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2094
Personal non-commercial use only. EJH copyright © 2023. All rights served DOI: 10.21608/ejh.2022.157628.1756
Original
Article
A Comparative Study of the Toxic Effects of Monosodium Glutamate
and Sunset Yellow on the Structure and Function of the Liver,
Kidney, and Testis and the Possible Protective Role of Curcumin
in Rats
Walaa G. Abdelhamid1, Mahmoud B. Abdel Wahab2, Mona E. Moussa1,
Lobna A. Elkhateb3 and Doaa R. Sadek3
1
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Ain Shams
University, Egypt.
2
Department of Biochemistry, Poison Control Center, Ain Shams University Hospitals, Cairo, Egypt.
3
Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
ABSTRACT
Introduction: Monosodium glutamate (MSG) and sunset yellow (SY) are food additives that cause oxidative stress in body
tissues. Curcumin has many therapeutic activities including antioxidant, anti-inflammatory, and antitumor properties.
Aim of the Work: This study aimed to compare the toxic effects of monosodium glutamate (MSG) and sunset yellow (SY) on
the structure and function of multiple organs and to evaluate the possible protective effect of curcumin.
Material and Methods: Sixty adult male albino rats were divided into six groups. Group I (control). Group II received
curcumin. Group III received MSG; group IV received SY. Group V received MSG with curcumin, and group VI received
SY with curcumin. All treatments were given daily to rats by oral gavage for 28 days. Blood samples were obtained for
biochemical analysis at the end of the experiment. The liver, kidney, and testis were dissected for histological studies.
Results: Monosodium glutamate, and to a lesser extent SY caused a significant increase in body weight and protein
carbonyl levels with a significant elevation in liver enzymes, total bilirubin, and lipid profile. Sections in the liver showed
fatty degeneration, necrosis, and cellular infiltration. A significant increase in Caspase-3 positive immunoreactivity was also
detected. Glomerular atrophy, degenerated tubules, and a significant decrease of BCL-2 positive cells were recorded in the
kidney with significantly elevated urea, creatinine, and uric acid levels. In the testis, decreased height of germinal epithelium
was confirmed by a significant decrease in PCNA-positive cells, testosterone and LH levels. A significant increase in collagen
fibers deposition in the liver, kidney, and testis was noticed. Curcumin ameliorated the deleterious effects of MSG and SY on
the structure and function of the examined organs.
Conclusion: Monosodium glutamate had more toxic effects in comparison to SY. Supplementation with curcumin extract
could successfully ameliorate their toxic effects through its antioxidant action.
Received: 01 September 2021, Accepted: 11 October 2022
Key Words: Curcumin, monosodium glutamate, oxidative stress, protein carbonyl, sunset yellow.
Corresponding Author: Doaa R. Sadek, MD, Department of Histology, Faculty of Medicine, Ain Shams University,
Cairo, Egypt, Tel.: +20 10 0260 9026, E-mail: d.sadek@med.asu.edu.eg
ISSN: 1110-0559, Vol. 46, No. 4
INTRODUCTION
Food additives are substances that are added to foods
to enhance flavor, color, texture, nutritional value, and
preservation[1]. They are divided into preservatives, taste
enhancers, coloring agents, antioxidants, stabilizers, and
emulsifiers. It has been noticed that people, especially
children, consume food additives in great amounts due to
their wide availability, in many food products[2]. The sodium
salt of glutamic acid, monosodium L-glutamate (MSG),
has 78% glutamic acid and 22% sodium salt and water.
It is produced through molasses fermentation from sugar
cane or sugar beets, corn sugar, and starch. It is composed
of white odorless crystals readily soluble in water[3]. It is
the most common food additive used as a flavor enhancer
since 1907 with trade names such as Ajinomoto, Chinese
salt, and E621[4]. It does not decompose during food
processing or cooking; however, it is partially dehydrated
and transforms into pyrrolidone-2-carboxylate in hot and
acidic environments. It is commonly used in many food
products such as chips, noodles, canned soups, flavored
flakes, mutton meat, bottled soy or Eastern sauces, and
frozen and tested tuna[5]. Monosodium glutamate breaks
down in an aqueous solution, releasing free glutamate.
Free glutamate attaches to taste receptors in the mouth
and activates taste nerves to produce the distinct umami
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Abdelhamid et. al.,
flavor, which is different from the four basic sensations
of sour, salty, sweet, and bitter[6]. Monosodium glutamate
is recognized by the WHO and FDA as a safe food
ingredient with no established daily upper intake limit[7].
However, Freeman reported that overconsumption of
MSG in restaurants resulted in a complex of symptoms
termed ‘Chinese restaurant syndrome, including dizziness,
weakness, numbness, flushing, and headache[8].
Sunset Yellow (SY), identified by E110, is a synthetic
yellow azo dye produced from aromatic petroleum
hydrocarbons. It is used as a food coloring in foods
including dairy products, snack chips, jams, dry drink
powders, orange sodas, margarine, ice creams, chocolates,
and cake decorations[9]. It is also used in aqueous drug
solutions, tablets, capsules, toothpaste, and cosmetics[10].
Even though they are often used, azo dyes are currently
regarded as one of the most toxic food additives[11].
However, the available literature regarding their toxicity is
still insufficient and quite contradictory with limited work
evaluating their cytotoxicity[12]. Currently, SY is forbidden
in some countries such as Norway and Finland; however, it
is still widely used in many countries including Egypt and
the Arab world without any regulations[13].
The usage of natural medicinal plants to lower
toxicities has grown in recent years all around the
world. Curcumin is an essential component of the plant's
rhizomes, Curcuma longa, which belongs to the family
(Zingiberaceae)[14]. Curcumin has received a lot of
attention lately because it exhibits various therapeutic
activities including antioxidant, anti-inflammatory, and
antitumor properties[15]. Considering the discrepancies in
the literature and the growing safety concern for the use
of food additives, the present study aimed to compare the
toxic effects induced by MSG and SY on the structure and
function of the liver, kidney, and testicles in adult male
albino rats and to evaluate the possible protective role of
curcumin in ameliorating these abnormalities.
MATERIALS AND METHODS
Chemicals
Monosodium glutamate salt (C5H8NNaO4), purity
purchased from Sigma-Aldrich, USA. MSG, SY, and
curcumin powder were then administered after being
dissolved in distilled water. All additional compounds were
of a high analytical grade.
Experimental animals and ethical approval
Sixty adult male albino rats, weighting about 150±20g
were obtained from the Clinical Research Centre of the
Faculty of Medicine, Ain Shams University, Egypt. They
were kept in typical laboratory settings with a 12-hour
light/dark cycle and were given unlimited access to food
and tap water. The study was approved by the Faculty
of Medicine, Ain shams University Research Ethics
Committee [FMASU (R 143) 2022].
Experimental design
The rats were divided randomly into six equal groups
following a two-week acclimatization period, as follows:
Group I: Distilled water (D.W.) group (negative
control): rats were kept under normal conditions and
received distilled water (1mL/100g body weight/day).
Group II: Curcumin (Cur) group: rats received
curcumin (150 mg/kg body weight/day)[16].
Group III: MSG group: rats received MSG (600 mg/
kg body weight/day)[17].
Group IV: SY group: rats received SY (200 mg/kg
body weight/day)[18].
Group V: MSG+Cur group: rats received MSG (as in
group III) and curcumin (as in group II).
Group VI: SY+Cur group: rats received SY (as in
group IV) and curcumin (as in group II).
All treatments were given orally for 28 days.
Collection of blood samples
Prior to scarification and before the beginning of the
trial, all rats were weighted. At the end of the experiment
(after the 28-day treatment), rats were sacrificed by
cervical dislocation. Glass tubes were used to collect the
blood samples, which were then centrifuged for 15 minutes
at 4000 rpm after being allowed to coagulate. Serum was
then stored at -80ºC for biochemical assay. The following
parameters were estimated using Arena Bioscien kits,
Egypt.
Hepatic, renal profile, and lipid profiles
Serum ALT and AST were determined by Reitman
and Frankel[19] and Murray[20]
glutamyltransferase (GGT) activity was measured by
Saw et al.[21]. Serum total bilirubin and albumin were
performed by Walter and Gerade[22] and Doumas et al.[23]
respectively. Serum urea concentration was measured
by Fawcett and Scott[24]. Serum creatinine and uric acid
concentration were estimated by Larsen[25] and Caraway[26],
respectively. Measurements of lipid profile (triglycerides,
LDL-cholesterol, HDL-cholesterol, and total cholesterol
concentrations) were done according to Ibegbulem et al.[27].
Determination of testosterone and luteinizing hormone
(LH) concentrations
Testosterone hormone level was measured by ALPCO
(NH, USA) Elisa kit by Wheeler[28], and LH was determined
using Abnova (Taipei, Taiwan) ELISA kit by Kosasa[29].
Determination of protein carbonyl
Serum protein carbonyl (PC) concentration was
determined according to the method described by Fields
and Dixon[30] where DNPH (Brady’s reagent) reacts with
aldehyde and ketone groups producing DNP-hydrazone.
The distinct UV absorption of DNP-hydrazone was
measured using a spectrophotometer at 370 nm. After
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FOOD ADDITIVES AND CURCUMIN
derivatization, protein carbonyls were quantified by
measuring absorbance at 370 nm and calculating hydrazone
concentration using molar extinction coefficient (22000 M
1 cm 1) for dinitro-phenyl hydrazone/mg of protein.
Sample collection for histological studies
The liver, kidney, and testicles were removed from the
animals after scarification. They were then immediately
preserved in 10% buffered formalin and processed to
create paraffin blocks. Hematoxylin and eosin (H and E),
Masson's trichrome, and Periodic acid Schiff's reaction
(PAS) were used to stain sections cut at a thickness of
5-7µm.
Immunohistochemical studies
A positive-charged slide was used to cut the paraffin
sections and were subjected to immune histochemical
reaction using an anti-Caspase-3 antibody (Lab Vision,
CA, USA.) to detect apoptosis in the liver cells, anti-B-
cell lymphoma antibody (BCL-2) (mouse monoclonal
antibody- from SIGMA-ALDRICH) to detect anti-apoptotic
reaction in the kidney and proliferating cellular nuclear
antigen (anti PCNA) (Mouse-anti-human polyclonal
antibody, Santa Cruz Biotechnology Dallas Texas USA)
to detect the proliferation of the germinal epithelium of
the seminiferous tubules. The sections were exposed to a
secondary antibody (DAKO, Denmark) for 30 minutes.
DAB solution (DAKO, Denmark) was used to develop the
reaction for 10 minutes. The slides were then dehydrated,
cleaned, and mounted after being counterstained with
hematoxylin. The identical procedure was followed while
processing negative controls, with the exception of using
the primary antibody. Positive reaction: Caspase-3: brown
cytoplasmic reaction. BCL-2: brown cytoplasmic reaction.
PCNA: brown nuclear reaction.
Morphometric analysis
It was done on a computer in the Histology and Cell
Biology Department, Faculty of Medicine, Ain Shams
University, using the image analyzer Leica Q win V. 3
program. A Leica DM2500 microscope (Wetzlar, Germany)
was linked to the computer. All specimens were subjected
to morphometric analysis. Using three separate slides from
each animal, measurements were taken (X40). On each
slide, the measurement was performed on five randomly
chosen non-overlapping fields to measure the mean of the
following:
The liver
i. Area percentage of collagen fibers in the liver
using Masson’s trichrome stain.
ii. Area percentage of liver glycogen in PAS sections.
iii. The number of caspase-3 positive hepatocytes.
The kidney
i. Area percentage of collagen fibers in kidney using
Masson’s trichrome stain.
ii. The optical density of BCL-2 in the kidney
sections.
The testis
i. The thickness of germinal epithelium (µm) in
H&E sections of the testis.
ii. Area percentage of collagen fibers in testis using
Masson’s trichrome stain.
iii. The thickness of the basement membrane in the
testis in PAS sections.
iv. The number of PCNA-positive spermatogenic
cells.
Statistical analysis
By using version 23 of the Statistical Package for the
Social Sciences (SPSS Inc., Chicago, IL, USA), all statistical
analyses of biochemical blood tests and histomorphometric
studies were carried out. The experiment's findings were
presented as mean values and standard deviations. A one-
way analysis of variance (ANOVA) was used to assess the
significant differences in values, and then a post-doc Tukey
multiple comparisons test was used to further analyze
the changes between the groups. For all comparisons,
P-value < 0.05 was considered significant.
RESULTS
Body Weight Gain
Monosodium glutamate- and SY-treated rats showed a
significantly higher body weight gain (P<0.05) compared
with control rats. While concomitant treatment with
curcumin caused a significant reduction in weight gain. No
significant change was observed in the body weight of rats
concomitantly treated with SY and curcumin compared to
controls. (Table 1)
Serum protein carbonyl (PC) levels
A significant elevation in PC levels (P<0.05) was
observed in MSG- and SY-treated rats compared to
all other groups. This was also noticed in the MSG-
treated group compared to the SY-treated group.
Monosodium glutamate+cur group showed a significant
reduction in PC levels compared to MSG group.
However, no significant change in PC levels was seen in
SY+cur group compared to control groups. (Table 2)
Hepatic profile
Monosodium glutamate and SY caused a significant
increase in ALT activity compared to all other groups.
On the other hand, groups concomitantly treated with
curcumin showed a non-significant increase in ALT
activity compared to control groups. Administration of
MSG or SY resulted in a highly significant increase in AST
activity as compared to other groups while concomitant
administration of curcumin with SY showed a non-
significant increase in AST activity compared to controls.
A significant increase in GGT activity and total bilirubin
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Abdelhamid et. al.,
was also noticed in MSG- and SY-treated rats compared
to other groups. Co-administration of curcumin with MSG
or SY significantly decreased the values of GGT and total
bilirubin when compared to those received MSG or SY
alone. Albumin levels were significantly decreased in MSG-
treated rats compared to other experimental groups. (Table 3)
Renal profile
A significant elevation in serum urea concentration
was recorded with the administration of MSG and SY
compared to other groups. Concomitant administration
of curcumin resulted in a significant decrease in serum
urea levels compared to MSG- and SY-treated groups.
Monosodium glutamate and SY also caused a significant
increase in serum creatinine concentration compared to
all other groups. A significant decrease was recorded in
serum creatinine levels in rats that received curcumin in
addition to MSG or SY compared to rats that received
MSG and SY alone. A significant increase in serum uric
acid concentration in MSG- and SY-treated rats was also
noticed compared to other experimental groups with no
significant change in that co-administered curcumin with
MSG and SY when compared to control groups (Table 4).
Lipid profile
Administration of MSG and SY caused a significant
elevation in serum triglycerides concentrations compared to
other groups. Also, LDL concentrations were significantly
increased in MSG- and SY-treated rats compared to control
groups. Monosodium glutamate data showed a highly
significant decrease in HDL concentration compared to
other groups. Total cholesterol levels were significantly
increased in MSG and SY groups with a significant
decrease observed upon administration of curcumin in
addition to MSG and SY. (Table 5)
Hormonal profile
The mean serum testosterone and LH levels were
significantly lower in MSG- and SY-treated rats compared
to control groups, with a significant decrease in the MSG
group compared to the SY group. No significant difference
was shown in serum testosterone and LH levels of the
SY+Cur group when compared to control groups (Table 6).
Histological Results
Examination of the histological sections of the curcumin
group (data not shown) showed similar results to that of the
negative control group.
Liver sections
The examination of sections stained with hematoxylin
and eosin (H&E) of the control group showed normal
hepatic architecture. The liver consisted of hepatic lobules.
Central veins were seen in the center of the hepatic lobules
with cords of hepatocytes radiating from them. These cords
were separated by narrow blood sinusoids. The hepatocytes
appeared polygonal in shape with central rounded vesicular
nuclei and acidophilic cytoplasm. Some hepatocytes were
binucleated. Portal tracts were located at the periphery
of hepatic lobules and contained branches of the hepatic
artery, portal, vein, and bile duct (Figure 1A). In the MSG
group, the liver architecture was disturbed with dilated and
congested blood sinusoids. Many hepatocytes appeared
vacuolated with fatty degeneration; others appeared with
pyknotic nuclei. Mononuclear cellular infiltration was
frequently seen around most central veins. In addition, many
oval cells were noticed in the proliferating bile ductules in
the portal areas (Figure 1B). The liver sections of the SY
group showed dilated congested, central veins with ruptured
endothelial lining. Many hepatocytes appeared vacuolated;
others appeared with pyknotic nuclei. The blood sinusoids
were frequently seen congested and dilated (Figure 1C).
Concomitant administration of curcumin together with
MSG- and SY- showed an almost normal appearance of the
hepatocytes. However, some hepatocytes showed necrotic
changes with some dilated and congested blood sinusoids
(Figures 1 D,E). In the MSG+Cur group, mononuclear
cellular infiltration was occasionally seen around central
veins (Figure 1D).
Masson’s trichrome-stained sections
The control group showed few collagen fibers around
the central vein and the portal tract and in-between the
hepatic cords (Figure 1F). In MSG and SY groups, an
increased amount of collagen fibers was noticed around
the CV, portal tracts and in between hepatic cords (Figures
1 G,H). While concomitant administration of curcumin
with MSG and SY showed few collagen fibers around
CV, portal tracts, and in between hepatic cords (Figures
1 I,J) respectively. These results were supported by the
histomorphometric data. A significant increase (P<0.05) in
the mean area percentage of collagen fibers in MSG and
SY groups compared to control groups. While a significant
decrease was noticed in Monosodium glutamate+Cur
and SY+Cur groups compared to MSG and SY alone
(Table 7).
Periodic acid Schiff- stained sections (PAS)
In the control group, most hepatocytes showed a
strong PAS-positive reaction (Figure 2A). In MSG and
SY groups, decreased PAS reaction was noticed in most of
the hepatocyte’s cytoplasm (Figures 2 B,C). Monosodium
glutamate+Cur and SY+Cur groups showed many
PAS-positive granules in most of the cytoplasm of the
hepatocytes, while few hepatocytes were still seen with
weak PAS reaction (Figures 2 D,E) respectively. Also,
histomorphometric results showed significant decrease in
the mean area percentage of liver glycogen in MSG and
SY groups compared to the control group. In MSG+Cur
and SY+Cur groups; a significant increase in the mean area
percentage of liver glycogen compared to Monosodium
glutamate and SY groups was detected (Table 7).
Immunohistochemical stain (Caspase-3)
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FOOD ADDITIVES AND CURCUMIN
The examination of Caspase-3 sections of the control
liver showed a negative reaction in the cytoplasm of
hepatocytes (Figure 2F). However, in the MSG group,
most hepatocytes showed a strong positive Caspase-3
reaction (Figure 2G). In the SY group, a moderate number
of hepatocytes showed a positive Caspase-3 reaction
(Figure 2H). In rats that received curcumin with MSG and
SY, mild Caspase-3 reaction was occasionally noticed in
hepatocytes (Figures 2 I,J) respectively. Statistical analysis
showed a significant increase in the number of hepatocytes
with positive Caspase-3 reaction in MSG and SY groups
compared to control groups. A significant decrease was
noticed in MSG+Cur and SY+Cur groups compared to
MSG and SY groups respectively (Table 7).
Kidney sections
The examination of H&E-stained sections of the control
kidney showed normal glomeruli with an intact Bowman’s
capsule and filtration space. Proximal convoluted tubules
(PCTs) had rounded small outlines and narrow lumina,
and distal convoluted tubules (DCTs) appeared with
large oval outlines and wide lumina (Figure 3A). In the
MSG group, atrophy of glomeruli was frequently seen.
Some renal tubules appeared with vacuolated epithelial
lining. Dilatation and congestion of peritubular capillaries
(Figure 3B). In the SY group, glomerular atrophy was
accompanied with an apparent increase in the number of
extra glomerular mesangial cells (Figure 3C). Concomitant
administration of curcumin resulted in amelioration of the
effects of MSG and SY on the kidney structure. Renal
glomeruli and tubules appeared normal. However, some
renal glomeruli in the MSG+Cur group were still affected
(Figures 3 D,E).
Masson’s trichrome-stained sections
In the control group, few scattered collagen fibers
were seen around the renal corpuscle and renal tubules
(Figure 3F). Increased collagen fiber deposition was
noticed intraglomerular and in the interstitium in MSG
and SY treated groups (Figures 3 G,H) respectively. While
Collagen fibers deposition was decreased with concomitant
administration of curcumin in MSG+Cur and SY+Cur
groups (Figures 3 I,J) respectively. This was confirmed by
significant (P<0.05) increase in the mean area percentage
of collagen fibers in MSG and SY groups compared to
control groups and a significant decrease in MSG+Cur and
SY+Cur groups compared to MSG and SY alone (Table 8).
Periodic acid Schiff- stained sections (PAS)
PAS-stained kidney sections of the control group
revealed prominent PAS-positive reaction in basement
membranes of renal corpuscles and tubules, brush borders
of PCT and mesangial matrix in glomerular corpuscle
(Figure 4A). In MSG and SY groups, PAS reaction revealed
thickened glomerular and tubular basement membranes
and decrease PAS positive mesangial matrix in MSG.
In SY treated group, prominent PAS positive mesangial
matrix was detected. Decrease in PAS positive brush
border of PCT was detected in MSG and SY treated groups
(Figures 4 B,C) respectively. In MSG+Cur and SY+Cur
groups, the PAS immunoreactivity appeared normal
especially in the SY+Cur group (Figures 4 D,E)
Immunohistochemical stain (BCL-2)
The examination of BCL-2 sections of control rats
showed positive expression of BCL-2 in some tubular
cells (Figure 4F). In MSG and SY groups, mild BCL-2
reaction was noticed in few tubular cells (Figures 4 G,H)
respectively. In MSG+Cur and SY+Cur groups, a moderate
reaction was noticed in many glomerular and tubular cells
(Figure 4 I,J) respectively. Similarly, statistical analysis
showed a significant decrease in the mean optical density
of BCL-2 in MSG and SY groups compared to control
groups. A significant increase in mean optical density of
BCL-2 was also noticed in MSG+Cur and SY+Cur groups
compared to control, MSG and SY groups (Table 8).
Testis Sections
The examination of sections of the control testis
showed closely packed seminiferous tubules with minimal
interstitium containing Leydig cells and blood vessels. The
germinal epithelium of seminiferous tubules was formed
of spermatogonia, primary spermatocytes, and early and
late spermatids. Sertoli cells were seen in between the
germinal epithelial cells, with many sperms attached
to their apical surface. The lumen of the seminiferous
tubules was filled with numerous spermatozoa. Germinal
epithelium and Sertoli cells were seen resting on regular
basement membranes that were surrounded by myoid cells
with flattened nuclei. (Figure 5A). However, in MSG
and SY-treated rats, there was a noticeable enlargement
of the interstitial spaces with congested blood vessels.
An apparent decrease in the number of Leydig cells was
also noticed. Decrease in thickness of germinal epithelium
with large gaps between the cells. Most spermatogenic
cells appeared degenerated with dense darkly stained
nuclei. (Figures 5 B,C) respectively. Co-administration
of curcumin with MSG and SY; resulted in more or less
normal Spermatogenic cells lining the seminiferous tubules,
whereas empty spaces were occasionally seen between
spermatogenic cells (Figures 5 D,E). These microscopic
findings were confirmed by a significant decrease (P<0.05)
in the thickness of the germinal epithelium in MSG and SY
groups compared to the control groups. On the other hand, a
significant increase was noticed in MSG+Cur and SY+Cur
groups in comparison to MSG and SY groups respectively.
No significant difference was noticed between-group the
SY+Cur group and the control group (Table 9).
Masson’s trichrome-stained sections
Minimal collagen fibers were noticed in the basal
lamina of the seminiferous tubules, and in the interstitium
of the control group (Figure 5F). In MSG and SY groups,
increased deposition of collagen fibers was noticed
(Figure 5 G,H) respectively. Collagen fibers deposition
was decreased in the groups treated with MSG and SY
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Abdelhamid et. al.,
concurrently with curcumin (Figures 5 I,J) respectively.
These results were supported by a significant (P<0.05)
increase in the mean area percentage of collagen fibers
in MSG and SY groups compared to control groups and a
significant decrease was noticed in MSG+Cur and SY+Cur
groups compared to MSG and SY alone (Table 9).
Periodic acid Schiff- stained sections (PAS)
In the control group, a PAS-positive reaction was
observed in the thin-walled blood vessels and the thin
basal lamina of the germinal epithelium. Acrosomal
caps of the spermatid showed PAS-positive reactions at
different stages of spermiogenesis up to mature sperms.
The caps appeared crescent and faced the Sertoli cells. The
glycocalyx of the mature sperms also showed PAS-positive
reactions (Figure 6A). In MSG and SY groups, the basal
lamina of the germinal epithelium appeared thickened and
detached, Absent acrosomal cap and weak PAS reaction
in the glycocalyx of mature sperms were also noticed
(Figures 6 B,C) respectively. On the contrary, MSG+Cur
and SY+Cur groups revealed normal PAS-positive reactions
similar to control groups (Figures 6 D,E) respectively. In
the same context, statistical analysis showed a significant
rise in basement membrane thickness in MSG and SY
groups in comparison to the control group while there
was a significant drop in groups MSG+Cur and SY+Cur
(Table 9).
Immunohistochemical stain (PCNA)
Examination of the control rats showed strong positive
PCNA immune reactions in nuclei of spermatogonia and
primary spermatocytes (Figure 6F). In rats treated with
MSG and SY, few cells showed mild positive PCNA
reaction (Figures 6 G,H) respectively. However, sections
of the testis treated with curcumin concurrently with MSG
and SY showed an increased number of PCNA-positive
cells (Figure 6 I,J) respectively. Sertoli cells and Leydig
cells exhibited negative PCNA reactions in all examined
groups. Similarly, statistical analysis showed a significant
decrease in the number of PCNA-positive nuclei in MSG
and SY groups compared to control groups. Moreover, a
significant increase in the number of PCNA-positive nuclei
was noticed in MSG+Cur and SY+Cur groups compared to
MSG and SY groups, respectively (Table 9).
Table 1:MSG and sunset yellow (SY) individually and in combination with curcumin on body weight of all experimental animals
Groups Initial body weight (g) Final body weight (g) Weight gain (g)
Negative control (D.W.) 150.3 ± 12.9 214.6 ± 11.4 64.3 ± 6.9
Cur 150.9 ± 12.5 214.7 ± 9.8 63.8 ± 6.7
MSG 148.1 ± 12.1 247.6 ± 14.1 ab 99.5 ± 6.9 ab
SY 150.9 ± 14.4 236.9 ± 13.9 abc 86 ± 6.1 abc
MSG+cur 149.1 ± 12.1 225.9 ± 6.1 abcd 76.8 ± 8.4 abcd
SY+cur 152.4 ± 12.3 222.6 ± 10.9 cd 70.2 ± 6.2 cde
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
group; (e) p< 0.05 vs. MSGMSG: MSG, SY: sunset yellow.
Table 2: MSG and sunset yellow (SY) individually and in combination with curcumin on serum protein carbonyl (PC) levels of
all experimental animals.
Groups
Negative control (D.W.) 5.8 ± 0.6
Cur 5.1 ± 1.1
MSG 20.5 ± 2.4 ab
SY 12.3 ± 1.4 abc
MSG+cur 8.6 ± 0.8 abcd
SY+cur 6.1 ± 0.8 cde
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
group; (e) p < 0.05 vs. MSGMSG: MSG, SY: sunset yellow.
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FOOD ADDITIVES AND CURCUMIN
Table 3:MSG
animals.
Groups ALT (IU/L) AST (IU/L) GGT(IU/L) Total bilirubin (mg/ dl) Albumin (mg/ dl)
Negative control (D.W.) 26.9 ± 5.4 126.6 ± 6.1 7.9 ± 2.2 0.33 ± 0.09 4.45 ± 0.3
Cur 25.3 ± 3.1 125.1 ± 8.8 8.1 ± 2.1 0.35 ± 0.09 4.49 ± 0.2
MSG 49.8 ± 5.9ab 230.5 ± 17.1ab 22.2 ± 3.3ab 0.83 ± 0.15ab 3.29 ± 0.2ab
SY 37.9 ± 1.8abc 166.6 ± 12.3abc 18.3 ± 2.6abc 0.58 ± 0.09abc 4.23 ± 0.1c
MSG+cur 30.3 ± 2.1cd 140.4 ± 4.3 abcd 11.3 ± 2.8 cd 0.39 ± 0.07 cd 4.42 ± 0.2 c
SY+cur 27.5 ± 4.6 cd 128.2 ± 8.3 cd 8.4 ± 2.1 cd 0.35 ± 0.07 cd 4.33 ± 0.24 c
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs.
MSG
group; (d) p < 0.05 vs. SY group. D.W:
MSG
:
MSG
Table 4: MSG
animals.
Groups Urea (mg/ dl) Creatinine (mg/ dl) Uric acid (mg/ dl)
Negative control (D.W.) 31.5 ± 6.4 0.74 ± 0.08 1.34 ± 0.11
Cur 31.9 ± 4.7 0.73 ± 0.11 1.31 ± 0.15
MSG 78.7 ± 9.5 ab 1.62 ± 0.22 ab 2.36 ± 0.13 ab
SY 50.1 ± 4.9 abc 1.24 ± 0.15 abc 1.71 ± 0.5 abc
MSG+cur 40.1 ± 4.7 abcd 0.92 ± 0.11 cd 1.32 ± 0.08 cd
SY+cur 36.4 ± 3.7 cd 0.78 ± 0.12 cd 1.33 ± 0.15 cd
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
group. MSGMSG: MSG, SY: sunset yellow.
Table 5:MSG
Groups Triglycerides (mg/dl)
Negative control (D.W.) 77.8 ± 5.4 31.1 ± 4.6 48.3 ± 5.7 77.4 ± 6.1
Cur 78.2 ± 5.7 31.4 ± 4.9 48.9 ± 7.1 78.5 ± 5.4
(MSG 114.3 ± 5.6 ab 82.3 ± 7.9 ab 32.2 ± 2.7 ab 120.9 ± 9.8 ab
SY 105.7 ± 4.2 abc 44.9 ± 8.1 abc 50.1 ± 3.1 c 90.7 ± 7.1 abc
MSG+cur 78.9 ± 6.2 cd 47.3 ± 5.7 abc 48.4 ± 4.8 c 84.1 ± 5.4 c
SY+cur 76.3 ± 6.1 cd 33.2 ± 3.7 cde 52.1 ± 3.1 c 78.7 ± 4.2 cd
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
group; (e) p < 0.05 vs. MSGMSG: MSG, SY: sunset yellow.
Table 6: MSG
experimental animals.
Groups LH (mlU/ml)
Negative control (D.W.) 1.89 ± 0.17 32.3 ± 1.46
Cur 1.94± 0.14 32.7 ± 0.79
MSG 0.73 ± 0.12ab 21± 2.1ab
SY 1.2 ± 0.07abc 25.56 ± 0.95abc
MSG+cur 1.6 ± 0.15 cd 29.9 ± 0.93cd
SY+cur 1.74 ± 0.14 cd 30.45 ± 1.66 cd
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
MSG: MSG, SY: sunset yellow, LH: Luteinizing hormone.
2101
Abdelhamid et. al.,
Table 7:MSG
liver of all experimental animals.
Groups Mean area % of glycogen Mean number of Caspase-3 positive cells
Negative control (D.W.) 1.43 ± 0.18 34.1± 3.04 2.4±1.1
Cur 1.35 ±0.78 34.73±2.17 2 ± 0.7
MSG 12.89±1.53ab 18.65±1.48ab 50.4±12.78ab
SY 9.83±1.28 abc 22.68±1.56abc 34.4±3.8abc
MSG+cur 2.7 ±0.67cd 31.88±3.33cd 14.2± 3.2abcd
SY+cur 1.73±0.52cd 33.92±1.32cd 9 ±2.1cd
Values are represented as mean ± SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group; (c) p < 0.05 vs. MSG group; (d) p < 0.05 vs. SY
MSG: MSG, SY: sunset yellow.
Table 8:MSG
kidney of all experimental animals.
Groups Mean optical density of BCL-2
Negative control (D.W.) 3.06 ±0.21 11.57±0.75
Cur 3±0.16 11.81±1.5
MSG 13.05±1.67 ab 3.07± 1.2 ab
SY 10.71±1.37 ab 4.8±0.51abc
MSG+cur 4.41 ±1.04 abcd 27.12±3.09 abcd
SY+cur 3.9 ±0.45d28.02 ±3.6 abcd
Values are presented as mean ±SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group, (c) p < 0.05 vs. MSG group, (d) p < 0.05, vs. SY
MSG: MSG, SY: sunset yellow, Cur: curcumin.
Table 9:MSG
Groups Mean area % of
Mean thickness of basement
membrane (PAS)
Mean number of PCNA-
positive germinal cells
Mean thickness of
germinal epithelium(µ)
Negative control (D.W.) 3.13±1.22 0.46±0.11 79.01±7.1 95.38±2.32
Cur 3.16±1.08 0.42± 0.08 80.37±6.5 96.06±3.52
MSG 10.8 ±2.7ab 1.5 ±0.16ab 38.00±2.54 ab 53.20±5.12ab
SY 8.92±1.25 abc 1.14 ±0.11abc 44±2.34abc 61.7±4.78 abc
MSG+cur 4.67 ±1.02cd 0.62 ±0.13cd 72.00±8.51cd 86.17±4.74 cd
SY+cur 4.04 ±0.45cd 0.58 ±0.18cd 74.60±3.91cd 90.9 ±5.59cd
Values are presented as mean ±SD. (a) p < 0.05 vs. control (D.W.) group; (b) p < 0.05 vs. curcumin group, (c) p < 0.05 vs. MSG group, (d) p < 0.05, vs. SY
MSG: MSG, SY: sunset yellow, Cur: curcumin.
2102
FOOD ADDITIVES AND CURCUMIN
Fig. 1:
radiating from the central vein. Hepatocytes are separated by the blood sinusoids (S). Hepatocytes appeared polygonal in shape with central rounded vesicular
vein (PV), and bile duct (D). [B] MSG
MSG
MSG
MSG+ Curcumin) and
2103
Abdelhamid et. al.,
Fig. 2:
MSG
treated groups with MSG
in hepatocytes. [G] MSG
MSG
2104
FOOD ADDITIVES AND CURCUMIN
Fig. 3:
appear with a large oval outline and wide lumina. [B] MSG
apparent increase in extra mesangial cells can be seen (white arrow). [D &E] curcumin+ MSG
MSG
MSG
seen after concomitant treatment the rats receive MSG and SY with curcumin respectively.
2105
Abdelhamid et. al.,
Fig. 4:
positive mesangium, positive basement membrane in renal corpuscles and tubules (thin arrow). A prominent brush border is also seen in renal tubules
(thick arrow). [B&C] MSG and SY groups respectively: showing thick PAS-positive basement membrane (thin arrow). A prominent increase in mesangial
MSGMSG and SY
respectively: preservation of basement membrane (thin arrow), increase in PAS-positive reaction of the mesangial matrix (GC), and brush border (thick arrow)
MSG & SY groups respectively: showing mild
cytoplasmic reaction in few tubular cells. [I&J] curcumin concurrently with MSG and SY respectively: increased number and density of BCL-2 positive cells
are seen in cells of renal glomeruli.
2106
FOOD ADDITIVES AND CURCUMIN
Fig. 5:
[B]: (MSG
spermatogenic cells. [D&E] curcumin with MSG
MSG
2107
Abdelhamid et. al.,
Fig. 6:
spermiogenesis up to mature sperm. The caps appear crescent and face the Sertoli cells. The glycocalyx of the mature sperms (curved arrow) also appears with
a PAS-positive reaction. [B&C] MSG
Areas of the detached basal lamina (curved arrow), absent acrosomal cap, and glycocalyx reactions are also seen. [D&E] curcumin concurrently with MSG and
MSG and SY groups) respectively: few spermatogonia are seen with mild
MSG
2108
FOOD ADDITIVES AND CURCUMIN
DISCUSSION
Despite the current practice all over the world to
enhance the flavor and taste of foodstuffs by means of
food additives, their increased use could greatly affect
human health. The outcomes of our study revealed that rats
treated with MSG and SY showed a statistically significant
rise in their mean body weight compared with controls.
These results agreed with other studies[1,31]. Increased
body weight in MSG-treated rats could be attributed to the
palatability of food in addition to salt and water retention
as a result of increased plasma cortisol levels. Moreover,
the hypothalamus does not have an impermeable blood-
brain barrier. As a result, free glutamic acid from food
could easily reach the hypothalamus, injuring and finally
killing its neurons[32]. This leads to impaired leptin and
insulin signaling in this region where leptin acts as an
appetite-suppressing hormone that controls appetite and
body weight[33].
In the present study, a significant increment in protein
carbonyl (PC) levels was observed in MSG- and SY-
treated rats compared to other groups. Sharma et al.[34]
found increased PC levels in MSG-treated rats. Previous
studies suggested that elevated glutamate levels lead to
protein oxidation, oxidative stress, production of reactive
oxygen species, and mitochondrial dysfunction. Increased
PC levels in SY-treated rats are in line with Qujeq et al.[35]
where protein oxidation occurred as a direct consequence
of an attack by free radicals.
The present work revealed that MSG and SY
consumption led to a significant increase in serum lipid
profile. On the contrary, HDL-cholesterol showed a
significant decrease in the MSG group only compared
to other groups. Similar results were recorded by Helal
et al.[2] and Tawfek et al.[18]. Previous studies have proved
that ROS could react with thiol moieties producing sulfur
oxidant molecules which might attenuate insulin receptor
signaling and inhibit cellular uptake of the triglycerides
from blood with a subsequent increase in their levels[35]. In
addition, MSG was believed to stimulate lipid catabolism
via the up-regulation of oxidative genes especially those
hydroxylase (CYP7A1)[36]. Furthermore, these changes
might be attributed to the mobilization of free fatty
acids from adipose tissue to the bloodstream resulting in
increased acetyl CoA levels and an increase in cholesterol
synthesis or due to lipid peroxidation of cell membranes[37].
The SY showed a less toxic effect on lipid profile which
might be due to its minimal direct or indirect action on
lipid peroxidation and its potent antioxidant mechanism[18].
In the present study, the histopathological findings in
the liver, kidney, and testis were more prominent in MSG
than in SY. Similar findings were also observed by El-Borm
et al.[38]. Monosodium glutamate and SY caused degenerative
changes in hepatocytes in the form of fatty degeneration
with vacuolations, necrosis, and mononuclear cellular
infiltration. Vacuolation of hepatocytes was explained
by Cheville[39] who reported that the presence of well-
circumscribed vacuoles is characteristic of fatty changes in
hepatocytes which may occur due to the collection of the
toxic substances to prevent them from interfering with the
biological activities of these cells. Other authors suggested
that vacuolation of hepatocytes as ballooning degeneration
might be a kind of cellular defensive mechanism against
toxic substances[40]. Hepatocyte degeneration of the present
study was confirmed by a significant increase in caspase
3 positive reaction in Monosodium glutamate and SY
groups. Walker and Lupien[41] explained that apoptosis
and necrosis are caused by the accumulation of glutamine
in hepatocytes resulting in degenerative changes and
necrosis. Monosodium glutamate stimulates apoptosis
through the formation of reactive oxygen species (ROS)
which are associated with oxidative stress[42]. In the current
study proliferation of bile ductules lined by vesicular nuclei
characteristic of oval cells in rats could be detected. This
was in accordance with the results of Schaff and Nagy[43].
They reported that hepatocyte necrosis and degeneration
led to a proliferation of the oval cells (stem cells) lining the
bile ductules in an attempt to repair the degenerated cells.
The histopathological findings were concomitantly
associated with aberrations in biochemical indices. The
daily administration of Monosodium glutamate and SY
caused a significant increase in serum ALT, AST, GGT,
and total bilirubin concentrations when compared to the
control rats. These results seemingly agree with Tawfek
et al.,[18] and AL-Sharkawy et al.[44] who attributed this to
hepatocellular impairment and liver dysfunction which
occurred secondary to increased plasma membrane
permeability and cellular necrosis, with subsequent
release of intracellular enzymes into the bloodstream.
Monosodium glutamate dissociates easily releasing free
glutamate followed by the production of ammonium ion
(NH4+) that is mostly toxic unless detoxified via the urea
cycle in the liver[2]. In addition, free radical production by
food additives reacts with fatty acids of the cell membrane
leading to mitochondrial dysfunction, destruction of plasma
membranes, and finally enzyme leakage[45]. Furthermore,
the increased activity of GGT in Monosodium glutamate-
treated animals may be due to liver injury resulting from
Monosodium glutamate-induced oxidative stress[17]. The
drop in albumin levels observed in Monosodium glutamate-
treated groups could be attributed to the inhibitory effect
of Monosodium glutamate on the biosynthesis of albumin
or due to inhibiting the oxidative phosphorylation process.
This in turn denoted the liver’s inability to perform its
functions[46].
In the kidney, Monosodium glutamate and SY affect
the structure and function causing atrophy of glomeruli
and tubular degenerative changes. The proliferation of
extraglomerular mesangial cells could be in the present
work. Some authors stated that extraglomerular mesangial
cells act as reserve cells that proliferate in response to
glomerular atrophy to replace its cells. Other investigators
declared that extraglomerular mesangial cells are stem cells
2109
Abdelhamid et. al.,
for podocytes[47]. Accumulation of collagen fibers; both
inside the glomeruli and in the interstitium of the kidney
was detected in the food additive-treated groups of the
present study. Some authors declared that Mesangial cells
are triggered under pathologic circumstances, resulting in
hyperproliferation and an abundance of extracellular matrix
(ECM). Also decreased degradation of the mesangial matrix
by metalloproteinases occurred. Additionally, mesangial
cells secrete many inflammatory cytokines, adhesion
molecules, chemokines, and enzymes that all contribute to
the development of renal glomerular fibrosis. Interstitial
fibrosis was explained by the Epithelial-mesenchymal
transition of degenerated tubular cells (EMT) in which
the epithelial cells transformed into fibroblasts-like cells
features (characterized by the generation of interstitial
collagens such as type I and type III)[47].
In the same context, El-Borm et al.[38] found degeneration,
inflammation, areas of necrosis, vacuolation of renal tubular
cells, and glomerular atrophy with Monosodium glutamate.
Mahmoud[48] verified that the administration of SY caused
destructive changes and necrosis in the liver, kidney, spleen,
and brain cell layers of experimental animals. Sharma[7]
suggested that oxidative stress is the cause of kidney damage
caused by Monosodium glutamate with the formation of
ROS which is considered a major cause of nephrotoxic
effects leading to cellular and functional damage. Also,
El-Borm et al.[38] stated that regulated cell death of renal
tubules results in membrane-bounded vesicle and crystal
nucleation (renal stone). Monosodium glutamate changes
renal antioxidant system markers; and reduces activities of
superoxide dismutase, catalase, glutathione-S-transferase,
and glutathione (GSH) in the kidney. Other authors noticed
patchy tubular necrosis and interstitial infiltrations in rats
fed with Monosodium glutamate-contaminated food[38]. In
the present study, a significant decrease in the mean optical
density of BCL2-positive kidney cells was noticed in
Monosodium glutamate and SY groups. This might indicate
increased cell death because of Monosodium glutamate
and SY administration. Khayyat et al.[49] reported that
BCL2 is an apoptosis regulatory protein that has an anti-
apoptotic function, promotes cell cycling, and increases cell
resistance to apoptosis.
These structural changes in the kidney affected its
function as confirmed by the results of the current kidney
function tests where administration of Monosodium
glutamate and SY caused a significant increase in serum
urea, creatinine, and uric acid concentrations, compared
to control groups. Some previous studies reported the
same results[2,13,45]. Blood urea is the principal end-
product of protein catabolism and is considered a good
indicator of kidney functional state; however, elevated
serum creatinine concentrations could have a more
prognostic significance than other nitrogenous substances
in renal diseases[18]. Impaired renal functions might occur
following the administration of Monosodium glutamate
and SY either because of their metabolites on renal
tissues or secondary to oxidative stress. This resulted in
interference with creatinine metabolism causing increased
synthesis and leading to the impaired functional capacity
of tubular excretion[50]. It is suggested that hyperuricemia
is accompanied by oxidative stress where xanthine oxidase
catalyzes the oxidation of hypoxanthine/xanthine to uric
acid with a generation of superoxide radicals[51]. On the
contrary, Tawfik and Al-Badr[17] recorded decreased urea
concentrations in the Monosodium glutamate group
compared to controls attributing this to the impaired urea
cycle by food additives with a subsequent decrease in urea
production.
Regarding reproductive function, this work
demonstrated a significant reduction in serum testosterone
levels in the Monosodium glutamate- and SY-treated
groups with a significant decrease in the Monosodium
glutamate group compared to SY. This agreed with Sakr
and Badawy[16] who reported that this might result from a
neuronal loss in the hypothalamus with disruption of the
hypothalamic-pituitary-testis regulatory axis that controls
the production of testosterone by Leydig cells. In addition,
oxidative stress inhibits the sensitivity of gonadotrophic
cells to gonadotropin-releasing hormone and prevents
gonadotropin secretion. Since testosterone and LH are
essential for normal testis function and spermatogenesis,
therefore, their decrease can adversely affect the
reproductive ability of the affected animals[2].
These biochemical analyses were confirmed by the
current histological and immunohistochemical results. The
rats exposed to Monosodium glutamate and SY showed a
widening in the interstitial spaces between seminiferous
tubules with homogenous acidophilic exudates and
congested blood vessels. Germinal epithelium showed
degenerated cells with, vacuolation, exfoliation, and large
areas of cell loss which may be signs of testicular toxicity.
These results were confirmed by a significant decrease
in immunoreactivity for PCNA. Sunset yellow showed
a slight decrease in PCNA compared to monosodium
glutamate with the presence of PCNA-positive Leydig
cells. An increase in the reactivity of PCNA with sunset
yellow might be due to a lack of oxidative stress. Oxidative
stress results in the withdrawal of cells from the cell cycle.
This was in consideration by Das and Ghosh[52] who
noticed that mice exposed to Monosodium glutamate
exhibited slight to moderate damage to seminiferous
tubules, including vacuolization of spermatogonia and loss
of late spermatids. This could also be explained by Storto
et al.[53] who reported that excessive glutamate dissociated
from Monosodium glutamate may hyper-activate the m-Glu
receptors present in Sertoli cells resulting in pathological
changes in the tubular lumen. Kianifard[54] reported that rats
treated with Monosodium glutamate showed atrophy of
seminiferous tubules and depletion of germinal epithelium
accompanied by derangement of spermatogenic cells. He
added that Monosodium glutamate led to the alteration
of cellular junction between the spermatogenic cells.
A significant decrease in the thickness of the germinal
epithelium was noticed in the Monosodium glutamate
2110
FOOD ADDITIVES AND CURCUMIN
group. Alalwani[55] added that the testis is considered a
target organ for Monosodium glutamate. The neurotoxins
released from Monosodium glutamate could affect the
function of the hypothalamus-pituitary-gonadal system.
The congested blood vessels observed in the current
study in Monosodium glutamate and SY groups were
explained by Balasubramanian et al.[56] who attributed them
to the inhibition of prostaglandins synthesis since these
compounds are known to be involved in the regulation of
blood flow.
Increased collagen fibers were noticed in the current
study in the liver, kidney, and testis in Monosodium
glutamate and SY groups. This was confirmed by the
current statistical analysis. Sarhan[57] suggested that the
cause of this fibrosis is due to oxidative stress and the
formation of ROS which can induce the transformation of
fibroblasts to myofibroblasts and increase the deposition
of collagen fibers in liver, kidney, and testicular tissues.
While Ibrahim et al.[58] attributed the cause of fibrosis to the
diminished production of glutathione peroxidase.
In the present work, the groups that received daily
Monosodium glutamate and SY had a depletion of PAS-
positive glycogen content in the liver tissues associated with
a significant decrease in glycogen content in hepatocytes,
this was in accordance with Dorreia et al.[59]. Mustafa et
al.[60] suggested that Monosodium glutamate stimulates
glycogenolysis and gluconeogenesis in the liver leading to
a reduction in the glycogen content, hyperglycemia, and a
decrease in insulin sensitivity. In the Kidney, the basement
membranes appeared thick with a significant increase
compared to the control group, and the brush borders
of some renal corpuscles were disturbed. There was an
apparent increase in the mesangial cells after exposure to
SY. Zhao[47] mentioned that intraglomerular mesangial cells,
which make up roughly 30–40% of all glomerular cells,
are the primary cellular components of the PAS-positive
glomerular mesangium. Also, in the testis, there was
thickened basal lamina, absent acrosomal cap reaction, and
absent glycocalyx reaction in Monosodium glutamate and
SY groups with a significant increase in basal membrane
thickness compared to the control group. This finding goes
in agreement with El-Borm et al.[38]. Mahmoud[48] attributed
the increased thickness of the basement membranes to the
hyperglycemia caused by Monosodium glutamate that
enhanced type IV collagen production which is the main
component of the basement membranes.
Our study revealed that the addition of curcumin
to food additives showed decreased body weight gain
compared with the positive treated groups. Teich
et al.[61] reported similar results, supposing that curcumin
administration leads to significant improvement in insulin
sensitivity, glucose tolerance, and body fat content with
suppression of glucocorticoid action. Curcumin caused
a significant decrease in PC levels compared to groups
treated with food additives alone. Sakr and Badawy[16]
considered curcumin as a powerful antioxidant that
inhibited lipid peroxidation by free radical scavenging
activity and stimulating endogenous antioxidant enzymes
like glutathione peroxidase, glutathione-s-transferase,
SOD, and CAT.
Concomitant administration of curcumin with
Monosodium glutamate and SY improved the most
hazardous effects that occurred in the kidney. A similar
finding was also reported by other authors[34]. In our study,
curcumin has restored alterations in lipid profile resulting
from Monosodium glutamate and SY which is consistent
with Ali et al.[62] indicating that curcumin prevents
increases in serum cholesterol concentrations by inhibiting
dietary cholesterol absorption. Curcumin reduced liver
enzymes to normal levels and restored albumin levels
in the Monosodium glutamate-treated group. A similar
observation was also reported by El-Borm[38]. Adewale
et al.[63] reported that most hepatocytes appeared normal
after treatment with curcumin. The cytoprotective effect of
curcumin observed in the current study could be explained
by its ability to inhibit the oxidative stress induced by food
additives by decreasing lipid peroxidation and increasing
antioxidant capacity[16]. Curcumin reduces free radical-
induced tissue damage, prevents lipid peroxidation,
upregulates biosynthesis of various cytoprotective
and antioxidant proteins, and inhibits inflammatory
cytokines[64].
CONCLUSION
Monosodium glutamate and SY could adversely induce
different structural and biochemical changes in the liver,
kidney, and testis of adult male albino rats. Monosodium
glutamate induced oxidative stress and had more toxic
effects in comparison to SY. Supplementation with
curcumin extract could successfully ameliorate their toxic
effects through its antioxidant action.
FUNDING
There has been no significant financial support for this
work that could have influenced its outcome.
CONFLICT OF INTERESTS
There are no conflicts of interest.
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