Content uploaded by Nurhusien Yimer
Author content
All content in this area was uploaded by Nurhusien Yimer on Jun 06, 2025
Content may be subject to copyright.
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2154
Research Article
Abstract | Lead (Pb) is a heavy metal which possesses a long half-life and a distinct negative effect on the bodies of
humans and animals. Lead precipitates in various tissues of the body, especially the central nervous system, which causes
histological structural changes that may persist even after its concentration in the blood reduces. It produces neurotox-
icity related to the deterioration of brain functions. Edible bird’s nest (EBN) is important natural product that has bi-
ological characteristics, such as regenerative effect. e objective of this research was to evaluate EBN’s neuroprotective
role on the cerebral and cerebellar cortexes of lead acetate-exposed adult female rats. irty Sprague Dawley rats were
allocated randomly into five groups, with six rats in each group. e control group (C) received solely distilled water.
Meanwhile, the treatment groups (T0, T1, T2, and T3) received lead acetate (LA) at a dose of 10 mg/kg BW along with
increasing doses of EBN at 0, 30, 60, and 120 mg/kg BW each day, respectively, for five weeks. Behavioural changes were
monitored in the various groups. Blood sample for measurement of redox status markers (thiobarbituric acid reactive
substances(TBARS) and total antioxidant capacity (TAC)) and brain tissue samples for histopathology, were collected
after euthanization. Aggression, loss of appetite and uncoordinated body movement were increased in T0 group and
absent in the T3 group. Rats pre-treated with EBN showed reduced LA -induced alteration in brain histology and
apoptosis attributed to increased TAC and decreased lipid peroxidation (TBARS). ese results suggest that EBN’s
anti-apoptotic, proliferative, and antioxidant properties lessen the neurotoxicity caused by lead acetate.
Keywords | LA, EBN, TAC, TBARS, Cerebellum, Cerebrum
AbdullA A. Albishtue1,3, NurhusieN Yimer1,5*, md Zuki A. ZAkAriA2, Abd WAhid hAroN1, Abdul
sAlAm bAbji4
Edible Bird’s Nest Mitigates Histological Alterations in the Cortexes
of Rats’ Brains Subjected to Lead Toxicity
Received | December 29, 2023; Accepted | August 28, 2024; Published | September 23, 2024
*Correspondence | Nurhusien Yimer, Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Email:
nurdeg2006@gmail.com
Citation | Albishtue AA, Yimer N, Zakaria MZA, Haron AW, Babji AS (2024). Edible bird’s nest mitigates histological alterations in the cortexes of rats’ brains
subjected to lead toxicity. Adv. Anim. Vet. Sci. 12(11): 2154-2164.
DOI | https://dx.doi.org/10.17582/journal.aavs/2024/12.11.2154.2164
ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331
Copyright: 2024 by the authors. Licensee ResearchersLinks Ltd, England, UK.
is article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.
org/licenses/by/4.0/).
1Department of Veterinary Clinical Studies; 2Department of Veterinary Preclinical Sciences, Faculty of Veterinary
Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Anatomy and Histology, Faculty
of Veterinary Medicine, University of Kufa, Najaf, Iraq; 4Innovation Centre for Confectionary Technology (MANIS),
School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia,
Bangi, Selangor, Malaysia; 5Division of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas
Airlangga, Surabaya, Indonesia.
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2155
INTRODUCTION
Lead has an essential role play in the occurrence of in-
sidious hazards and adverse health effects that lead to
disorders and diseases especially in oil producing and de-
veloping regions (Flora et al., 2012). Lead is a multi-organ
toxicant affecting almost every organ/system of the human
and animal body, especially the central nervous system, re-
productive, hepatic, renal, and immune systems (Kali and
Flora., 2005; Otong et al., 2022). After exposure, lead is
mostly deposited in the bones after being primarily retained
in the kidneys and liver at first (Satarug et al., 2002). Age
and hormone production are two examples of conditions
that might trigger the re-release of lead into the general
circulation (Horiguchi et al., 2013). Consequently, lead has
lengthy half-lives, as reported by Järup (2003), Rzymski et
al. (2014), and Liu et al. (2014). Trace quantities of lead are
eliminated through the urine. Lead accumulates in numer-
ous bodily tissues, primarily in the central nervous system
(CNS), from which it is possible that structural changes
will endure even after the blood concentration is reduced
(Sidhu and Nehru, 2004; Ibrahim et al., 2012).
Epidemiological studies have revealed that chronic lead
poisoning in young children can affect their growth and
cause CNS injury, decreased intelligence, shortterm mem-
ory, hearing loss, irreversible brain damage, and mortali-
ty (Cleveland et al., 2008). e high absorption of lead
through the gastrointestinal tract and the permeable blood-
brain barrier makes children more susceptible to lead expo-
sure (Jarup, 2003; Liu et al., 2015; Barkur and Bairy., 2015).
Over the last decades, the prevalence of neurodevelop-
mental and neurodegenerative disorders has dramatical-
ly increased worldwide. A neurodegenerative disease is
caused by the progressive loss of structure or function of
neurons. Additionally, research has indicated that behav-
ioural dysfunctions, cognitive impairment, and neurode-
generation can result from even low-level lead exposure
(Flora et al., 2012; Chen et al., 2022). Increased oxida-
tive stress, alterations of the cholinergic system and glu-
tamate receptor have all been implicated in experimental
investigations demonstrating the neurotoxic effects of lead
(Shukla et al, 2003; Hossain et al., 2016). Previous studies
have documented a correlation between elevated levels of
lead exposure among occupational workers and heightened
production of free radical species, which subsequently re-
sults in oxidative harm and a reduction in the antioxidant
defence mechanism of affected individuals (Kasperczyk et
al., 2005; Emam et al.,2023). Owing to the generation of
free radicals in the tissues, oxidative stress results in lipid
peroxidation (LPO), which is the mechanism by which all
toxic metals, including lead, induce toxicity (Al-Quraishy
et al., 2016). Reactive oxygen species (ROS) impair the an-
tioxidant defence system and cause damage to a variety of
enzymes, membrane-based lipids and proteins at the same
time (Flora et al., 2012; Albishtue et al., 2020a). Antioxi-
dants are recognised for their ability to absorb and restore
damage caused by free radicals. According to the discovery
that lead-induced pathogenesis processes produced free
radicals, it was hypothesised that antioxidant supplementa-
tion would inhibit or reduce the deleterious effects of lead
while enhancing the efficacy of chelating agents (Flora et
al., 2002). In previous studies, EBN provided protection for
vital organs exposed to LA such as pituitary, ovary, uter-
us, liver and kidney (Albishtue et al., 2018b; Albishtue et
al., 2019c; Albishtue et al., 2020a). EBN powder contains
potential peptides with antioxidant property. Until today,
scientific evidence on EBN’s role in maintaining integrity
of histological structures of cerebral and cerebellar cortexes
exposed to lead acetate toxicity has been lacking. e pres-
ent study was therefore undertaken to evaluate changes in
oxidation and micro anatomy of rats’ cerebrum and cerebel-
lum subjected to LA and EBN supplement.
MATERIALS AND METHODS
ebN PrePArAtioN
EBN was acquired from Nest Excel Resources Sdn Bhd.
stored between 25°C -30°C. As the local suppliers speci-
fied, EBN extract was prepared in adherence to Chinese
tradition. A mixer (BUCHI-400, Switzerland) was utilised
to reduce the samples to powder form after they had been
cleansed and dried at room temperature. At 4°C, the ground
EBN extract was housed. 1 g of EBN powder was dissolved
in 100 mL of distilled water to produce EBN solution,
which was then heated in a water bath at 60 °C for 45 min-
utes. Finally, the rats were given doses of the EBN solution
based on their weights after it had cooled to room tem-
perature (Albishtue et al., 2018e; Albishtue et al.,2019d).
PrePArAtioN of leAd AcetAte solutioN
Oxford Lab. Co., India (CAS: 6080-56-4) provided lead
acetate with the chemical formula Pb (C2H3O2)2. Indi-
vidual rats from the treated groups were administered lead
acetate using a gavage tube (China, Straight, 18 Gauge) at a
dose of 10 mg/kg of body weight. e lead acetate solution
was initially produced as a 1% (w/v) solution in distilled
water (Albishtue et al., 2018b; Albishtue et al., 2019c; Al-
bishtue et al., 2020a).
ANimAls ANd exPerimeNtAl desigN
e Animal Resource Center at the Faculty of Veterinary
Medicine, Universiti Putra Malaysia (UPM), provided 30
female Sprague-Dawley rats (aged 12 weeks) for the study.
For a seven-day acclimation phase, the rats were kept togeth-
er. All rats had unlimited access to water and a regular rat
meal (Gold Coin Brand Animal Feed) throughout the study
and were housed in plastic cages that were kept at a constant
temperature of 25°C ± 2°C. According to the institutional
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2156
animal care recommendations and use committee (IACUC)
guidelines, the animal management and handling proce-
dures were carried out using the reference number UPM/
IACUC/AUP- R009/2016) approved on 11 th April 2016.
exPerimeNtAl desigN ANd cliNicAl observAtioN
Following a 7-day period of acclimation, the rats were di-
vided into 5 random groups of 6 animals each, and 10 mg/
kg of LA was given to each group according on Albishtue
et al. (2018e). Rats were divided into five groups: Control
(C) was given distilled water orally. Positive control (T0)
was given LA (10 mg/kg). Treatment 1 (T1), which re-
ceived EBN (30 mg/kg) and LA (10 mg/kg) orally, daily;
Treatment 2 (T2), which received EBN (60 mg/kg) and
LA (10 mg/kg); and treatment 3 (T3), which received
EBN (120 mg/kg) and LA (10 mg/kg). Over the course
of 5 weeks, LA and EBN were each given orally once, dai-
ly. Following a general anesthesia technique that included
the administration of 30 mg ketamine/kg BW and 10 mg
xylazine/kg BW and blood collection by heart puncture ac-
cording to the method of Albishtue et al. (2019d). EBN
has been previously studied and confirmed for its potential
cognitive enhancing effect, including learning and memory
abilities (Xie et al., 2018; Mahaq et al., 2020; Loh et al.,
2022), therefore a group receiving only EBN without lead
acetate was not considered in the study design. Clinical
monitoring of the rats was done every day. However, im-
portant observations, such as aggression, reduced appetite
and balance inability, were summarized at each group and
presented in scores based on the number of rats showing
such signs within a group (Assi et al, 2018). CO2 asphyxia-
tion was used to euthanize rats.
oxidAtive stress biomArker (osb) ANd
ANtioxidANt (Ao) AssAY
Plasma samples were also collected in order to per-
form analyses for AOs such as total AO capacity (TAC)
and OSBs such as thiobarbituric acid reactive substance
(TBARS) which determine marker of lipid peroxidation In
accordance with Schmidt et al. (2014) and Ye w et al. (2014)
e QuantiChromeTM TBARS Assay Kit, DTBA-100,
was utilised to measure the amount of TBARS in order to
determine the level of lipid peroxidation in the plasma.A
commercial kit called the QuantiChromeTM AO Assay Kit
(DTAC-100) was used to assess the TAC. Metmyoglobin
oxidises 2,29-azino-di-3-ethybenzthiazoline sulfonate,
and this process is blocked by non-enzymatic AOs present
in the sample. All the above assay kits were obtained from
Bioassay System, San Francisco Bay Area, USA.
histoPAthologicAl exAmiNAtioN ANd scoriNg
Following the anesthesia-induced rat sacrifice, tissue sam-
ples from the cerebellum and cerebrum were removed and
preserved for 48 hours in 10% neutral buffered formalin.
Using an automated tissue processor (Leica TP1020, Ger-
many), fixed tissue samples were processed via a series of
dehydrations in ethanol. Sample tissues were cut into 4 µm
sections using a microtome (Leica 2045, Germany), im-
mersed in paraffin blocks (Leica EG 1150C, Germany),
and ribbon-like sections were created. To get them nicely
stretched, sections were submerged in a floating water bath
(Triangle Biomedical Science) for 15 minutes. Following
this, glass slides were used to remove the tissues from the
water bath. ese slides were then allowed to dry on a hot
plate (Leica HI 1220) in preparation for histological anal-
ysis using conventional methods of hematoxylin and eosin
(H&E). To enable for section preservation, the slides were
mounted with cover slip using DPX mounting medium.
Stained tissues were inspected using an image analyzer
microscope and light microscopy. For every tissue section,
three microscopic regions of identical size were examined
at different magnifications (20x and 40x). For analysis, sec-
tions were chosen at random using Medical Image Analysis
(Motic Image plus 2.0, China). e samples were examined
under a microscope to check for changes in histomorpholo-
gy. At magnifications of 20x and 40x, the degeneration score
of the cerebral and cerebral cortexes in a given location was
recorded. e severity of the lesion was rated on a scale of 0
to +3 (0, none; 1, mild; <30%); 2, moderate; <60%); and 3,
severe; <60%) (Albishtue et al, 2020a)., the density of gran-
ular cells was graded from 0 to +3 at magnification of 20x.
stAtisticAl ANAlYsis
Graph Pad Prism 6.0 (Graph Pad Software, San Diego,
California) was used to examine all the data, which were
expressed as means (M) ± standard error of mean (SE). e
acquired data were subjected to the Shapiro-Wilk test to
ensure normal distribution. e concentrations of AOs and
OSBs in the sera were compared using a one-way analysis
of variance (ANOVA) and the Tukey multiple comparison
post-hoc test. Using a Kruskal-Wallis (non-parametric)
test, histological lesions in the cerebellum and cerebrum
were compared. A value of p<0.05 was deemed significant.
RESULTS AND DISCUSSIONS
cliNicAl observAtioNs
At 35 days from treatment, it was shown that the T0 and
T1 groups had greater rates of the major clinical obser-
vations that include aggression, appetite loss and inability
to coordinate movement, but the T2 group had a smaller
proportion while the T3 group had none (Table 1).
histomorPhologicAl fiNdiNgs iN the
cerebrum ANd cerebellum of rAts giveN ebN
suPPlemeNtAtioN ANd exPosed to leAd AcetAte
e five experimental groups’ typical histological slices of
the cerebrum are displayed in Figure 1. Although there were
no obvious macroscopic pathological lesions in the rats, the
present study showed that lead had penetrated the blood-
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2157
brain barrier and altered the normal tissue architecture of
the brain. However, histomorphological examination of the
T0 group’s cerebrum revealed lead-induced histopatholog-
ical changes, including haemorrhage, edematous and vac-
uolated tissue with significant cell loss, and the appearance
of neural cell pyknotic nuclei (Figure 1).
Table 1: Description of clinical findings that appear after 5
weeks of LA and EBN administration.
Parameters C T0 T1 T2 T3
Aggression 0 2.50±0.50a1.50±.25b1.00±.25ab 0
Reduced appetite 0 2.50±0. 25a1.50±0.25b1.00±.25ab 0
Unable to coordinate
movement
0 2.00±0.50a1.00±0.25b0 0
e standarderror (SE) andmean ± expressed asthe data.
A significant difference at p < 0.05 is indicated by different
letters (a and b) within rows.
Figure 1: Histological changes in the cerebral cortex
of rats exposed to LA and treated with EBN. Note: e
control group displayed a typical. e T0 group displayed
haemorrhage and pyknotic nuclei, that considered signs
of degenerative changes in neural cells. T1 and T2 groups
demonstrated neuronal cell protection. T3 showed the
regeneration, resemble in the histo-architecture for control.
Table 2 displays the findings of the cerebrum’s histologi-
cal lesion scores. e cerebrallesions with vacuolations and
pyknotic neurons varied statistically significantly (p<0.05)
across the experimental groups, according to the data. Py-
knotic neurons and neural vacuolations were lowest in the
T2 group and higher in the T0 group (Figure 1). In con-
trast, T3 supplemented with the greatest dose of EBN ex-
hibited normal cerebral and cerebral cortex structures, sim-
ilar to those of the control group (Figure 1).
Table 2: Description of histopathological alterations of
cerebrum after LA and EBN administration at 5 weeks of
experimentation.
Parameters C T0 T1 T2 T3
histopathological
alterations
0 3.00±0.00a1.50±.25b 1.00±.25b0
e standard error (SE) and mean ± expressed as the data.
A significant difference at p < 0.05 is indicated by different
letters (a and b) within rows.
According to the current study, groups C and T3 have
normal morphological appearance of the cerebellar cortex
when stained with H&E (Figure 2). ese groups’ cellu-
lar morphology is typified by Purkinje cells with promi-
nent cell bodies and dendrites that protrude deeply into
the sparsely nucleated molecular layer (M), taking on the
form of a fan. Additionally, a large number of compactly
arranged tiny granule neurons make up the granule layer
(G) in T3 group (Figure 3).
Figure 2: Histological changes in the cerebellar cortex of
rats exposed to LA and treated with EBN. Note that darkly
stained degenerating pyramidal cells (black arrow) among
the healthy pyramidal neurons (yellow arrow) in T0, T1 and
T2. Cerebellar layers include molecular(M),purkinje(P)
and granular (G).
e cerebellar cortex of rats in the T0, T1, and T2 groups
showed histological changes in Purkinje and molecular lay-
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2158
er cells including shrinkage and degeneration, as well as dis-
persed glial cells. Purkinje’s cell layer completely separates
from the degenerating granular cell layer. Around the haz-
ily defined cerebellar layers, Purkinje cells with their typi-
cal pyknotic cell bodies and short dendritic processes may
be observed. Unlike the T3 group and the control group
the Purkinje cells exhibit empty spaces between the cells,
which indicates that the cells are degenerating. In addition,
the neutrophils in these groups have irregularly shaped and
sized neural cells, giving the impression of fragmentation.
Granular cells exhibit morphological deformation as well; in
comparison to the control. Moreover, nonparametric one-
way ANOVA was used to assess the impact of LA on the
cerebellum’s purkinje cells. Table 3 displays the findings of
the Purkinje cell histopathological lesion scores. e results
revealed a significant difference (p<0.05) in the neural le-
sions including vacuolations, pyknotic neurons, and necro-
sis among the experimental groups. e neural lesions were
lower in the T2 group and higher in the T0 group (Figure 3).
Figure 3: Histological changes in the cerebellar cortex
of rats exposed to LA and treated with EBN. Note that
the granule layer in T3 group consists of huge numbers
of small granule neurons. Cerebellar layers include
molecular(M),purkinje(P) and granular (G).
oxidAtive stress ANd ANtioxidANt biomArker
coNceNtrAtioNs
e current evaluation, the thiobarbituric acid reactive sub-
stance (TBARS) and TAC in the plasma from experimen-
tal groups are summarised in Figure 4. e highest con-
centration of TBARS was found in T0 (p<0.05), and the
lowest values were found in T3. In T1 and T2, there were
no notable alterations. At week 5, TAC levels increased in
accordance with thedose of EBNin the treatment groups.
TACs concentrations were higher in the T3 and decreased
(p<0.05) in the T0. ese effects improved the enzymatic
AO defense and raised the TAC, which altered the redox
status. ese findings suggest that EBN alters and weakens
the redox system.
Table 3: Description of histopathological alterations of
cerebellum after LA and EBN administration at 5 weeks
of experimentation.
Parameters C T0 T1 T2 T3
histopathological
alterations
0 3.00±0.00a2.00±.25b1.50±.25c0
e standarderror (SE) andmean ± expressed asthe data.
A significant difference at p < 0.05 is indicated by different
letters (a , b and c) within rows.
Figure 4: Impact of EBN on the activities of total antioxidant
capacity (TAC) and oxidative stress in the plasma of rats
exposed to LA. Reactive substance thiobarbituric acid
(TBARS). Informations are expressed as means ± S.E.M.
e primary factor contributing to the development of tox-
icity, which indicates significant pathological damages of
important organs, is oxidative stress brought on by expo-
sure to LA (Oyagbemi et al., 2015). Exposure to lead caus-
es encephalopathy, which is characterised by a progressive
deterioration of specific brain regions. e major symptoms
of encephalopathy include weariness, tremor in the mus-
cles, dullness, irritability, reduced attention span, memory
loss, and hallucinations. Elevated exposures result in more
severe symptoms such as ataxia, delirium, spasms, unable to
coordinate movement and coma (Verina et al., 2007). Sim-
ilarly, in the present study, rats exposed to LA has shown
clinical neurological symptoms including uncoordinat-
ed movement, aggression and reduced appetite while the
symptoms were observed significantly reduced in the EBN
supplemented group. Purkinje cells secrete gamma-amin-
obutyric acid that inhibits the transmission of nerve im-
pulses by acting on specific neurons. Purkinje cells are ca-
pable of coordinating and regulating motor movements by
virtue of their inhibitory functions (Britannica, 2015). e
clinical observations showed that rat exposure to lead ace-
tate alone was characterized by abnormal body movements
and inability to maintain balance due to neurotoxic effects
of lead on these cells causes damage and inflammations.
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2159
e neurotoxic effects of lead can be attributed to various
factors, such as interactions with other micronutrients, the
integrity of the blood-brain barrier, lead-binding proteins,
and cellular scavengers (e.g. glutathione(GSH)) (Sidhu and
Nehru, 2004). One of the ways in which lead damages the
central nervous system is by substituting numerous bivalent
cations (e.g., Ca2+, Mg2+, Fe2+) with Pb+ ions (Pb2+),
which allows lead to cross the blood-brain barrier (BBB)
and become trapped in the brain (Sanders et al., 2009).
Foetuses and children are particularly vulnerable to the
neurological implications of lead because their small in-
testine’s high absorption rate and the blood barrier is more
susceptible to heavy metals (Needleman, 2004). Even in
cases when lead exposure is minimal, children may exhibit
signs of hyperactivity, inattention, and irritability. Elevated
lead levels in children can cause hearing loss, short-term
memory loss, reduced understanding, and rapid develop-
ment. At higher concentrations, lead can result in lifelong
brain damage and possibly death (Cleveland et al., 2008).
e progressive deterioration of memory and cognition is
the consequence of severe morphological and function-
al deficits caused by the demise of neurons via apoptosis.
Natural antioxidants have been utilised to examine their
potential as metal lead chelating agents in the context of
lead-induced neurotoxicity (Singh et al., 2015; Singh et al.,
2016). EBN is one of the natural products reported as a
potential cognitive enhancer, including learning and mem-
ory abilities (Xie et al., 2018; Mahaq et al., 2020; Loh et al.,
2022). Since the Tang and Sung dynasties, EBN has been
widely used by humans as a tonic and medicinal diet in
traditional Chinese medicine (Zhao et al., 2016).
Histopathological findings of the present study showed
alterations such as shrinkage, degeneration as well as dis-
persed glial cells in the cerebellar and cerebral cortexes of
rats exposed to only LA while those supplemented with
highest dose of EBN demonstrated a preserved histomor-
phology alike the control group implying a protective role
played by the EBN supplement. Previous study revealed
that LA causes hypertension and the permeable blood–
brain barrier makes susceptible to lead exposure and sub-
sequent brain damage ( Järup, 2003; Vaziri and Sica, 2004).
Present study confirms these phenomena through conges-
tion of blood vessels and change histological structures. In
addition, Pb causes neural degeneration, cerebral oedema,
and cerebellar atrophy involving Purkinje, and granular
cells have been identified as complications that cause en-
cephalopathy in rats.
Prior in vitro research studies demonstrated that EBN ex-
tracts promoted neuronal differentiation, migration, and
proliferation by a substantial margin. A study conducted
by Yew et al. (2019) identified 29 bioactive proteins in
EBN extract that may play important roles in various com-
moncellular processes, including neurodevelopment, cell
proliferation, migration, formation of extracellular matrix
andantioxidation. EBN may also enable to regulate blood
hypertension via Angiotensin converting enzyme inhibito-
ry properties of EBN leading to make blood–brain barrier
more resistant for LA (Daud et al., 2019). In comparison
to rats treated solely with lead, the histopathological al-
terations induced by lead acetate in the brain regions were
significantly diminished and completely restored in the
EBN supplemented group.
Recent researches confirm the beneficial effect of an in-
creased intake of EBN in the treatment of neurodegen-
erative and neurological conditions (Careena et al., 2018).
EBN contains a diverse group of monosacharides such
as sialic acid that plays a distinctive role in repairing and
building the human body attributed to its therapeutic and
medicinal effects. It is associated with brain development,
neurological improvement and intellectual benefits in chil-
dren, as it serves as a functional portion of brain ganglio-
sides (Wang and Brand-Miller, 2003).
Glycosyl galactosamine (GalNAc), an essential compound
for the effective functioning of synapses, is frequently ob-
served to be glycosidically linked with sialic acid. Goh et al.
(2001) have demonstrated that GalNAc is also capable of
improving memory. Further, brain gangliosides, of which
sialic acid is a vital constituent, modified neural adhesion
cells and enhanced the neurotrophic factor involved in the
development of neurons and brain function. Schneider et
al. (2010) and Wang (2009) both asserted that sialic acid is
an essential component in cell-to-cell interactions. Angata
and Fukuda (2010) discovered that sialic acids have the
ability to regulate synaptic connectivity during memory
formation and stimulate neuron outgrowth, axon elonga-
tion, migration, and differentiation of NSC at the cellular
level. A prior study found that rats exposed to lead showed
a decrease in body weight compared to the control group
(Albishtue et al., 2019d). Lead exposure may be reduced
through interaction of lead with appetite-depressant re-
ceptors in the gastrointestinal tract (Hammond et al.,
1989), which is consistent with this research.
Neural stem cells are multipotent precursor cells that have
the capacity to generate new neurons, astrocytes, and oli-
godendrocytes, as well as to respond to trophic factors and
self-renew in order to recover functionally from neurode-
generative diseases. Research has indicated that the use of
endogenous resident stem cells in combination with ex-
ogenous neurotrophic support may be promising for the
restoration of damaged or degenerated neurons (Li et al.,
2013; Xu et al., 2014). Worth mentioning is the function-
al recovery exhibited by a number of natural neurotrophic
compounds. Xu et al. (2014) concluded that endogenous
neural stem cells are stimulate to an exogenous factor and
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2160
may be induced to assume specific cell phenotypes in re-
sponse to the application of suitable signals.
According to the earlier research, the administration of
LA raised oxidative stress levels that may lead to flaws in
the mitochondrial membrane’s permeability, allowing free
radicals and cytochrome c to exit the mitochondria and
bind to another protein known as apoptotic protease ac-
tivating factor-1 (Apaf-1), which in turn activates caspase
3 and causes cell death (Liu et al., 2012). Experimental
studies have demonstrated increased lipid peroxidation
and diminished antioxidant defense enzymes in the brain
following exposure to lead, indicating increased oxidative
stress (Velaga et al., 2014, Emam et al., 2023). Lead expo-
sure is also related to the depletion of brain GSH content
as shown by the ratio GSSG / GSSG + GSH (Adegbe-
san and Adenuga, 2007). It has been noted that lead forms
strong bonds with free-SH affinity groups in enzymes and
proteins, which can significantly impair the functionality
and efficacy of the enzymes in consideration. Lead-in-
duced neurotransmission was hypothesised to be mediated
by oxidative stress, which is generated when the antioxi-
dant equilibrium within the cells is disturbed; cell signal-
ling dysregulation and neurotransmission modification;
cell signalling deregulation and alteration of neurotrans-
mission were considered possible mechanisms involved in
lead-induced neurotransmission (Bokara et al., 2008). In
the present study, EBN supplementation showed a dose
dependant improvement of redox status of the rats exposed
to LA toxicity, the highest EBN dose supplement showing
a significant increase in TAC and reduction in lipid perox-
idation/MDA level.
EBN contains highly nutritious ingredients such as pro-
teins, mineral salts, vitamins, hormones, and fatty acids
(Saengkrajang et al., 2013). EBN supplement may have
protective effects because of its biological characteristics,
which include cell regeneration and proliferation (Mu-
hammad-Azam et al., 2022). EBN is very important for
avoiding any toxic effects after it is absorbed by cells. Ac-
cording to in-vitro research studies, EBN treatment in-
creased viability and proliferation of cell Caco-2 and neu-
roblastoma cell (Aswir and Wan Nazaimoon, 2011). is
observation could indicate that EBN is absorbed by cells
with functional mitochondria, leading to an increase in cell
viability absorbance and a potent signal (Mosmann, 1983).
EBN contains a high amount of sialic acid which has cer-
tain molecular mechanisms that regulate the proliferation
of cells by the hormone E2. A diet high in sialic acid re-
ported to increase the number of brain cells in mammals
and promotes the expression of genes linked to cognition
(Careena et al., 2018).
Sialic acid has anti-inflammatory properties, capable of
modulating an extensive type of physiological and patho-
logical processes. For example, EBN extract may also re-
duce the release of factor-alpha (TNF-α) tumour necrosis
in a macrophage cell line of a mouse leukaemic monocyte
(Aswir and Wan Nazaimoon, 2011). Furthermore, it ex-
hibits a stimulating impact on cell growth and regenera-
tion due to its Epidermal Growth Factor (EGF)-like ac-
tivity (Zhiping et al., 2015). Present study has found that
treated group possess highest numbers of glomerular and
Purkinje cells even than control although it exposed to LA.
In numerous conditions, including anti-aging, anti-cancer,
and immunity enhancement, the EBN has been utilised as
a prophylactic hormonal replacement agent. EBN consist
of progesterone, testosterone, estradiol, LH, FSH, and pro-
lactin (Ma and Liu., 2012; Albishtue et al., 2019c).
According to Jin et al. (2001), EBN is also recognised for
its composition of VEGF and IL-6, which inhibit cell
apoptosis by preventing the activation of caspase three
and thereby retinal neuronal apoptosis. Irusta et al. (2010)
found that VEGF, FSH, and estradiol inhibit caspase 3
activation, promote proliferation, and prevent apoptosis in
a synergistic manner. Evidently regulating inflammatory
and antioxidant genes, EBN has numerous therapeutic ap-
plications (Yida et al., 2015).
Pb is capable of traversing the blood-brain barrier and
causing damage to glial cells specifically targeting the cer-
ebral cortex, cerebellum, and hippocampus, thereby dis-
rupting the structural components of the brain (Gandhi
and Abramov., 2012, Al-Khafaf et al., 2021). Due to their
diminished capacity to detoxify reactive oxygen species
(ROS), neurons are susceptible to increases in ROS lev-
els, which can be generated by lead intoxication (Dringen
et al., 2005). us, altering the histology and neurological
functions of the cerebrum and cerebellum. Components
of EBN reduced H2O2-induced cytotoxicity and ROS
via enhanced scavenging activity, according to a previous
study. In addition, EBN induced transcriptional modifica-
tions in genes associated with antioxidants that exhibited a
propensity for neuroprotection. Furthermore, EBN and its
constituents, lactoferrin and ovotransferrin, have the po-
tential to generate synergistic antioxidative effects due to
their respective antioxidative capacities (Hou et al., 2015).
e current study demonstrated the antioxidant properties
of EBN by reversing the impact of lead toxicity on MDA
and TAC levels. is reversal may be a result of the high
concentration of antioxidant factors in the EBN sample.
Lead toxicity may be mitigated through additional supple-
mentation of EBN, thereby preserving the phospholipid
ratio in the cell membrane. As a result, it is hypothesised
that EBN provides protection against lead neurotoxicity
via the aforementioned mechanisms and by preventing
lead accumulation in the brain via urine elimination.
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2161
CONCLUSIONS AND
RECOMMENDATIONS
is study revealed that histological alterations of the cer-
ebrum and cerebellum were associated with exposure to
lead acetate. EBN could be considered a health-enhancing
medicinal food against neurodegenerative diseases. Over-
all, antioxidant and anti-inflammatory properties of EBN
were significantly higher in EBN 60 and 120 mg/kg bwt.
Finally, it can be deduced that EBN significantly inhibits
neuroinflammatory and oxidative stress processes that can
potentially lead to enhanced memory and potent neuro-
protection. However, further research studies and clinical
trials in humans would be needed to ascertain the benefits
of EBN supplement observed in the present study using
animal models and to determine the appropriate doses.
ACKNOWLEDGEMENTS
e authors would like to thank UPM for providing
fund for this project through the Impactful Putra Grant
scheme with project code, UPM.RMC.800-3/3/1/
GPB/2020/9688900 and vote no. 9688900.
NOVELTY STATEMENT
e present study revealed potential neuroprotective func-
tion of EBN against heavy metal (lead) toxicity using rats
as a model.
list of AbbreviAtioNs
ANOVA= Analysis of variance
ANOVA= a one-way analysis of variance
AO= Antioxidant
Apaf-1= apoptotic protease activating factor-1
Bwt= Body weight
CNS= central nervous system
CNS= Central nervous system
EBN= edible bird’s nest
FSH= Follicular stimulating hormone
GalNAc= Glycosyl galactosamine
GalNAc= Glycosyl galactosamine
GSH= Glutathione
H and E= Using hematoxylin and eosin
H2O2= Hydrogen peroxide
IACUC= the institutional animal care recommendations
and use committee
LA= Lead acetate
LH= Luteinizing hormone
LPO= lipid peroxidation
OSB= Oxidative Stress biomarker
Pb= Lead
TBARS= iobarbituric acid reactive substance
TCA= total antioxidant capacity
TNF-α= factor-alpha
AUTHOR’S CONTRIBUTIONS
is study was conceptualized by AAA, NY, MZAZ, AWH
and ASB. e investigations were performed by AAA and
NY, under the supervision of NY, MZAZ, AWH, and
ASB. Statistical analysis was carried out by AAA and NY.
Original manuscript was written by AAA, reviews and ed-
iting were finalized by AAA, NY, MZAZ, AWH and ASB.
e final manuscript was read and approved by all authors.
coNflict of iNterest
e authors declare that they have no conflict of interest.
REFERENCES
Adegbesan BO, Adenuga GA (2007). Effect of lead exposure on
liver lipid peroxidative and antioxidant defense systems of
protein-undernourished rats. Biol. Trace Elem. Res. 116:219-
25. https://doi.org/10.1007/s12011-007-9029-8
Albishtue AA, Yimer N, Zakaria MZA, Haron AW, Babji
AS, Abubakar AA, Almhanawi BH (2019d). Effects of
EBN on embryo implantation, plasma concentrations of
reproductive hormones, and uterine expressions of genes of
PCNA, steroids, growth factors and their receptors in rats.
eriogenology,126: 310-319. https://doi.org/10.1016/j.
theriogenology.2018.12.026
Albishtue A, Yimer N, Zakaria M, Haron A, Babji A, Abubakar
A, Almhanna H, Baiee F, Almhanawi B( 2019c). Edible
bird’s nest’s role and mechanism in averting lead acetate
toxicity effect on rat’s uterus, Vet. World, 12(7): 1013-1021.
https://doi.org/10.14202/vetworld.2019.1013-1021
Albishtue A, Yimer N, Zakaria M, Haron A, Yusoff R, Assi M,
Almhanawi B (2018e). Edible bird’s nest impact on rats’
uterine histomorphology, expressions of genes of growth
factors and proliferating cell nuclear antigen, and oxidative
stress level, Vet. World, 11 (1): 71-79. https://doi.
org/10.14202/vetworld.2018.71-79
Albishtue AA, Yimer N, Zakaria MZA, Haron AW, Yusoff R,
Almhanawi BH (2018b). Ameliorating effect of edible bird’s
nest against lead acetate toxicity on the rat hypothalamic–
pituitary–ovarian axis and expressions of epidermal growth
factor and vascular endothelial growth factor in ovaries.
Comp. Clin. Path., 1-11. https://doi.org/10.1007/
s00580-018-2729-y
Albishtue AA, Almhanna HK, Yimer N, Zakaria MZA, Haron
AW, Almhanawi BH (2020a). Effect of Edible Bird’s Nest
Supplement on Hepato-renal Histomorphology of Rats
Exposed to Lead Acetate Toxicity. Jordan J. Biol. Sci., 13(2).
Al-Khafaf A, Ismail HK, Alsaidya A (2021). Histopathological
effects of experimental exposure to lead on nervous system
in albino female rats. Iraqi J. Vet. Med., 35(1): 45-8. https://
doi.org/10.33899/ijvs.2019.126248.1273
Al-Quraishy S, Dkhil MA, Ibrahim SR, Moneim AEA (2016).
Neuroprotective potential of Indigofera oblongifolia
leaf methanolic extract against lead acetate-induced
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2162
neurotoxicity. Neural Regen. Res., 11(11):1797. https://
doi.org/10.4103/1673-5374.194749
Angata K, Fukuda M (2010). Roles of polysialic acid in migration
and differentiation of neural stem cells. Meth. Enzymol. 479:
Elsevier. p. 25-36. https://doi.org/10.1016/S0076-
6879(10)79002-9
Assi M, Abba Y, Abdulkhaleq L, Hezmee M, Haron A, Yusof
M, Rajion MA, Al-Zuhairy MA (2018). Effect of powdered
seed of Nigella sativa administration on sub-chronic
and chronic lead acetate induced hemato-biochemical
and histopathological changes in Sprague Dawley rats.
Comparative Clin. Pathol. 27:705-16. https://doi.
org/10.1007/s00580-018-2655-z
Aswir A, Wan Nazaimoon W (2011). Effect of edible bird’s nest
on cell proliferation and tumor necrosis factor-alpha release
in vitro. Int. Food Res. J., 18(3).
Barkur RR, Bairy LK (2015). Assessment of oxidative stress in
hippocampus, cerebellum and frontal cortex in rat pups
exposed to lead (Pb) during specific periods of initial brain
development. Biol. Trace Elem. Res., 164:212-8. https://
doi.org/10.1007/s12011-014-0221-3
Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna
S, Bettaiya R (2008). Lead-induced increase in antioxidant
enzymes and lipid peroxidation products in developing rat
brain. Biometals, 21:9-16. https://doi.org/10.1007/
s10534-007-9088-5
Britannica (2015). e Editors of Encyclopaedia. “Purkinje
cell”. Encyclopedia Britannica, 15 May. 2015, https://
www.britannica.com/science/Purkinje-cell. Accessed 20
November 2023
Careena S, Sani D, Tan S, Lim C, Hassan S, Norhafizah M, Kirby
BP, Ideris AJ, Bin Basri H (2018). Effect of edible bird’s nest
extract on lipopolysaccharide-induced impairment of learning
and memory in wistar rats. Evid. Based Complementary
Altern. Med. https://doi.org/10.1155/2018/9318789
Chen L, Liu Y, Jia P, Zhang H, Yin Z, Hu D, Ning H, Ge Y.
(2022). Acute lead acetate induces neurotoxicity through
decreased synaptic plasticity-related protein expression and
disordered dendritic formation in nerve cells. Environ. Sci.
Pollut. Res. 29(39), 58927-58935. https://doi.org/ 10.1007/
s11356-022-20051-1.
Cleveland LM, Minter ML, Cobb KA, Scott AA, German VF
(2008). Lead hazards for pregnant women and children: part
1: immigrants and the poor shoulder most of the burden of
lead exposure in this country. Part 1 of a two-part article
details how exposure happens, whom it affects, and the
harm it can do. Am. J. Nurs., 108(10):40-9. https://doi.
org/10.1097/01.NAJ.0000337736.76730.66
Daud NA, Mohamad Yusop S, Babji AS, Lim SJ, Sarbini SR,
Hui Yan T (2019). Edible bird’s nest: physicochemical
properties, production, and application of bioactive extracts
and glycopeptides. Food Rev. Int., 37(2):177-96. https://
doi.org/10.1080/87559129.2019.1696359
Dringen R, Pawlowski PG, Hirrlinger J (2005). Peroxide
detoxification by brain cells.J. Neurosci. Res., 79(1‐2):157-
65. https://doi.org/10.1002/jnr.20280
Emam MA, Farouk SM, Aljazzar A, Abdelhameed AA, Eldeeb
AA, Gad FA-m (2023). Curcumin and cinnamon mitigates
lead acetate-induced oxidative damage in the spleen of rats.
Front. pharmacol., 13:1072760. https://doi.org/10.3389/
fphar.2022.1072760
Flora G, Gupta D, Tiwari A(2012). Toxicity of lead: a review with
recent updates. Interdiscip. Toxicol, 5(2):47-58. https://
doi.org/10.2478/v10102-012-0009-2
Flora S (2002). Nutritional components modify metal
absorption, toxic response and chelation therapy.
J. Nutr. Environ. Med., 12(1):53-67. https://doi.
org/10.1080/13590840220123361
Gandhi S, Abramov AY(2012). Mechanism of oxidative stress in
neurodegeneration. Oxid. Med. Cell. Longev. https://doi.
org/10.1155/2012/428010
Goh DLM, Chua KY, Chew FT, Liang RCMY, Seow TK,
Ou KL, Yi FC, Lee BW (2001). Immunochemical
characterization of edible bird’s nest allergens. J. Allergy Clin.
Immunol., 107(6):1082-8. https://doi.org/10.1067/
mai.2001.114342
Hammond P, Chernausek S, Succop P, Shukla R, Bornschein
R (1989). (rats. Toxicol. Appl. Pharmacol. 99(3):474-86.
https://doi.org/10.1016/0041-008X(89)90155-5
Horiguchi H, Oguma E, Sasaki S, Okubo H, Murakami K,
Miyamoto K, Hosoi Y, Murata K, Kayama F (2013).
Age-relevant renal effects of cadmium exposure through
consumption of home-harvested rice in female Japanese
farmers. Environ. Int., 56:1-9. https://doi.org/10.1016/j.
envint.2013.03.001
Hossain S, Bhowmick S, Jahan S, Rozario L, Sarkar M,
Islam S, Basunia MA,Rahman A, Choudhury BK,
Shahjalal H (2016). Maternal lead exposure decreases
the levels of brain development and cognition-related
proteins with concomitant upsurges of oxidative stress,
inflammatory response and apoptosis in the offspring rats.
Neurotoxicology, 56:150-8. https://doi.org/10.1016/j.
neuro.2016.07.013
Hou Z, Imam MU, Ismail M, Azmi NH, Ismail N, Ideris
A, Mahmud R (2015). Lactoferrin and ovotransferrin
contribute toward antioxidative effects of Edible Bird’s Nest
against hydrogen peroxide-induced oxidative stress in human
SH-SY5Y cells. Biosci. Biotechnol. Biochem., 79(10): 1570-
8. https://doi.org/10.1080/09168451.2015.1050989
Ibrahim NM, Eweis EA, El-Beltagi HS, Abdel-Mobdy YE
(2012). Effect of lead acetate toxicity on experimental male
albino rat. Asian Pac. J. Trop. Biomed., 2(1):41-6. https://
doi.org/10.1016/S2221-1691(11)60187-1
Irusta G, Abramovich D, Parborell F, Tesone M (2010). Direct
survival role of vascular endothelial growth factor (VEGF) on
rat ovarian follicular cells. Mol. Cell. Endocrinol., 325(1):93-
100. https://doi.org/10.1016/j.mce.2010.04.018
Järup L (2003). Hazards of heavy metal contamination. Br. Med.
Bull., 68(1):167-82. https://doi.org/10.1093/bmb/
ldg032
Jin K, Mao X, Batteur S, McEachron E, Leahy A, Greenberg D
(2001). Caspase-3 and the regulation of hypoxic neuronal
death by vascular endothelial growth factor. Neuroscience,
108(2):351-8. https://doi.org/10.1016/S0306-
4522(01)00154-3
Kalia K, Flora SJ (2005). Strategies for safe and effective
therapeutic measures for chronic arsenic and lead poisoning.
J. Occup. Health. 47(1): 1-21. https://doi.org/10.1539/
joh.47.1
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2163
Kasperczyk S, Birkner E, Kasperczyk A, Kasperczyk J (2005).
Lipids, lipid peroxidation and 7-ketocholesterol in workers
exposed to lead. Hum. Exp. Toxicol., 24(6):287-95. https://
doi.org/10.1191/0960327105ht528oa
Li R, Liang T, Xu L, Zheng N, Zhang K, Duan X (2013).
Puerarin attenuates neuronal degeneration in the substantia
nigra of 6-OHDA-lesioned rats through regulating BDNF
expression and activating the Nrf2/ARE signaling pathway.
Brain Res., 1523:1-9. https://doi.org/10.1016/j.
brainres.2013.05.046
Liu C-M, Ma J-Q, Sun Y-Z (2012). Puerarin protects the rat
liver against oxidative stress-mediated DNA damage and
apoptosis induced by lead. Exp. Toxicol. Pathol., 64(6): 575-
82. https://doi.org/10.1016/j.etp.2010.11.016
Liu E, Yan T, Birch G, Zhu Y (2014). Pollution and health risk
of potentially toxic metals in urban road dust in Nanjing, a
mega-city of ChinaSci. Total Environ., 476: 522-31. https://
doi.org/10.1016/j.scitotenv.2014.01.055
Liu JT, Dong MH, Zhang JQ, Bai Y, Kuang F, Chen LW (2015).
Microglia and astroglia: the role of neuroinflammation in
lead toxicity and neuronal injury in the brain. Neuroimmunol.
Neuroinflamm., 2:131-7. https://doi.org/10.4103/2347-
8659.156980
Loh SP, Cheng SH, Mohamed W (2022). Edible bird’s nest as
a potential cognitive enhancer. Front. Neurol., 13: 865671.
https://doi.org/10.3389/fneur.2022.865671
Mahaq OP, Rameli MA, Jaoi Edward M, Mohd Hanafi N, Abdul
Aziz S, Abu Hassim Noor H, Ahmad M (2020). e effects
of dietary edible bird nest supplementation on learning and
memory functions of multigenerational mice. Brain Behav.
10(11): e01817. https://doi.org/10.1002/brb3.1817
Ma F, Liu D (2012). Sketch of the edible bird’s nest and its
important bioactivities. Int. Food Res. J., 48(2):559-67.
https://doi.org/10.1016/j.foodres.2012.06.001
Mosmann T (1983). Rapid colorimetric assay for cellular growth
and survival: application to proliferation and cytotoxicity
assays. J. Immunol. Methods, 65(1-2):55-63. https://doi.
org/10.1016/0022-1759(83)90303-4
Muhammad-Azam F, Nur-Fazila SH, Ain-Fatin R, Noordin
MM, YasminAR, Yimer N (2022). Prophylactic effect of
edible bird’s nest on acetaminophen-induced liver injury
response in mice model. Pak. J. Pharm. Sci., 35(1).
Needleman H (2004). Lead poisoning. Annu Rev
Med.55:209-22. https://doi.org/10.1146/annurev.
med.55.091902.103653
Otong ES, Musa SA, Danborno B, Sambo SJ, Dibal NI (2022).
Adansonia digitata ameliorates lead-induced memory
impairments in rats by reducing glutamate concentration and
oxidative stress. Egypt. j. basic appl. sci., 9(1): 1-10. https://
doi.org/10.1080/2314808X.2021.2009678
Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB,
Ogunpolu BS, Daramola O (2015). Lack of reversal of
oxidative damage in renal tissues of lead acetate‐treated
rats. Environ. Toxicol., 30(11):1235-43. https://doi.
org/10.1002/tox.21994
Rzymski P, Rzymski P, Tomczyk K, Niedzielski P, Jakubowski
K, Poniedziałek B, Opala T (2014). Metal status in
human endometrium: relation to cigarette smoking and
histological lesions. Environ. Res., 132:328-33. https://doi.
org/10.1016/j.envres.2014.04.025
Saengkrajang W, Matan N, Matan N (2013). Nutritional
composition of the farmed edible bird’s nest (Collocalia
fuciphaga) in ailand. J. Food Compos. Anal., 31(1):41-5.
https://doi.org/10.1016/j.jfca.2013.05.001
Sanders T, Liu Y, Buchner V, Tchounwou PB (2009). Neurotoxic
effects and biomarkers of lead exposure: a review. Rev.
Environ. Health, 24(1): 15-46. https://doi.org/10.1515/
REVEH.2009.24.1.15
Satarug S, Baker JR, Reilly PE, Moore MR, Williams DJ (2002).
Cadmium levels in the lung, liver, kidney cortex, and urine
samples from Australians without occupational exposure to
metals. Arch. Environ. Health: Int J., 57(1): 69-77. https://
doi.org/10.1080/00039890209602919
Schmidt CM, Blount JD, Bennett NC (2014). Reproduction is
associated with a tissue-dependent reduction of oxidative
stress in eusocial female Damaraland mole-rats (Fukomys
damarensis). PloS one, 9(7): e103286. https://doi.
org/10.1371/journal.pone.0103286
Schneider JS, Sendek S, Daskalakis C, Cambi F (2010). GM1
ganglioside in Parkinson’s disease: Results of a five year
open study. J. Neurol. Sci., 292(1-2): 45-51. https://doi.
org/10.1016/j.jns.2010.02.009
Shukla PK, Khanna VK, Khan MY, Srimal RC (2003).
Protective effect of curcumin against lead neurotoxicity
in rat. Hum. Exp. Toxicol., 22(12):653-8. https://doi.
org/10.1191/0960327103ht411oa
Sidhu P, Nehru B (2004). Lead intoxication: histological and
oxidative damage in rat cerebrum and cerebellum. J. Trace
Elem. Exp. Med. e Official Publication of the Int.
Soc. Trace Elem. Res. Hum., 17(1): 45-53. https://doi.
org/10.1002/jtra.10052
Singh P, Rawat A, Dixit R, Kumar P, Nath R (2015). Behavioral
and neurochemical effects of omega-3 fatty acids against lead
aetate exposure in male wistar rats: an experimental study.
Int. J. Curr. Res., 7(9): 20936-44.
Singh PK, Nath R, Ahmad MK, Rawat A, Babu S, Dixit RK
(2016). Attenuation of lead neurotoxicity by supplementation
of polyunsaturated fatty acid in Wistar rats. Nutr. Neurosci.,
19(9): 396-405. https://doi.org/10.1179/147683051
5Y.0000000028
Vaziri ND, Sica DA (2004). Lead-induced hypertension: role of
oxidative stress. Curr. Hypertens. Rep., 6(4):314-20. https://
doi.org/10.1007/s11906-004-0027-3
Velaga MK, Basuri CK, Robinson Taylor KS, Yallapragada PR,
Rajanna S, Rajanna B (2014). Ameliorative effects of Bacopa
monniera on lead-induced oxidative stress in different
regions of rat brain. Drug Chem. Toxicol., 37(3): 357-64.
https://doi.org/10.3109/01480545.2013.866137
Verina T, Rohde CA, Guilarte TR (2007). Environmental lead
exposure during early life alters granule cell neurogenesis
and morphology in the hippocampus of young adult
rats. Neuroscience, 145(3): 1037-47. https://doi.
org/10.1016/j.neuroscience.2006.12.040
Wang B (2009). Sialic acid is an essential nutrient for
brain development and cognitionAnnu. Rev. Nutr.,
29: 177-222. https://doi.org/10.1146/annurev.
nutr.28.061807.155515
Wang B, and Brand-Miller J (2003). e role and potential of
sialic acid in human nutrition. Eur J Clin Nutr, 57(11), 1351-
1369. https://doi.org/ 10.1038/sj.ejcn.1601704
Advances in Animal and Veterinary Sciences
November 2024 | Volume 12 | Issue 11 | Page 2164
Xie Y, Zeng H, Huang Z, Xu H, Fan Q, Zhang Y (2018). Effect
of maternal administration of edible bird’s nest on the
learning and memory abilities of suckling offspring in mice.
Neural Plast., https://doi.org/10.1155/2018/7697261
Xu J, Lacoske MH, eodorakis EA (2014). Neurotrophic natural
products: chemistry and biology. Angew. Chem. Int. Ed.,
53(4):956-87. https://doi.org/10.1021/np5003516
Yew MY, Koh RY, Chye SM, Abidin SAZ, Othman I, Ng KY
(2019). Neurotrophic properties and the de novo peptide
sequencing of edible bird’s nest extracts. Food Biosci., 32:
100466. https://doi.org/10.1016/j.fbio.2019.100466
Yew MY, Koh RY, Chye SM, Othman I, Ng KY (2014). Edible
bird’s nest ameliorates oxidative stress-induced apoptosis in
SH-SY5Y human neuroblastoma cells. BMC Complement
Altern. Med.,14(1): 391. https://doi.org/10.1186/1472-
6882-14-391
Yida Z, Imam MU, Ismail M, Ooi D-J, Sarega N, Azmi NH,
Ismail N, Chan KW, Hou Z, Yusuf NB (2015). Edible bird’s
nest prevents high fat diet-induced insulin resistance in rats. J.
Diabetes Res., https://doi.org/10.1155/2015/760535
Zhao R, Li G, Kong Xj, Huang Xy, Li W, Zeng Yy, Lai Xy (2016).
e improvement effects of edible bird’s nest on proliferation
and activation of B lymphocyte and its antagonistic effects
on immunosuppression induced by cyclophosphamide. Drug
Des. Devel er., 371- 81. https://doi.org/10.2147/
DDDT.S88193
Zhiping H, Imam MU, Ismail M, Ismail N, Yida Z, Ideris
A, Sarega N , Mahmud R (2015). Effects of edible bird’s
nest on hippocampal and cortical neurodegeneration in
ovariectomized rats. Food Funct., 6(5): 1701-11. https://
doi.org/10.1039/C5FO00226E
