, and cardiovascular disease
(Marissal-Arvy et al. 2014). Glucose and
lipids are key components in energetic
metabolism. Excess energy intake is
responsible for an inappropriate processing of
the glucose and lipid. This extreme energy
will stored in adipocytes which produce high
levels of adipokines and inflammatory
cytokines that affect the vascular system
(Galic et al. 2010). Some of these cytokines
(tumor necrosis factor interleukin-1band and
interleukin-6) could be involved in initiating
of insulin resistance (Bastard et al. 2006).
To gain insights into the association between
diets and these diseases and develop effective
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
104
therapy, animal models have been developed
that typically rely on genetic manipulation,
toxic injury [e.g., methionine- and choline-
deficient diet], or dietary extremes (e.g.,
abnormally high-fat or high-fructose diets)
(Anstee and Goldin, 2006).The metabolism
of fructose is done by the liver. High fructose
intake develop metabolic consequences such
as hyperinsulinemia, insulin resistance,
dyslipidemia, hyperuricemia, inflammation,
oxidative stress, and disrupted status of
adiponectin, leptin and tumor necrosis factor-
a (Kitagawa et al. 2012). Most of
conventional drug treatment of insulin
resistance have undesirable side effects such
as weight gain, fluid retention, and an
increased risk of myocardial infarctions.
Whilst, medicinal plants are expected to have
a similar degree of efficacy without the
troublesome side effects associated with
pharmacological treatments (Eddouks et al.
2015).
Dietary botanical supplements are a
valuable source of therapeutics for preventing
epidemic diseases such as obesity,
cardiovascular disease and diabetes (Cheng
et al. 2012). Cinnamon, one of the widely
used flavoring agent and medicinal plant
belonging to the family Lauraceae, possess a
significant anti-bacterial, anti-fungal, anti-
inflammatory, antioxidant and anti-diabetic
properties (El Hasnaoui et al. 2015).
In the present study, we have studied
the impact of high-fructose consumption and
elucidated the influence of cinnamon on the
metabolic alterations induced by high-
fructose intake in mice.
MATERIALS AND METHODS Fructose was obtained from (Sigma
company, USA), and was prepared in 20 %
solution.
Cinnamon bark (Cinnamomum zeylanicum)
was purchased from the local market.
Glucose, Alanine aminotransferase
enzyme (ALT), aspartate aminotransferase
enzyme (AST), alkaline phosphatase enzyme
(ALP) reagent kits were obtained from
Biodiagnositic Company, Egypt. Total
cholesterol (TC), triglyceride (TG) and high-
density lipoprotein (HDL) was performed
using reagent kits from Spin react (Spain).
reduced glutathione (GSH), Catalase (CAT)
and malondialdehyde (MDA) were
estimated using commercial kits (Bio-
diagnostic for Research Kits, Egypt). All
the chemicals were of analytical grade
and were procured from local commercial
companies.
2.1. Study design
A total of 80 BALB/c mice were
purchased from Research Institute of
Ophthalmology, Financial management
(Giza, Egypt). The animals were handled and
cared in accordance with the guidelines of
Beni-Suef University for animal use. After 1
week of acclimatization, mice were randomly
divided into 4 groups (n=20/group). One
group was kept as negative control; a second
group was given 20 % fructose in water; a
third group was given 20 % of fructose along
with cinnamon in a dose of 150 mg/kg b.w; a
fourth group was given 20% fructose along
with cinnamon in a dose of 300 mg/ kg b.w.
The Cinnamon bark was finely
powdered in a mechanical mixer, weighted
then dissolved in water and kept in a water
bath at 60°C for two hours and filtered.
Cinnamon was administered orally to mice
once a day for two months. Body weight of
mice was determined weekly till the end of
the experiment.
Oral Glucose tolerance test (OGTT) The oral glucose tolerance test was
performed in the last day of the experiment
according to Yadav et al. (2007).
2.2. Sample collection
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
105
From all groups, blood samples were
collected from the orbital venous plexus,
allowed to clot for 20 minutes and then were
centrifuged at 3000 rpm for 10 minutes.
Serum was separated and stored at -20 ºc till
analysis. The mice were euthanized by
cervical dislocation and liver was dissected
and weighted in order to calculate the
organ/body weight ratios for each mice.
Then, part of liver tissue was used for
histopathological studies. Another part was
prepared for estimation of GSH, CAT and
MDA according to Ahmed et al. (2014).
2.3. Laboratory analyses.
2.3.1. Serum hepatic enzymes. The activities of ALT and AST
enzymes were estimated with colorimetric
method (Reitman and Franel, 1975).
ALP activity was measured according to
Belfield and Goldberg (1971).
2.3.2. Blood glucose estimation Glucose level was estimated
according to Trinder (1969).
2.3.3 Lipid profile was determined by
measuring the content of total cholesterol,
triglycerides, HDL-c and LDL-c
concentrations with a standard colorimetric
method using reagent kits as indicated by
the manufacturer’s instructions.
2.3.4 Tumor necrosis factor -α (TNF-α)
Tumor necrosis factor α was
determined by in vitro Enzyme Linked
Immunosorbent Assay [ELISA] kit, using
colorimetric reaction method as instructed in
the kit manual.
2.3.5 Estimation of GSH, CAT, and lipid
peroxidation in liver tissue GSH and CAT activities were
determined by spectrophotometric method
(Beutler et al., 1963 and Aebi, 1984
respectively). Lipid peroxidation level was
measured by the thiobarbituric acid reaction
(Ohkawa et al., 1979).
2.3.6 Histopathological examination For light microscopic examination,
liver specimens were fixed Bouin's fluid,
dehydrated, cleared and embedded in
paraffin. Thin serial sections (5 μm) were cut
and stained with H&E for general studies and
Masson’s trichrome stain for collagen
demonstration. All the aforementioned
fixatives and stains as outlined by Bancroft
and Gamble (2008). For Transmission
electron microscopic (TEM) examination, the
collected liver specimens were cut in very
small pieces (1mm3) and fixed in 4%
gluteraldehyde solution (Hayat, 1986). They
were then post-fixed in 1% osmium tetroxide,
dehydrated and embedded in Epoxy medium.
Ultrathin sections were cut, stained with
uranyl acetate and lead citrate (Reynolds,
1963) and then examined by using
transmission electron microscope JEOL
(JEM-1400 TEM 80 kv) in the electron
microscope unit of faculty of Agriculture,
Cairo University.
2.4 Statistical analysis
All data are expressed in mean ±
standard errors. A statistical analysis was
performed by analysis of variance (ANOVA)
followed by a Tukey’s tests using GraphPad
Prism (GraphPad, San Diego, CA). For all
the statistical tests, the level of significance
was fixed at P< 0.05.
RESULTS Oral glucose tolerance test
In the OGTT (Fig. 1), the mean
values of fasting glucose was significantly
elevated in all treated mice when compared
to control. A rise in blood glucose level was
observed in all mice groups after 30 min
from glucose administration. The Fructose
fed mice exhibited delayed glucose clearance
and the glucose value was elevated at all the
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
106
time points as compared to control. While,
treatment with cinnamon at dose of 150
(mg/kg) significantly enhanced glucose
clearance as compared with fructose-alone
given group. Administration of cinnamon in a
dose of 300 (mg/kg) significantly lowered the
glucose level compared with fructose group;
however they failed to reach to the normal
level.
Body and liver weight:
The changes in body weight of the
mice during the 8weeks did not differ
significantly between groups (Table 1 ). No
significant changes in the mice liver weights
and the ratio of liver weight to body weight
were noticed after 8 weeks in the fructose fed
group.
Serum hepatic enzymes.
The activities of ALT, AST and ALP
enzymes showed no significant changes
among all groups (Table 2).
Blood glucose estimation
The levels of serum glucose was
significantly higher in fructose-fed mice as
compared to that of control. Co-
administration with cinnamon at dose rate of
150 mg/kg significantly reduced the levels of
glucose when compare to normal value
(Table 2).
Lipid profile
As shown in Table (2), there were
significant differences in the measured serum
lipid profile between the fructose-treated
mice and control group. Serum
concentrations of the total cholesterol,
triglyceride and LDL-C were decreased in
the cinnamon- treated groups than in the
fructose group. However, TC and LDL-C
values fails to return to normal in both doses
cinnamon treated mice. The level of HDL–C
was significantly decreased in fructose group,
but it found to be significantly higher in the
cinnamon treated groups compared to
fructose group.
Tumor necrosis factor -α
In fructose-fed mice significant
increase was observed in TNF-α value as
compared to control (Table 2). Treatment
with cinnamon at dose rate of 150 mg/kg
prevented that increase and brought it back
the level to normal level. But, in mice group
that treated with cinnamon at dose of 300
mg/kg the TNF-α value failed to return to
normal.
Hepatic antioxidants enzyme and lipid
peroxidation.
The activities of antioxidant enzymes
are shown in Table (2). The mice in fructose
group exhibited a significant decrease in
hepatic GSH and CAT activities compared
with the control group. Co-treatment with
150 mg/kg of cinnamon caused a significant
increase of GSH and CAT activities
compared with the activity in mice fed the
fructose only. However, GSH activity in
cinnamon group at dose rate of 300 mg/kg
was non- significantly increased than fructose
group and still significantly lower as
compared to control.
Figure (1): Glucose tolerance test at different
time. The data are given as means ± standard
error (SE). C= control, fructose, F= Fructose;
FC 150= fructose +Cinnamon dose of 150
mg/kg and FC 300= fructose +Cinnamon dose
of 300 mg/kg.
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
107
Table (1): Results of body weight from beginning of experiment till 8 weeks; liver weight
and ratio of liver weight to body weight of all mice groups.
The data are given as means ± standard error (SE), C= control, fructose, F= Fructose; FC 150= fructose
+Cinnamon dose of 150 mg/kg and FC 300= fructose +Cinnamon dose of 300 mg/kg.
Table (2): Effect of high fructose diet and cinnamon on glucose, hepatic enzymes, lipid
profile, TNF-α and hepatic antioxidant enzymes (M±SE).
The data are given as means ± standard error (SE), with dissimilar superscript letters (significantly differ at
p < 0.05): (a) letter is significantly differing from control value; (b) letter is significantly differing from
fructose group. n = 20/group. C, F, , FC 150 and FC 300 represent control, fructose, fructose +Cinnamon dose
of 150 mg/kg and fructose +Cinnamon dose of 300 mg/kg, respectively.
C F FC 150 FC 300
Body weight
(g)
1st week 20.00± 0.71 24.20±1.98 23.80 ±1.46 21.20±0.73
2nd
week 22.40±1.75 27.20±1.02 26.40±1.44 23.20±0.58
3rd
week 30.40±1.44 33.40±1.40 31.60±0.93 29.60±0.51
4th
week 31.60±1.54 34.00±1.52 31.20±0.86 32.40±0.75
5th
week 32.60±1.22 34.40±1.01 31.80±1.17 32.60±0.51
6th
week 33.00±0.92 35.20±0.98 32.40±0.93 33.20±0.87
7th
week 33.60±1.03 36.40±0.68 34.00±0.71 34.40±0.51
8th
week 34.50±0.68 37.30±0.85 35.40±0.40 34.60±0.68
Liver weight
Absolute (g) 1.58± 0.19 1.84±0.05 1.66±0.04 1.62±0.04
Relative (%)
4.58±0.50 4.93±0.16 4.69±0.11 4.68±0.05
Parameters C F FC 150 FC 300
Glucose (mg/dl) 103.7 ±5.6 135.9± 4.8a 106.6± 5.8
b 115.2± 4.6
AST (U/ml) 44.50±3.4 53.27±4.1 45.77±3.3 52.83±3.2
ALT (U/ml) 29.17±0.89 30.20±0.78 29.50±0.74 30.67±0.92
ALP (IU/l) 108.4±5.3 122.9±3.8 112.0±5.1 115.6±4.9
TC (mg/dl) 86.11±4.3 134.1±4.6 a 114.9±4.7
ab 116.8±4.1
a
TG (mg/dl) 72.65± 1.68 100.8± 3.59a 79.16± 3.27
b 82.65± 2.64
b
HDL-c (mg/dl) 49.3±3.5 35.8±2.3a 48.09±3.9
b 41.40±1.9
LDL-c (mg/dl) 22.31±4.87 78.04±3.38a 51.02±2.77
ab 59.02±4.24
ab
TNF-α (pg/ml) 27.44±0.80 43.03±1.97a 31.67±0.87
b 35.30±1.83
ab
GSH (U/g tissue) 2.87±0.04 1.27±0.22a 2.13±0.13
ab 1.76±0.09
a
CAT (U/g tissue) 1.82±0.15 0.88±0.08a 1.68±0.16
b 1.28±0.12
MDA (U/g tissue) 12.46±0.39 19.81±0.45a 11.19±0.33
b 11.83±0.75
b
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
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Histopathological examination
By light microscope, liver of control
showed normal architecture, the hepatocytes
(large, polygonal cells and some were
binucleated) arranged as hepatic cords
radiating from central veins and alternating
with blood sinusoids (Fig. 2.A). Stained
sections with Masson trichrome technique
revealed minimal amount of collagen fibers
around the central veins, hepatocytes and
periportal hepatic area (Fig. 2.B). With
electron microscope, the hepatocytes
cytoplasm contained rounded mitochondria,
well developed Golgi apparatus, rough
endoplasmic reticulum and smooth
endoplasmic reticulum. Their nuclei were
euchromatic with prominent nucleoli (Fig.
2.C). Marked histological changes were
observed in fructose group. The hepatocytes
showed degeneration (Fig. 3.A), marked fatty
change which exhibited by large vacuoles
pushing the nucleus toward the periphery of
the cell (Fig. 3.B) and cloudy swelling.
Degenerated hepatocytes with pyknotic
nuclei were seen and some cells had lost their
nuclei. Congested central vein; blood
sinusoids with von kupffer cells hyperplasia;
and diffuse and focal inflammatory cells
infiltration were recognized (Fig. 3.C). An
increase in the collagen fibers around the
central vein and in the periportal hepatic area
(Fig. 3.D).
With electron microscopy, the
hepatocyte revealed decrease in cytoplasmic
organelles, increasing fat globules and the
nuclei appeared heterochromatic (Fig. 3.E).
The liver of cinnamon at dose of 150 mg/kg
showed great improvement. However,
hyperplasia of von kupffer cells and
congested central vein were still noticed (Fig.
4.A). Collagen content became few (Fig.
4.B). Moreover, marked improvement was
seen in the hepatocytes by electron
microscopy. Reappearance of cytoplasmic
organelles and the nuclei were euchromatic
(Fig. 4.C). The liver of mice treated with 300
mg/kg of cinnamon were incompletely
improved. Most of hepatocytes surrounding
the central vein appeared with normal
histological profile. While that located more
peripherally showed vacuolar degeneration,
fatty change and some cells appeared with
pyknotic nuclei (Fig. 5. A).
Collagen content was similar to the
150 mg/kg of cinnamon and control group.
At the electron microscopical level, some
hepatocytes still occupied by fat globules
with decreasing in cytoplasmic organelles
(Fig.5.B).
DISCUSSION
High fructose feeding is commonly
used to induce a strong response on
metabolic parameters. In this study we aimed
to assess the regulatory effect of cinnamon
with different doses on metabolic disorders in
high fructose-fed mice.
Fructose is a highly lipogenic sugar
which is associated with a rapid stimulation
of lipogenesis and an increase of triglycerides
due to its metabolic pathway. In liver, the
most of ingested fructose is metabolized and
converted into glyceraldehyde-3-phosphate
(Tsuchiya et al., 2013).
Numerous studies demonstrated the
association between high fructose diet and
increase of weight gain. El Hasnaoui et al.
(2015) noticed an increase in rat body and
liver weight after feeding high fructose diet
(23%) for 12 weeks. This is not observed in
our study, as body and liver weight data don’t
show any significant changes between treated
groups and control. Consistent with our
results, Tillman et al. (2014) did not record
any significant differences in body weights
between mice fed on high-fructose diet for 14
week and the control.
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
109
We observed impaired glucose
tolerance after the oral glucose load in
fructose-fed mice. Glucose tolerance was
improved in cinnamon at a dose rate 150 mg/
kg group at (t= 60 &120 min) compared with
the control group. Serum blood glucose
levels of the both cinnamon dose groups (150
and 300 mg/kg. b.w) were decreased
compared with the fructose group. Similarly,
Ping et al. (2010) had reported that blood
glucose level decreased after administration
of cinnamon extract at dose of 50 and 100
mg/kg for 35 days in diabetic mice. Yadav et
al. (2007) reported that insulin resistance is
developed after feeding fructose (21%) in
water to rats for 8 weeks. Insulin resistance is
a condition in which circulating insulin
decreases its response to skeletal muscle,
adipose tissues, and liver. The anti-
hyperglycemic effect of cinnamon may be
due to its stimulation of surviving cells to
release more insulin (El Hasnaoui et al.,
2015) and activation of the insulin signaling
(Qin et al., 2004).
In the present study, the measured
hepatic enzymes activities showed no change
among groups. This finding agreed with that
reported by Meeprom et al. (2011). On
contrary, Ismail, (2014) found that
administration of aqueous extract of
cinnamon in dose of 100 and 200 mg/ kg for
6 weeks reduce the elevated ALT and AST in
high fat diet-fed rats.
The current data showed an increase
of total cholesterol, triglycerides, LDL-c, in
the mice fed fructose compared to control
group. These results are consistent with a
previous report (El Hasnaoui et al., 2015).
Administration of cinnamon at both doses to
fructose fed mice resulted in regulation of
lipid metabolism. Consistent with our results,
Kim et al. (2006) and Ping et al. (2010) had
also reported that triglyceride and total
cholesterol levels were decreased, and HDL-
c level was increased in cinnamon treated
mice. This effect may be as a result of
improved insulin action in cinnamon-treated
mice or the direct role of cinnamon on lipid
metabolism by its strong lipolytic activity
(Kannappan et al., 2006).
In the present study, we demonstrated
that serum concentration of TNF-α that were
increased by the high fructose intake was
restored to basal level by cinnamon
supplementation at a dose rate of 150
(mg/kgb.w) not at 300 (mg/kg).There is a
possibility that large doses or chronic
ingestion of cinnamon powder may provide
an increased dose of oil components that may
cause adverse effects, such as inflammation
(Bickers et al., 2005). Abraham et al.,
(2010) mentioned that coumarin, a bioactive
agent present in high level in cinnamon, has
hepatotoxic and carcinogenic effect.
We have observed that the high
fructose intake is associated with increased
oxidative stress as we recorded a depletion of
GSH and CAT enzymes and increase of
MDA level in fructose fed mice when
compared with control. Some authors have
proposed that MDA content increases
significantly in hepatic tissue exposed to high
fructose (Zhang et al. 2013). Excessive
oxidative stress induces mitochondrial
dysfunction, which further disturbs lipid
metabolism and suppress insulin signaling.
On the other hand, the abnormal lipid
metabolism and impaired insulin sensitivity
will enhance oxidative stress (Tsuchiya et
al., 2013). We demonstrated that
administration of cinnamon at the dose of
150 mg/kg significantly increase the hepatic
GSH and CAT contents comparing with
fructose-fed mice. Both doses of cinnamon
were able to decrease MDA level as
compared to fructose-fed mice. This may
attributed to its antioxidant activity due to the
presence of cinnamate (Lee et al., 2003),
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
110
Cinnamaldehyde, phenols and terpenes (Qin
et al., 2010) in the cinnamon bark.
In this study, we observed different
histological alterations in liver sections of
high fructose- fed mice especially in
hepatocytes around central veins as
hepatocellular vacuolation accompanied by
fatty change. That's augmented by electron
microscopy as hepatocyte's cytoplasm
occupied by lipid globules with decreasing in
cytoplasmic organelles. This finding agreed
with that revealed by Schultz et al., (2015),
Prabhakar et al., (2014) and Bradbury and
Berk (2004) who reported that the hepatic
fatty change occurs when the rate or
synthesis of fatty acids by hepatocytes
exceeds the rate of export or catabolism. In
the present study, local and diffuse
inflammatory cells infiltration with von
kupffer cell hyperplasia and congestion of
central veins were recorded. Some authors
(Anstee and Goldin, 2006) presented similar
findings. They stated that increasing in the
inflammatory response occurs as a result of
liver sensitivity for liver fatty change. Some
proliferated collagen fibers were observed
around central vein and periportal hepatic
area as recorded by El Ebiary and Khalaf
(2014). Liver fibrogenesis is occurred in
response to liver injury (Zhao et al. 2012).
So we agreed with the results reported that
fructose was considered as high risk factor in
developing nonalcoholic fatty liver disease
(NAFLD).Our results revealed that co-
administration with cinnamon at dose rate of
150 mg/kg b.w ameliorated the deleterious
effect of fructose on the structure of mice
liver. Most of hepatocytes improved and
appeared as similar to the control group
except some signs of von kupffer hyperplasia
with congested central vein. This
hepatocellular improvement appeared by
electron microscopy which manifested by
disappearance of accumulated lipid droplets,
reappearance of numerous well developed
cytoplasmic organelles. Such results could be
related to the lipolytic, antioxidant and anti-
inflammatory effect of cinnamon (El Ebiary
and Khalaf, 2014 and Yang et al.
2012).While, the liver structure in mice
group treated with 300 mg/kg was not
markedly improved as compared to the lower
dose of cinnamon. Some degree of
degenerations was recognized in our study
with light and electron microscopical
examination. Some of hepatocytes were
vacuolated associated with fatty change and
others had pyknotic nuclei.
In conclusion, the results of this
study revealed that hyperglycemia, lipid
profile disturbance accompanied with
oxidative injury, inflammation and liver fatty
change were induced by high fructose fed in
mice. Co-treatment with cinnamon resulted
in improvement of metabolic disorders and
cinnamon intake at dose of 150 mg/kg was
more effective than the higher dose of 300
mg/kg.
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
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Fig.2 : A. a photomicrograph of control mice liver showing normal architecture with radiating and
branching hepatic cords from thin walled central vein (CV) separated by blood sinusoids (S) lined with
endothelial cells and von kupffer cells (arrows), polyhedral hepatocytes with granular acidophilic
cytoplasm housing rounded vesicular nuclei. Notice, some cells were binucleated (arrowheads). H&E
stain, 400X. B. showing minimal amount of collagen fibers around central veins (arrow heads) and
periportal hepatic area (arrows). Masson's trichrome stain, 100X. C. An electron micrograph showing
hepatocyte had numerous mitochondria with cristae (m), well developed Golgi apparatus (G), RER (r)
SER (SR). Notice, euchromatic nucleus (N) with prominent nucleoli (n).5800X
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
112
Fig.3: A. a photomicrograph of high fructose fed mice liver showing dilated central vein (CV)
surrounded by affected and degenerated hepatocytes. H&E stain, 100X. B. A higher
magnification of (Fig.2.A) showing vacuolar degeneration of affected hepatocytes with marked
fatty change (arrows). H&E stain, 400X. C. Another section of mice liver showing congested
central veins (CV), diffuse inflammatory cell infiltration (arrows), hepatocytes with cloudy
swelling (double arrows) while others contained pyknotic nuclei (arrowheads). H&E stain,
400X.D. showing apparent increase of collagen fibers around central vein and in the periportal
hepatic area (arrows). Masson's trichrome stain, 100X. E. An electron micrograph showing
accumulation of lipid globules (L) in hepatocyte's cytoplasm, decreasing in cytoplasmic
organelles, housing heterochromatic nucleus (N).1000X.
EGYPT. J. COMP. PATH &CLINIC PATH. VOL. 28 NO.1, 2015 ; 103- 116
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Fig.4: A photomicrograph of mice liver fed on fructose and cinnamon 150mg/kg.bw A.showing
great improvement in hepatic architecture as similar to the control group except increasing of
von kupffer cells and congested central veins were present. H&E, 400X. B. showing collagen
fibers returned to be few as the control group. Masson's trichrome stain, 100X. C. An electron
micrograph showing marked improvement with normal hepatocyte's structure. Notice,
euchromatic nucleus (N), numerous mitochondria (m) well developed Golgi apparatus (G) RER
(R) and SER (SR). 7500X.
Fig.5: a photomicrograph of mice liver fed on fructose and cinnamon 300mg/kg.bw showing A.
incomplete improvement compared to the control group, some hepatocytes contained pyknotic
nuclei (arrows) and marked fatty change (arrow heads). H&E, 400X. B. an electron micrograph
showing some hepatocytes accumulated with lipid droplets with few cytoplasmic organelles.
5000X.
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