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Effects of sodium benzoate, a commonly used food preservative, on learning,

memory, and oxidative stress in brain of mice

Article  in  Journal of Biochemical and Molecular Toxicology · December 2017

DOI: 10.1002/jbt.22022

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Received: 12 September 2017 Revised: 17 November 2017 Accepted: 28 November 2017

DOI: 10.1002/jbt.22022

Effects of sodium benzoate, a commonly used food

preservative, on learning, memory, and oxidative stress
in brain of mice
Mohammad Javad Khoshnoud Asma Siavashpour Mojgan Bakhshizadeh
Marzieh Rashedinia

Department of Pharmacology and Toxicology,

Faculty of Pharmacy, Shiraz University of Medi- Abstract
cal Sciences, Shiraz, Iran Sodium benzoate (SB) is a widely used preservative and antimicrobial substance in many foods and
Correspondence soft drinks. However, this compound is generally recognized as safe food additives, but evidence
Marzieh Rashedinia
has suggested that a high intake of SB may link to attention deficit-hyperactivity disorder in chil-
Email: Rashedinia@sums.ac.ir
dren. Present study investigate the effects of oral administration of different concentrations of SB
Funding information
Shiraz University of Medical Sciences, (0.56, 1.125, and 2.25 mg/mL) for 4 weeks, on the learning and memory performance tests, and
Grant/Award Number: 94-01-103-11070 also the levels of malondialdehyde (MDA), reduced glutathione (GSH), and acetylcholinesterase
activity (AChE) in the mouse brain. The results showed that SB significantly impaired memory and
motor coordination. Moreover, SB decreased reduced GSH and increased the MDA level in the
brain significantly (P < 0.001). However, nonsignificant alteration was observed in the AChE activ-
ity. These findings suggest that short-term consumption of SB can impair memory performance
and increased brain oxidative stress in mice.

KEYWORDS
acetylcholineesterase, glutathione, lipid peroxidation, memory, sodium benzoate

1 INTRODUCTION with attention-deficit hyperactivity disorder (ADHD)-related symp-

Sodium benzoate (SB), the sodium salt of benzoic acid, is a well-
stable and water-soluble food preservative with bacteriostatic and
fungistatic properties.[1,2] It is used in various food products such as
fruit juices, fruit based fillings, pickles, salad dressings, jams, and car-
bonated drinks as well in cosmetics.[3] In medical applications, SB has
been used as therapeutic agents to treat the acute hyper ammonemia
in patients with urea cycle disorders,[4] acute hepatic encephalopathy
and also, multiple sclerosis.[3] FAO/WHO expert committee on food
additives recommends acceptable daily intake levels of SB as 5 mg/kg-
bw.[5] However, the harmlessness of food additives are tested and this
compound is generally recognized as safe,[6] but excessive intake of
these preservatives might be potentially harmful to the consumers.
Studies have suggested that excessive use of SB induced changes in
serum clinical parameters, showing hepatocellular damage,[7] because
in the human body, SB is conjugated with glycine in the liver and
excreted as hippuric acid in the kidney.[6] Moreover, allergic contact
dermatitis, convulsion, hives, asthma, diarrhea, and intestinal hemor-
rhage have been seen in rats.[8,9] Also, it has been reported that SB
is able to induce neurotoxicity, nephrotoxicity, and teratogenicities
during early embryogenesis of zebrafish larvae.[10] There are increas-
ing evidence suggesting that a high intake of SB would be associated
toms in young children.[11–13] However, evidence from some experi-
mental studies have supported the benefits of SB as a metabolite of cin-
namon, a widely used food spice and flavoring, in increasing the levels
of neurotrophic factors such as brain-derived neurotrophic factor and
neurotrophin-3.[14–16] This was supported by in vivo studies in animal
model of Alzheimer's disease (AD), which demonstrated that SB pro-
tects memory and learning by attenuation oxidative stress in the hip-
pocampus of 5XFAD transgenic mice by reducing homocysteine level
and increasing level of reduced glutathione (GSH).[17] Furthermore, Lin
et al.[16] demonstrated that 24 weeks treatment by SB improved cogni-
tive and overall functions in patients with early-phase AD without evi-
dent side effects.
Oxidative stress and free radical generation have been implicated
in the pathogenesis of several brain disorders such as AD, Parkinson's
disease, multiple sclerosis, schizophrenia, and autism.[18,19] It has also
been suggested that depletion of GSH, the main CNS antioxidant, as a
result of increased oxidative stress, play important role in the decline of
cognitive functions and disruption of short-term spatial memory.[19,20]
According to the mentioned studies, effects of SB on health, espe-
cially on the memory and nervous system, are quite controversial.
Previously, a few studies have been conducted to study any relation-
ship between SB consumption and cognitive function and also brain

J Biochem Mol Toxicol. 2017;e22022. wileyonlinelibrary.com/journal/jbt 

c 2017 Wiley Periodicals, Inc. 1 of 7
https://doi.org/10.1002/jbt.22022
2 of 7
oxidative stress indices. The purpose of this study was to evaluate the
effect of short-term SB administration on memory, learning, and motor
coordination in mice. Also, the oxidative stress indices and acetyl-
cholinesterase (AChE) activity were determined in the brain tissue of
treated mice.
2 MATERIALS AND METHODS
2.1 Chemicals
Sodium benzoate, GSH, thiobarbituric acid (TBA), 5,5′ -dithiobis-2-
nitrobenzoic acid (DTNB), and thiocholin were purchased from Sigma–
Aldrich (St. Louis, MO). All other chemicals, which are products of
Sigma Chemical Company (St Louis, MO), were of analytical grade and
were prepared in the laboratory in double glass distilled water.
2.2 Animals
Swiss male Albino mice (25–30 g) were obtained from the Center of
Comparative and Experimental Medicine (Shiraz University of Medi-
cal Sciences, Shiraz, Iran) and held in our laboratory for at least 1 week
prior to the experiment. The animals were fed a standard laboratory
diet and water ad libitum and housed in a temperature (22 ± 2◦ C) with
a 12 h light–dark cycle, and a relative humidity of 50%–55%. All exper-
iments were carried out in accordance with institution guidelines for
Laboratory Animal Care and Use, and were approved by the local Uni-
versity Animal Care and Use Committee, Shiraz University of Medical
Sciences, Shiraz, Iran (94-01-103-11070).
2.3 Experimental design
Animals were randomly divided into five groups (n = 8). Control mice
received regular tap water and treated mice received different con-
centration of SB in the drinking water (0.56, 1.125, and 2.25 mg/mL
day) for 4 weeks. Water consumption as well as body weight was
recorded.
Positive control group was administered with 1 mg/kg of diazepam
(DZP) before behavior tests. At the end of 4 weeks, the behavioral
tests were performed in experimental groups as described below. Then
the animals were sacrificed by decapitation. Their blood was collected
and the serum was isolated and stored in a −20◦ C freezer. Also, brains
were rapidly removed, washed in a cold saline solution, and weighted,
then snap-frozen in liquid nitrogen and stored at −80◦ C for the time of
assays.
2.4 Behavioral tests
The rotarod, shuttle-box, and step-down tests were performed to eval-
uate muscle coordination, learning, and memory.
2.4.1 Rotarod test
Motor coordination of mice was assessed by rotarod test. The rotarod
apparatus consisted of a rotating rod with a diameter of 4 cm and rough
KHOSHNOUD ET AL .
surface. The rod was placed at a height of 20 cm from the base, divided
into five equal sections separated by chambers. It was controlled by the
speed of rpm. Below the rolling rod, a base platform had a control time
recorder when the mice fell from the rod. Learning trial was performed
for each animal and allowed to climb or move along the rod before the
real test. The balance and sensory motor coordination of the animals
was assessed on the basis of the time of falls from the rod in cut-off
time 60 s at 10 rpm. The performances were repeated three times for
each animal with an interval of 15 min between each trial.[21]
2.4.2 Shuttle box test
The effects of SB on learning and memory function were evaluated
using a step-through passive-avoidance test according to the method
previously described by Jarvik and Kopp.[22] The apparatus consisted
of a two-compartment acrylic box with a grid floor. The lighted com-
partment was separated from the darkened compartment by a guillo-
tine door. In the training test, the animals were placed in the lighted
compartment, while the sliding door was opened; as soon as the mouse
entered the dark compartment, the door was closed and the animal
received a punishing electrical foot-shock (1 mA for 1 s). The latency
time for entering the dark compartment were measured and the cut-
off latency time was 60 s. The retention test was performed 24 h after
the training using the same pattern, but without electric shock, and the
step-through latency (STL) for mice to enter the dark compartment
was considered. The maximum entry latency allowed in the retention
sessions was 300 s.
2.4.3 Step-down test
The inhibitory avoidance step-down apparatus was a (30 × 30 × 40 cm
high) plastic box, with a wooden platform (4 × 4 × 4 cm) placed at the
center of the floor of training box, the floor of which consisted of par-
allel 0.3 cm stainless steel bars spaced 1 cm apart. Before the train-
ing session, each animal was permitted to move 20 min freely through-
out the chamber for adaptation. In the learning test, the animals were
placed on the platform, immediately after stepping down on the grid,
they received electric foot shock (1 mA for 1 s). After 24 h, retention
test session was carried out again, except without any shock to the ani-
mals. Step-down latency was used as a measure of memory retention.
An upper cut-off latency time of 300 s was considered.[23]
2.5 Determination of reduced GSH
Level of brain reduced GSH was measured using the method previously
described.[24] Briefly, brain tissues were homogenized in cold phos-
phate buffer (0.1 M, pH = 7.4) and also, total protein concentrations
were determined. Tissue homogenates (0.5 mL) was mixed with equal
amount of trichloroacetic acid (TCA, 10%). After vortex and centrifu-
gation, 0.5 mL of supernatants was mixed with reaction buffer con-
taining 0.5 mL of 0.01 M DTNB and 3 mL of phosphate buffer (0.3 M,
pH 8.4). Absorbance was measured at 412 nm within 10 min using
an automated plate reader (ELX800 ELISA Reader; BioTek, Winooski,
Vermont, USA). Levels of GSH were reported as 𝜇mol/mg protein.
KHOSHNOUD ET AL . 3 of 7

2.6 Determination of lipid peroxidation TA B L E 1 Mean body weight and daily intake of water in SB treated
group
Lipid peroxidation was determined by measuring the levels of malondi-
First Day Last Day Water
aldehyde (MDA) in the brain tissues.[25] In brief, 1 mL of homogenized Body Weight Body Weight Intake /
brain tissues were mixed with 1 mL of 20% TCA, 0.5 mL of 0.5 N HCl, Groups (g)a (g)a day (mL)a
and 1 mL of 0.6% TBA, the samples were then heated in boiling water Control 24.81 ± 1.04 30.51 ± 3.18 6.13 ± 2.8
bath for 45 min. After cooling the samples to room temperature, SB 0.56 mg/mL 24.55 ± 2.79 31.1 ± 3.15 5.95 ± 2.5
they were centrifuged for 10 min at 6000 × g. The thiobarbituric SB 1.25 mg/mL 25.92 ± 3.8 31.45 ± 4.39 6.5 ± 2.7
acid reactive substances (TBARS) were determined by measuring SB 2.25 mg/mL 25.93 ± 3.34 27.58 ± 2.85 6.9 ± 2.6
absorbance at a wavelength of 540 nm spectrophotometer (S-2150; a
Data are expressed as means ± S.E.M.
UNICO, Shanghai, China). Levels of MDA in samples were reported as
nmol/mg protein.
the mean of body weight at the end of the study showed no significant
differences among the groups.
2.7 Determination of brain and serum AChE activity
Brain and serum cholinergic function was assessed by AChE activity.
3.2 Effect of SB on learning and memory
The quantitative measurement of AChE activity was determined 3.2.1 Step-down test
according to the colorimetric method of Ellman et al.[26] The assay
Statistical analysis revealed that treatment with all doses of SB
mixture contained 50 𝜇L of brain tissue supernatant or diluted serum,
(0.56, 1.125, and 2.25 mg/mL) and DZP significantly (P < 0.001)
140 𝜇L of 0.01 M phosphate buffer (pH 8), and 5 𝜇L of 1 mM DTNB
decreased the latency to step down compared with the control group
(Ellman reagent) added in 96-well microplate. After 5 min incubation
(Figure 1).
at 25◦ C, 2 𝜇L of 0.05 mM acetylthiocholine iodide was added as the
substrate. The change in absorbance was measured at 412 nm for 3.2.2 Shuttle-box test
3 min by automated plate reader (ELX800 ELISA Reader; BioTek,
Learning and memory deficits were observed in a group of mice treated
Winooski, Vermont, USA). All the samples were run in triplicate and
with high dose of SB (2.25 mg/mL). The STL was decreased significantly
results were calculated using molar extinction coefficient of chro-
by administration 2.25 mg/mL of SB for 4 weeks (P < 0.01) as compared
mophore (𝜀 = 1.36 × 104 M−1 cm−1 ) and the enzyme activity was
with the control group. Also, DZP (1 mg/kg) significantly decreased STL
expressed as U/mg protein.
(P < 0.5), indicating its amnesic effect (Figure 2). There was no signifi-
cant difference in STL between 0.56 and 1.125 mg/mL of SB and con-
2.8 Protein assay trol groups. Also, the same results has shown among 0.56, 1.125, and
2.25 mg/mL SB groups and DZP group (Figure 1).
Total protein concentration in tissues were determined using a pro-
tein assay kit (Bio-Rad #500-0002, BIORAD Laboratories, Hercules,
3.2.3 Rotarod test
California, USA).
All groups of SB (0.56, 1.125, and 2.25 mg/mL) showed a significant
impairment of the rotarod performance (P < 0.001) by decreasing the
2.9 Statistical analysis time on rode in compared with control group (Figure 2).
Statistical analysis of data was carried out using SPSS 22.0 software.
Results are expressed as mean ± S.E.M. of eight experiments. One-way 3.3 Effect of SB on brain reduced GSH
analysis of variance (ANOVA) and Dunnet multiple range test were
The administration of SB at the doses of 0.56, 1.125, and 2.25 mg/mL in
used to test the difference between the groups. P < 0.05 was consid-
the drinking water showed a significant decrease in the brain reduced
ered as statistically significant difference in all experiments.
GSH level compared with the control group (P < 0.001) (Figure 3).

3.4 Effect of SB on brain MDA

3 RESULTS
The significant increase in the brain MDA level observed after the
administration of SB at the doses of 0.56, 1.125, and 2.25 mg/mL com-
3.1 Effect of SB on weight and water consumption
pared with the control group (P < 0.001) (Figure 4).
The FDA-permitted concentration of SB in food is 0.1% by weight.[5]
In this study, the concentration of SB in water was 0.225%–0.56%. The
3.5 Effect of SB on the serum and brain AChE
water consumption for all groups was measured every 2 days and the
activity
body weights determined weekly are presented in Table 1. Regarding
the volume of water consumption, the daily intake of SB approximately The results obtained for AChE activity in serum and brain tissue are
were 150, 300, and 600 mg/kg, respectively. As can be observed, the presented in Figure 5. No significant differences in AChE activity were
treatment with SB had no effects on the water consumption and also, observed in all groups of SB when compared with the control group.
4 of 7 KHOSHNOUD ET AL .

F I G U R E 1 Effects of sodium benzoate (SB) on latency of time spent on the platform in step-down test and the average time on step-through
latency in shuttle box test. The groups of mice received different concentration of SB in the drinking water (0.56, 1.125, 2.25 mg/mL day). Diazepam
administered as a positive control. Data are expressed as means ± S.E.M. (n = 8). SB, sodium benzoate; DZP, diazepam. * P < 0.05, ** P < 0.01, and
*** P < 0.001 were considered to be significant compared with the control group

F I G U R E 2 Effects of sodium benzoate (SB) on time on rode in the rotarod test. The groups of mice received different concentration of SB in the
drinking water (0.56, 1.125, 2.25 mg/mL day). Diazepam administered as a positive control. Data are expressed as means ± S.E.M. (n = 8). SB, sodium
benzoate; DZP, diazepam. * P < 0.05, ** P < 0.01, *** P < 0.001 were considered to be significant compared with the control group

4 DISCUSSION Our results showed that exposure to SB (approximately 130–

Benzoic acid and SB are extensively used preservatives in dietary food
products, but chronic exposure in vivo studies to evaluate their effects
are limited to report about reduced growth and feed intake in mice and
rats.[5] Furthermore, short time exposure caused some harmful effects
on rat liver and kidney functions,[7] anxiety, and motor impairment in
rats.[13]
Previous studies have suggested that SB consumption may con-
tribute to ADHD symptoms and childhood hyperactivity.[27,28]
550 mg/kg/day) cause coordination deficit probably for the reason that
cerebellar and striatal dysfunction.[29]
Moreover, body injuries and lesion on the back and tail of mice
have been seen in the all groups of SB treated compare with
the control, and they may be a result of aggressive and fighting
behavior, in agreement with the previous reports by Noorafshan
et al.[13]
Although previous studies have demonstrated neuroprotective
effects of SB in AD and Schizophrenia patients or AD animal
KHOSHNOUD ET AL . 5 of 7

F I G U R E 3 Effects of sodium benzoate (SB) on the brain tissue reduced glutathione (GSH: 𝜇mol/mg protein). The groups of mice received different
concentration of SB in the drinking water (0.56, 1.125, 2.25 mg/mL day). Diazepam administered as a positive control. Data are expressed as means
± S.E.M. (n = 8). SB, sodium benzoate; DZP, diazepam. * P < 0.05, ** P < 0.01, *** P < 0.001 were considered to be significant compared with the control
group

F I G U R E 4 Effects of sodium benzoate (SB) on the brain tissue levels of malondialdehyde (MDA: nmol/mg protein). The groups of mice received
different concentration of SB in the drinking water (0.56, 1.125, 2.25 mg/mL day). Diazepam administered as a positive control. Data are expressed
as means ± S.E.M. (n = 8). SB, sodium benzoate; DZP, diazepam. * P < 0.05, ** P < 0.01, *** P < 0.001) were considered to be significant compared with
the control group

models,[16,17,30] but in this study, the toxic effects of SB on learning
and memory were found, which was previously not reported in animals.
The important role of oxidative stress in the pathogenesis of a range
of neurodegenerative diseases is established.[31] Our study showed
MDA levels were increased and GSH levels were decreased in the mice
brain, but limited studies demonstrated opposing results in the disor-
der animal models. Modi et al. observed that both cinnamon and its
metabolite SB inhibited oxidative stress and improved hippocampal
GSH levels and memory performance in 5XFAD transgenic mice as an
antioxidant.[4,14,17]
Our data showed that brain GSH content decreased in DZP group
as compared with the control group, but MDA level did not change sig-
nificantly. Previous study also showed that acute DZP administration
induced oxidative imbalance in different brain regions such as cerebel-
lum, hippocampus, and cerebral cortex.[32,33] However, DZP reduced
the TBARS formation in the whole brain. They suggested that varia-
tion in the antioxidant profile could be due to differential distribution
of prooxidants, antioxidants, and polyunsaturated fatty acids in brain
area.[33]
Several clinical trials have shown that administration of SB sig-
nificantly improved symptoms and neurocognition in patients with
early-phase AD or chronic schizophrenia.[16,30,34] It is believed that SB
is a D-amino acids oxidase inhibitor.[16] D-Amino acids are the neu-
rotransmitters for the co-agonist site of the N-methyl-D-aspartate
6 of 7 KHOSHNOUD ET AL .

F I G U R E 5 Effects of sodium benzoate (SB) on the brain (A) and serum (B) acetylcholinesterase activity. The groups of mice received different
concentration of SB in the drinking water (0.56, 1.125, 2.25 mg/mL day). Diazepam administered as a positive control. Data are expressed as means
± S.E.M. (n = 8). SB, sodium benzoate; DZP, diazepam. * P < 0.05, ** P < 0.01, *** P < 0.001 were considered to be significant compared with the control
group

receptor (NMDAR).[35,36] Although SB as a D-amino acids oxidase
inhibitor has beneficial neuroprotective effects in pathological condi-
tions, but probably chronic intake of SB in the normal condition can be
neurotoxic. Previous studies indicated that the activation of NMDARs
can damage the cellular macromolecules, including lipids, DNA, and
proteins by inducing oxidative stress.[37,38] We suggested that SB may
produce ROS by increasing the activation of NMDAR in the normal
brain. But in the pathological condition, it may optimize NMDAR acti-
vation by changing the level of excitatory amino acids for synaptic
plasticity.[16,39]
Level of GSH play an important role against SB-induced oxidative
stress. Moreover, the brain GSH depletion and oxidative stress have a
potential role in cognitive impairment in psychiatric illnesses.[19,20,40]
Acetylcholine has a fundamental role in learning, memory, and cor-
tical organization of movement and for that reason, the alterations in
activity of AChE lead to cognitive deficits.[41,42]
Although high dose of SB intake showed learning and
memory deficits in the mice behavioral tests, but it has not
shown any effect on the AChE activity in the serum and brain
tissue.
In conclusion, harmful chronic exposure to food additives
like as SB, particularly consumed by the children with a sen-
sitive nervous system, may lead to neurological disorders.
Therefore, it has been suggested that further investigations are
required to find the dual neuroprotective–neurotoxic mechanisms
of SB.
KHOSHNOUD ET AL .
ACKNOWLEDGMENTS
This investigation was extracted from the thesis written by Mojgan
Bakhshizadeh and financially supported by the Vice Chancellor of
Research Affairs of Shiraz University of Medical Sciences grant (#94-
01-103-11070).
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
ORCID
Marzieh Rashedinia http://orcid.org/0000-0001-8395-2944
REFERENCES
[1] M. Pongsavee, BioMed Res. Int. 2015, 2015.
[2] S.C.o.C. Products, Benzoic Acid and Sodium Benzoate, ec.europa.eu/
health/ph_risk/committees/04_sccp/docs/sccp_o_015.pdf, 2005.
[3] A. Yadav, A. Kumar, M. Das, A. Tripathi, Food Chem. Toxicol. 2016, 88,
40.
[4] S. Brahmachari, A. Jana, K. Pahan, J. Immunol. 2009, 183, 5917.
[5] B. Nair, Int. J. Toxicol. 2001, 20, 23.
[6] B. S. Lennerz, S. B. Vafai, N. F. Delaney, C. B. Clish, A. A. Deik, K. A.
Pierce, D. S. Ludwig, V. K. Mootha, Mol. Genet. Metab. 2015, 114, 73.
[7] O. I. Oyewole, F. A. Dere, O. E. Okoro, Eur. J. Med. Plants 2012, 2, 11.
[8] A.C. Gören, G. Bilsel, A. Şimşek, M. Bilsel, F. Akçadağ, K. Topal, H.
Ozgen, Food Chem. 2015, 175, 273.
[9] B. Aşçı, Ş. Dinç Zor, Ö. Aksu Dönmez, Int. J. Anal. Chem. 2016, 2016.
[10] H.-J. Tsay, Y.-H. Wang, W.-L. Chen, M.-Y. Huang, Y.-H. Chen, Neurotoxi-
col. Teratol. 2007, 29, 562.
[11] K. Y. Lok, R. S. Chan, V. W. Lee, P. W. Leung, C. Leung, J. Leung, J. Woo, J.
Dev. Behav. Pediatr. 2013, 34, 642.
[12] A. Connolly, A. Hearty, A. Nugent, A. Mckevitt, E. Boylan, A. Flynn, M.
Gibney, Food Addit. Contam. 2010, 27, 447.
[13] A. Noorafshan, M. Erfanizadeh, S. Karbalay-Doust, Neurosciences
2014, 19, 24.
[14] A. Jana, K. K. Modi, A. Roy, J. A. Anderson, R. B. van Breemen, K. Pahan,
J. Neuroimmune Pharmacol. 2013, 8, 739.
[15] S. Khasnavis, K. Pahan, J. Neuroimmune Pharmacol. 2014, 9, 569.
[16] C.-H. Lin, P.-K. Chen, Y.-C. Chang, L.-J. Chuo, Y.-S. Chen, G. E. Tsai, H.-Y.
Lane, Biol. Psychiatry 2014, 75, 678.
[17] K. K. Modi, A. Roy, S. Brahmachari, S. B. Rangasamy, K. Pahan, PLoS One
2015, 10, e0130398.
[18] M. Hu, J. Wang, J. Cai, Y. Wu, X. Wang, Chin. J. Biotechnol. 2008, 24,
1428.
[19] O. Dean, A. I. Bush, M. Berk, D. L. Copolov, M. van den Buuse, Behav.
Brain Res. 2009, 198, 258.
View publication stats
7 of 7
[20] O. Abdel-Salam, N. Salem, M. El-Shamarka, J. Hussein, N. Ahmed, M.
El-Nagar, Eur. Rev. Med. Pharmacol. Sci. 2012, 16, 2092.
[21] N. Galeotti, A. Bartolini, C. Ghelardini, Behav. Brain Res. 2004, 153, 409.
[22] M. Jarvik, R. Kopp, Psychol. Rep. 1967, 21, 221.
[23] M. Jafari-Sabet, M.-A. Khodadadnejad, S. Ghoraba, R. Ataee, Pharma-
col. Biochem. Behav. 2014, 117, 137.
[24] M. Rashedinia, P. Lari, K. Abnous, H. Hosseinzadeh, Toxicol. Appl. Phar-
macol. 2013, 272, 199.
[25] M. Uchiyama, M. Mihara, Anal. Biochem. 1978, 86, 271.
[26] G. L. Ellman, K. D. Courtney, V. Andres, R. M. Featherstone, Biochem.
Pharmacol. 1961, 7, 88.
[27] B. L. Beezhold, C. S. Johnston, K. A. Nochta, J. Atten. Disord. 2014, 18,
236.
[28] N. Kilic, E. Balkan, S. Akgoz, N. Sen, H. Dogruyol, Int. J. Urol. 2006, 13,
105.
[29] H. Shiotsuki, K. Yoshimi, Y. Shimo, M. Funayama, Y. Takamatsu, K. Ikeda,
R. Takahashi, S. Kitazawa, N. Hattori, J. Neurosci. Methods 2010, 189,
180.
[30] H.-Y. Lane, C.-H. Lin, M. F. Green, G. Hellemann, C.-C. Huang, P.-W.
Chen, R. Tun, Y.-C. Chang, G. E. Tsai, JAMA Psychiatry 2013, 70, 1267.
[31] D. Praticò, Trends Pharmacol. Sci. 2008, 29, 609.
[32] G. A. Eger, V. V. Ferreira, C. R. Batista, H. L. Bonde, D. D. Lima, A. F.
Rodrigues, J. G. P. da Cruz, D. D. D. Magro, J. Biochem. Mol. Toxicol. 2016,
30, 506.
[33] S. Musavi, P. Kakkar, Mol. Cell. Biochem. 1998, 178, 41.
[34] Y.-C. Hou, C.-H. Lai, J. Neuropsychiatry Clin. Neurosci. 2013, 25, E07.
[35] G. E. Tsai, P.-Y. Lin, Curr. Pharm. Des. 2010, 16, 522.
[36] L. V. Kalia, S. K. Kalia, M. W. Salter, Lancet Neurology. 2008, 7, 742.
[37] R. C. Reyes, A. M. Brennan, Y. Shen, Y. Baldwin, R. A. Swanson, J. Neu-
rosci. 2012, 32, 12973.
[38] V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O. Medina-
Campos, F. Pérez-Severiano, S. Ali, J. Pedraza-Chaverri, A. Santamaría,
Neuroscience 2005, 135, 463.
[39] M. P. Mattson, Ann. N. Y. Acad. Sci. 2008, 1144, 97.
[40] E. Niedzielska, I. Smaga, M. Gawlik, A. Moniczewski, P. Stankowicz, J.
Pera, M. Filip, Mol. Neurobiol. 2016, 53, 4094.
[41] A. Martorana, Z. Esposito, G. Koch, CNS Neurosci. Ther. 2010, 16, 235.
[42] R. Schmatz, C. M. Mazzanti, R. Spanevello, N. Stefanello, J. Gutier-
res, M. Corrêa, M. M. da Rosa, M. A. Rubin, M. R. C. Schetinger, V. M.
Morsch, Eur. J. Pharmacol. 2009, 610, 42.
How to cite this article: Khoshnoud MJ, Siavashpour A,
Bakhshizadeh M, Rashedinia M. Effects of sodium benzoate,
a commonly used food preservative, on learning, memory
and oxidative stress in brain of mice. J Biochem Mol Toxicol.
2017;e22022. https://doi.org/10.1002/jbt.22022