Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model
Lifestyle modifications, such as physical exercise and dietary supplements, were recommended as protective measures against some neurological disorders. We examined the effects of regular exercise combined with curcumin supplementation against lead-induced oxidative damage of the cerebellum in ma...
Збережено в:
| Дата: | 2016 |
|---|---|
| Автори: | , , |
| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Інститут фізіології ім. О.О. Богомольця НАН України
2016
|
| Назва видання: | Нейрофизиология |
| Онлайн доступ: | http://dspace.nbuv.gov.ua/handle/123456789/148153 |
| Теги: |
Додати тег
Немає тегів, Будьте першим, хто поставить тег для цього запису!
|
| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Protective Effects of Regular Exercise Combined with Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model / M. Habibian, S. J. Moosavi, P. Farzanegi // Нейрофизиология. — 2016. — Т. 48, № 1. — С. 20-25. — Бібліогр.: 36 назв. — англ. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
irk-123456789-148153 |
|---|---|
| record_format |
dspace |
| spelling |
irk-123456789-1481532019-02-18T01:24:58Z Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model Habibian, M. Moosavi, J. Farzanegi, P. Lifestyle modifications, such as physical exercise and dietary supplements, were recommended as protective measures against some neurological disorders. We examined the effects of regular exercise combined with curcumin supplementation against lead-induced oxidative damage of the cerebellum in male rats. Experimental animals (n = 50) were randomly divided into five groups. Lead acetate (20 mg/kg) was i.p. administered to three groups (except sham and control ones), while the sham group received ethyloleate (30 mg/kg) three times per week. The curcumin and curcumin + exercise groups received curcumin (30 mg/kg) i.p. five times per week for eight weeks. The exercise program consisted of progressive running on a treadmill, speed from 15 to 22 m/min, 25 to 64 min per day, five times per week for eight weeks. Two days after the last application, the rats were euthanized, and their cerebellum was removed and homogenized to measure the levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARSs). Chronic administration of lead significantly increased the cerebellar TBARS levels but did not alter considerably the BDNF levels. Curcumin and curcumin + exercise treatments significantly lowered the cerebellar TBARS levels; a significant increase in the BDNF level was observed in the cerebellum of rats treated with combined intervention. Thus, regular exercise combined with curcumin supplementation may exert a significant neuroprotective effect against lead-induced cerebellar injury by attenuating oxidative stress and improving the brain state through an increase in the BDNF amount. Модифікації стилю життя, такі як фізичні тренування та вживання добавок до дієти, рекомендуються як протективні заходи щодо низки неврологічних розладів. Ми дослідили впливи регулярних тренувань, поєднаних з уведенням куркуміну, на індуковане свинцевою інтоксикацією оксидативне ушкодження мозочка у самців щурів. Експериментальні тварини (n = 50) були рандомізовано поділені на п’ять груп. Ацетат свинцю (20 мг/кг) уводився тваринам трьох груп (дві слугували контролем). Одна з контрольних груп отримувала етилолеат (30 мг/кг) тричі на тиждень. У двох інтоксикованих групах тварини отримували 30 мг/кг куркуміну п’ять разів на тиждень протягом восьми тижнів. Програма тренувань включала в себе прогресивно збільшувані епізоди бігу на тредбані (від 15 до 25 м/хв, від 25 до 64 хв/добу, п’ять разів на тиждень протягом восьми тижнів). Через дві доби після закінчення курсів щурів піддавали евтаназії, мозочок видаляли та гомогенізували для вимірювання рівнів мозкового нейротрофічного фактора (BDNF) та речовин, реактивних щодо тіобарбітурової кислоти (TBARSs). Хронічне введення свинцю викликало вірогідне збільшення рівнів TBARS, але не змінювало істотно рівнів BDNF. У групах «куркумін» та «куркумін+тренування» спостерігалися значно нижчі рівні TBARS; вірогідно більший рівень BDNF у мозочку відмічався в групі з комбінацією заходів. Отже, регулярні фізичні тренування, поєднані з уведенням куркуміну, можуть забезпечити істотний протекторний ефект щодо індукованого свинцем ушкодження мозочка, опосередкований зменшенням оксидативного стресу та поліпшенням стану мозку завдяки певному збільшенню кількості BDNF. 2016 Article Protective Effects of Regular Exercise Combined with Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model / M. Habibian, S. J. Moosavi, P. Farzanegi // Нейрофизиология. — 2016. — Т. 48, № 1. — С. 20-25. — Бібліогр.: 36 назв. — англ. 0028-2561 http://dspace.nbuv.gov.ua/handle/123456789/148153 616.099 en Нейрофизиология Інститут фізіології ім. О.О. Богомольця НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| description |
Lifestyle modifications, such as physical exercise and dietary supplements, were recommended
as protective measures against some neurological disorders. We examined the effects of
regular exercise combined with curcumin supplementation against lead-induced oxidative
damage of the cerebellum in male rats. Experimental animals (n = 50) were randomly divided
into five groups. Lead acetate (20 mg/kg) was i.p. administered to three groups (except sham
and control ones), while the sham group received ethyloleate (30 mg/kg) three times per
week. The curcumin and curcumin + exercise groups received curcumin (30 mg/kg) i.p. five
times per week for eight weeks. The exercise program consisted of progressive running on
a treadmill, speed from 15 to 22 m/min, 25 to 64 min per day, five times per week for eight
weeks. Two days after the last application, the rats were euthanized, and their cerebellum
was removed and homogenized to measure the levels of brain-derived neurotrophic factor
(BDNF) and thiobarbituric acid-reactive substances (TBARSs). Chronic administration
of lead significantly increased the cerebellar TBARS levels but did not alter considerably
the BDNF levels. Curcumin and curcumin + exercise treatments significantly lowered the
cerebellar TBARS levels; a significant increase in the BDNF level was observed in the
cerebellum of rats treated with combined intervention. Thus, regular exercise combined with
curcumin supplementation may exert a significant neuroprotective effect against lead-induced
cerebellar injury by attenuating oxidative stress and improving the brain state through an
increase in the BDNF amount. |
| format |
Article |
| author |
Habibian, M. Moosavi, J. Farzanegi, P. |
| spellingShingle |
Habibian, M. Moosavi, J. Farzanegi, P. Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model Нейрофизиология |
| author_facet |
Habibian, M. Moosavi, J. Farzanegi, P. |
| author_sort |
Habibian, M. |
| title |
Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model |
| title_short |
Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model |
| title_full |
Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model |
| title_fullStr |
Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model |
| title_full_unstemmed |
Protective Effects of Regular Exercise Combined With Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model |
| title_sort |
protective effects of regular exercise combined with curcumin supplementation against lead-induced cerebellar oxidative damage in an animal model |
| publisher |
Інститут фізіології ім. О.О. Богомольця НАН України |
| publishDate |
2016 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/148153 |
| citation_txt |
Protective Effects of Regular Exercise Combined with Curcumin Supplementation Against Lead-Induced Cerebellar Oxidative Damage in an Animal Model / M. Habibian, S. J. Moosavi, P. Farzanegi // Нейрофизиология. — 2016. — Т. 48, № 1. — С. 20-25. — Бібліогр.: 36 назв. — англ. |
| series |
Нейрофизиология |
| work_keys_str_mv |
AT habibianm protectiveeffectsofregularexercisecombinedwithcurcuminsupplementationagainstleadinducedcerebellaroxidativedamageinananimalmodel AT moosavij protectiveeffectsofregularexercisecombinedwithcurcuminsupplementationagainstleadinducedcerebellaroxidativedamageinananimalmodel AT farzanegip protectiveeffectsofregularexercisecombinedwithcurcuminsupplementationagainstleadinducedcerebellaroxidativedamageinananimalmodel |
| first_indexed |
2025-07-12T18:28:11Z |
| last_indexed |
2025-07-12T18:28:11Z |
| _version_ |
1837466802328698880 |
| fulltext |
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 120
UDC 616.099
M. HABIBIAN1, S. J. MOOSAVI1,2, and P. FARZANEGI2
PROTECTIVE EFFECTS OF REGULAR EXERCISE COMBINED WITH CURCUMIN
SUPPLEMENTATION AGAINST LEAD-INDUCED CEREBELLAR OXIDATIVE
DAMAGE IN AN ANIMAL MODEL
Received June 11, 2014
Lifestyle modifications, such as physical exercise and dietary supplements, were recommended
as protective measures against some neurological disorders. We examined the effects of
regular exercise combined with curcumin supplementation against lead-induced oxidative
damage of the cerebellum in male rats. Experimental animals (n = 50) were randomly divided
into five groups. Lead acetate (20 mg/kg) was i.p. administered to three groups (except sham
and control ones), while the sham group received ethyloleate (30 mg/kg) three times per
week. The curcumin and curcumin + exercise groups received curcumin (30 mg/kg) i.p. five
times per week for eight weeks. The exercise program consisted of progressive running on
a treadmill, speed from 15 to 22 m/min, 25 to 64 min per day, five times per week for eight
weeks. Two days after the last application, the rats were euthanized, and their cerebellum
was removed and homogenized to measure the levels of brain-derived neurotrophic factor
(BDNF) and thiobarbituric acid-reactive substances (TBARSs). Chronic administration
of lead significantly increased the cerebellar TBARS levels but did not alter considerably
the BDNF levels. Curcumin and curcumin + exercise treatments significantly lowered the
cerebellar TBARS levels; a significant increase in the BDNF level was observed in the
cerebellum of rats treated with combined intervention. Thus, regular exercise combined with
curcumin supplementation may exert a significant neuroprotective effect against lead-induced
cerebellar injury by attenuating oxidative stress and improving the brain state through an
increase in the BDNF amount.
Keywords: lead toxicity, brain-derived neurotrophic fact, cerebellar injury, oxidative
stress, physical exercise, curcumin.
1 Department of Physical Education and Sports Sciences, Qaemshahar Branch,
Islamic Azad University, Qaemshahar, Iran.
2 Department of Physical Education and Sports Sciences, sari Branch, Islamic
Azad University, Sari, Iran.
Correspondence should be addressed to S. J. Moosavi
(e-mail: moosavi.s.j@gmail.com , moosavi_j@yahoo.com).
INTRODUCTION
Lead is a toxic heavy metal [1]; recognition of and
prevention against its harmful effects are an important
international public health priority [2]. Human lead
exposure remains a serious occupational and public
health problem in humans [3]. The half-life of lead
in the blood is rather long [4], and its levels in the
brain decrease very slowly [5]. Immediate effects of
lead include alteractions in chemistry, physiology, and
histology of the brain [6]. It has been reported that
lead intoxication cause several abnormalities in the
CNS, such as cognitive impairments, neurobehavioral
disorders, and neurodegeneration [7]. Previous studies
have indicated that lead can induce significant injuries
in the cerebellum, to both histological characteristics
and antioxidant capacity of this brain structure [1, 6].
Lead-induced oxidative stress has been known to
play a crucial role in the pathogenesis of lead intoxi-
cation, so that significant amounts of reactive oxygen
species (ROSs) generated due to lead exposure were
detected in brain [8]. Because the brain is character-
ized by a high oxygen tension, low mitotic rate, high
lipid content, and low antioxidant concentrations, it is
very susceptible to oxidative damage [9]. Bennet et al.
[10] indicated a region-specific oxidative stress in rat's
brain exposed to lead so that high-intensity oxidative
stress was observed in the hippocampus and cerebel-
lum compared to other regions of the rat brain.
There is evidence that neurotrophins can play a sig-
nificant protective role in the mammalian nervous sys-
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 1 21
PROTECTIVE EFFECTS OF EXERCISE AND CURCUMIN AGAINST Pb-INDUCED INTOXICATION
tem [11]. Brain-derived neurotrophic factor (BDNF), a
member of the neurotrophin family of growth factors,
contributes to the survival, function, and plasticity of
neurons in the adult brain [12]. Radak et al. [13] re-
ported that accumulation of oxidative damage in the
brain associated with impaired brain functions can in-
teract with the function of the BDNF system [14].
Physical exercise can help to maintain a sufficient
brain health and plasticity throughout life; it is an im-
portant public health goal [15]. Such exercise has a ca-
pability to alter the level of BDNF and the rate of oxi-
dative damage in the brain of animals [16]. Seifert et
al. [17] indicated that expression of BDNF in the rat
hippocampus and release of BDNF in the human brain
increased following endurance training. Besides, exer-
cise effects and nutritional antioxidants (curcumin in
particular) can protect the brain from oxidative stress
[18, 19]. Curcumin (diferuloylmethane) is a polyphe-
nol compound derived from the Curcuma longa plant
and known as turmeric. It has been demonstrated that
curcumin has a wide range of therapeutic properties,
including antioxidant, analgesic, anti-inflammatory,
and antiseptic activities [20]. Curcumin demonstrates a
powerful scavenging activity against ROSs [21] and can
protect neural cells from oxidative stress [20]. On the
other hand, both ROSs and BDNF are common molec-
ular targets for the action of the diet and exercise [22].
Most investigations of lead-related damage were fo-
cused on the effects of lead on the histological struc-
ture of the cerebellum [1, 6]. It, however, remained
unclear how a combination of physical exercise with
curcumin treatment influences lead-induced oxidative
stress in the rat cerebellum. Therefore, we studied the
effect of regular long-lasting exercise (rather similar
to human exercise training) combined with curcumin
supplementation on lead-induced cerebellar oxidative
damage in an animal model.
METHODS
Chemicals. Lead acetate, ethyloleate, curcumin,
ketamine, xylazine, sodium chloride, Tris-HCl, NP40,
glycerol, phenylmethylsulfonyl fluoride (PMSF),
leupeptin, sodium vanadate, and 4-(2-aminoethyl)-
benzenesulfonyl fluoride hydrochloride (AEBSF)
were obtained from Sigma-Aldrich (USA). TBARS
and BDNF test kits were purchased from Cayman
Chemical Co. (USA) and R&D Systems (USA).
Animals. The experiments were performed on male
Wistar rats (250 ± 4 g, eight to ten weeks old) kept
with free access to a standard pellet diet and water. All
animals were obtained from the Pasture Institute of
Iran and were housed in polycarbonate cages (five per
cage) at a temperature of (22 ± 2°C) and humidity of
(50 ± 5%), with the 12h/12h dark/light cycles.
Experimental Procedure. Fifty normal Wister
rats matched for the age and body mass were ran-
domly divided into five groups (10 animals each)
and treated as follows. The control group received
no treatment; the sham group received ethyloleate
(i.p., 30 mg/kg body mass) for three days per week
over eight weeks; the lead group received lead ace-
tate (i.p., 20 mg/kg [23]) for three days per week over
eight weeks; the curcumin group received the same
lead doses, but plus curcumin (i.p., 30 mg/kg [23] for
five days per week over eight weeks, and the exer-
cise plus curcumin group received the same curcumin
doses, but the animals performed aerobic exercises.
The mode of the latter was the following; after one
week of familiarization to a treadmill (KN-73, Nat-
sume, Japan), exercise-group rats performed train-
ing at 15 m/min, 25 min per day with 0% grade for
five days at the first week. Gradual increases in the
training speed and duration were subsequently estab-
lished such that the rats reached a speed of 22 m/min
for 64 min per day at the end of the eighth week. This
protocol was designed according to the maximum oxy-
gen consumption. In every exercise session, 3 min-
long run at the speed of 7 m/min was increased by
2 m/min for each minute until the desired speed was
reached. A cool-down program was performed via a
gradual decrease in the treadmill speed to approach the
initial speed set at the beginning of the program [24].
Anesthesia and Tissues Collection. After the
last applications (48 h) and overnight fasting (12 h),
the animals were sacrificed under anesthesia by i.p.
administration of a mixture of ketamine (60 mg/kg)
and xylazine (5 mg/kg). The brains were removed,
and cerebellum tissues were kept at –70ºC before
biochemical examination.
B i o c h e m i c a l A n a l y s i s . E n z y m e - l i n k e d
immunosorbant assay [ELISA] was performed for
BDNF according to the manufacturer’s guidelines
[25]. The level of TBARS, as a byproduct of lipid
peroxidation, was measured by a TBARS kit (Cayman
Chemicals, USA) in accordance with the method of
Nabavi et al. [26, 27].
Statistical Analysis. Data are shown below as
means ± s.e.m. Statistical analysis was performed with
a one-way ANOVA and post-hoc testing by the Tukey’s
test. P values < 0.05 were considered indications of
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 122
M. HABIBIAN, S. J. MOOSAVI, and P. FARZANEGI
statistically significant intergroup differences. All
statistical tests were performed using a commercial
software package (SPSS version 16.0 for Windows).
RESULTS
The results in Table 1 show that means of the body and
brain masses of lead-treated rats decreased relative to
the respective values in the sham (7.4 and 4.7%, re-
spectively) and control groups (7.5% and 6.3%, re-
spectively), but these shifts were statistically insigni-
ficant. The above changes in the body and brain mass-
es were, however, noticeably smaller following ad-
ministration of curcumin alone and that combined
with regular exercise treatments (P < 0.05).
Cerebellar TBARS levels significantly increased
in lead-administered rats, as compared with those
in the sham and control groups (0.564 ± 0.045 vs.
0.315 ± 0.048 and 0.315 ± 0.075 nmol/mg MDA
eq/g tissue, respectively, P = 0.000). Both curcumin
supplementation alone and the combination of
curcumin and regular exercise led to significant
decreases in the cerebellar TBARS levels (0.384 ±
± 0.058 and 0.377 ± 0.066 nmol/mg MDA eq/g tissue
respectively, P = 0.000). No significant difference was
observed between the effects of both interventions on
the intensity of lipid peroxidation in rat brain tissues
(Fig. 1A). Furthermore, lead acetate administration
exerted no significant effect on the cerebellar BDNF
levels (2.59 ± 1.98 ng/mg protein) when compared
with those in the sham and control groups (2.53 ±
2.03 and 2.21 ± 1.12 ng/mg protein, respectively).
Eight week-long combined intervention significant-
ly (more than two times) increased the cerebellar
BDNF level (6.15 ± 1.73 ng/mg protein), compared
with the respective values in the control (P = 0.030),
sham (P = 0.014), and lead (P = 0.044) groups.
Supplementation with curcumin provided a noticeable
increase (4.68 ± 2.96 ng/mg protein) in the cerebellar
BDNF level in lead-treated rats, but the diference did
not reach the significance level (Fig. 1B).
0.8
nmol/mg
0.6
0.4
0.2
0
Contr. Sham Lead Curcumin Exercise+
+curcumin
8
ng/mgA
*
#B
6
4
2
0
Contr. Sham Lead Curcumin Exercise+
+curcumin
F i g 1. Mean cerebellar TBARS (A) and BDNF (B) levels in groups of the rats after eight weeks of treatment. *P < 0.001 vs. the control,
sham, curcumin, and exercise +curcumin groups; #P < 0.05 vs. the control, sham, and lead groups. Values are shown as means ± s.e.m. for
ten rats; TBARS: thiobarbituric acid-reactive substances; BDNF: brain-derived neurotrophic factor.
Р и с. 1. Середні рівні TBARS (A) та BDNF (B) у групах щурів через вісім тижнів після початку експерименту.
Effect of regular physiological exercise combined with curcumin supplementation on the body and brain mass during chronic lead
administration in rats
Вплив регулярних фізичних тренувань, поєднаних із споживанням куркуміну, на масу тіла та масу мозку щурів в умовах
хронічної інтоксикації свинцем
Indices Control Sham Lead acetate Lead +
+ curcumin
Lead + curcumin+
+ exercise
Body mass (g) 342.12 ±9.00 341.75 ±12.31 316.57± 9.14 322.00 ±8.54 343.38± 15.32
Brain mass (g) 1.73 ± 0.15 1.70 ± 0. 18 1.62 ± 0.29 1.72 ± 0.10 1.79 ± 0.07
Footnote: values are shown as means ± s.e.m. for 10 rats.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 1 23
PROTECTIVE EFFECTS OF EXERCISE AND CURCUMIN AGAINST Pb-INDUCED INTOXICATION
DISCUSSION
In our study, lead was i.p. administered to male
Wistar rats at a dose of 20 mg/kg body mass for eight
weeks. At the end of the treatment period, decreases
in the body and brain masses of the treated rats were
observed when compared with the respective indices
in sham and control animals, but these changes did not
reach the significance level. Comparable observations
of the lead effects were described by other authors
[6, 28]. Sidhu and Nehru [29] reported that the mass
of both cerebrum and cerebellum decreased in lead-
intoxicated rats, and such shifts in the experiments of
these authors were significant. The normal arrangement
of three layers in the cerebellum was modified enough
to disrupt the normal arrangement of the molecular
layer, Purkinje cell layer, and granular cell layer of
the cerebellum after lead treatment [6]. Lead toxicity
can intensely damage normal histological structure of
the brain, modify morphological characteristics of the
nerve cells and ganglia in the CNS, and alter normal
functions performed by them [7]. These shifts perhaps
explain why lead exposure affected somewhat the
brain mass in our study.
We found that chronic lead administration in rats
significantly increased the TBARS level in the cere-
bellum, but this pathophysiological change was not
accompanied by significant changes in the cerebel-
lar BDNF level (Fig. 1B). Earlier studies [6, 29, 30]
have established that exposure of rats to lead caused
an increase in the intensity of lipid peroxidation and
decreased the activity of antioxidant enzymes in the
cerebellum, compared with the controls. Lead neuro-
toxicity in the brain is mediated by oxidative stress
to a considerable extent, which forwardly implies to
depletion of antioxidant enzyme stores. Lead acts as
a nonspecific enzyme inhibitor due to its high affin-
ity for sulfhydryl groups in protein molecules [6, 31].
In addition, lead accumulation in tissues increases the
level of δ-aminolevulinic acid, and this intensifies oxi-
dative stress and impairs the membranes, DNA, and
proteins [31]. However, increased oxidative stress ob-
served in our study exerted no dramatic influence on
the cerebellar BDNF level, and we failed to detect the
respective effect. In contrast, Hosseinzadeh et al. [32]
reported a significant decrease in the hippocampal
BDNF level, which was accompanied by an increase
(while insignificant) in the intensity of lipid peroxida-
tion in rats exposed to lead acetate. It seems that the
effects of lead on the BDNF levels in various regions
of the brain do not appear to be uniform.
As shown in Fig. 1A, both curcumin supplementa-
tion alone and such treatment combined with regular
physical exercise led to comparable significant de-
creases in the cerebellar TBARS levels in lead-intoxi-
cated rats. These positive changes were accompanied
by elevations in the cerebellar BDNF levels. Com-
bined regular exercise and curcumin treatment syn-
ergistically induced a higher BDNF level than either
treatment alone. This protective effect of curcumin
agrees with findings of Shukla et al. [29] who demon-
strated a significant increase in the antioxidant defense
and a decreased intensity of lipid peroxidation in the
cerebellum, corpus striatum, hippocampus, and fron-
tal cortex in rats simultaneously treated with curcumin
and lead. Similar effects were found in the hippocam-
pus of male rats after eight weeks of combination of
continuous exercise training and curcumin treatment
in another study [32]. Although the exact mechanisms
by which exercise or curcumin treatment counteracts
lead-induced cerebellar injuries are mostly unclear, it
should be mentioned that we observed a synergistic ef-
fect of these influences on the cerebellar BDNF level
following combined intervention. It seems that both
curcumin and regular physical exercise cause paral-
lel changes in the oxidative stress and promote the re-
spective repair mechanisms in the brain. Curcumin as
a powerful antioxidant agent (known to be a scavenger
of superoxide anions, hydroxyl radicals, and nitrogen
dioxide, and also as a hydrogen donor) exhibits the an-
tioxidant activity directly and also indirectly protects
the brain against various oxidative stressors [33].
The biological function of BDNF is exerted through
binding to its receptor, tropomyosin-related kinase B
(TrkB), which initiates multiple signaling cascades
[34]. Curcumin produces neuroprotective effects,
in particular via activating brain-derived neurotro-
phic factor/TrkB-dependent MAPK and PI-3K cas-
cades [35]. Also, it was reported that both moderate
treadmill running and wheel running in animal experi-
ments up-regulate the BDNF-TrkB pathway in the hip-
pocampus [29]. Exercise exerts its neuroprotective ef-
fects on the brain through several mechanisms. In fact,
it is clear that voluntary exercise can increase the lev-
els of BDNF and other growth factors, stimulate neuro-
genesis, and increase the resistance to brain insult
[15]. Thus, generation of cerebellar BDNF may form a
considerable protective response to lead-induced ox-
idative stress, because BDNF acts not only via pro-
tection of the existing neurons, but also via intensifi-
cation of neurogenesis and improvement of synaptic
plasticity [36].
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 124
M. HABIBIAN, S. J. MOOSAVI, and P. FARZANEGI
In conclusion, regular physical exercise combined
with curcumin supplementation may provide rather
significant neuroprotective effects against lead-
induced cerebellar injury by attenuating oxidative
stress; these influences improve brain health in
particular through an increase in the BDNF level.
Acknowledgment. This study was supported by the
Qaemshahar Branch, Islamic Azad University, Project No.
1391.
The experimental protocol followed the US National
Institutes of Health guidelines for the care and use of laboratory
animals and was approved by the Institutional Animal Care and
Use Committee (Approval number: No. 03-19-5/15819 1390
IAU).
The authors, M. Habibian, S. J. Moosavi, and P. Farzanegi,
confirm that they have no conflict of interest with any
organization or person that may be related to this study; there
was also no conflict of interest in interrelations between the
authors.
M. Хабібян1, С. Дж. Мусаві1,2, П. Фарзенегі2
ПРОТЕКТИВНИЙ ВПЛИВ КОМБІНАЦІЇ ФІЗИЧНОГО
ТРЕНУВАННЯ ТА ВВЕДЕННЯ КУРКУМІНУ НА ІНДУ-
КОВАНЕ СВИНЦЕВОЮ ІНТОКСИКАЦІЄЮ ОКСИДА-
ТИВНЕ УШКОДЖЕННЯ МОЗОЧКА В ЕКСПЕРИМЕН-
ТАЛЬНІЙ МОДЕЛІ
1 Квемшахарський відділ Ісламського університету Азад
(Іран).
2 Сарійський відділ Ісламського університету Азад (Іран).
Р е з ю м е
Модифікації стилю життя, такі як фізичні тренування та
вживання добавок до дієти, рекомендуються як протективні
заходи щодо низки неврологічних розладів. Ми дослідили
впливи регулярних тренувань, поєднаних з уведенням кур-
куміну, на індуковане свинцевою інтоксикацією оксидатив-
не ушкодження мозочка у самців щурів. Експериментальні
тварини (n = 50) були рандомізовано поділені на п’ять груп.
Ацетат свинцю (20 мг/кг) уводився тваринам трьох груп (дві
слугували контролем). Одна з контрольних груп отримува-
ла етилолеат (30 мг/кг) тричі на тиждень. У двох інтоксико-
ваних групах тварини отримували 30 мг/кг куркуміну п’ять
разів на тиждень протягом восьми тижнів. Програма трену-
вань включала в себе прогресивно збільшувані епізоди бігу
на тредбані (від 15 до 25 м/хв, від 25 до 64 хв/добу, п’ять ра-
зів на тиждень протягом восьми тижнів). Через дві доби піс-
ля закінчення курсів щурів піддавали евтаназії, мозочок ви-
даляли та гомогенізували для вимірювання рівнів мозкового
нейротрофічного фактора (BDNF) та речовин, реактивних
щодо тіобарбітурової кислоти (TBARSs). Хронічне введен-
ня свинцю викликало вірогідне збільшення рівнів TBARS,
але не змінювало істотно рівнів BDNF. У групах «куркумін»
та «куркумін+тренування» спостерігалися значно нижчі рів-
ні TBARS; вірогідно більший рівень BDNF у мозочку від-
мічався в групі з комбінацією заходів. Отже, регулярні фі-
зичні тренування, поєднані з уведенням куркуміну, можуть
забезпечити істотний протекторний ефект щодо індукова-
ного свинцем ушкодження мозочка, опосередкований змен-
шенням оксидативного стресу та поліпшенням стану мозку
завдяки певному збільшенню кількості BDNF.
REFERENCES
1. Y. Wang and S. Wang, “Effects of lead exposure on histological
structure and antioxidant capacity in the cerebellum of 30-day-
old mice,” Neural. Regen. Res., 6, 1077-1081 (2011).
2. M. Ahamed and M. K. Siddiqui, “Low level lead exposure
and oxidative stress: current opinion,” Clin. Chim. Acta, 383,
57-64 (2007).
3. R. Jabeen, M. Tahir, and S. Waqas, “Teratogenic effects of
lead acetate on kidney,” J. Ayub. Med. Coll. Abbottabad., 22,
76-79 (2010).
4. L. Patrick, “Lead toxicity part II: The role of free radical
damage and the use of antioxidants in the pathology and
treatment of lead toxicity,” Altern. Med. Rev., 11, 114-127
(2006).
5. M. F. Collins, P. D. Hrdina, E. Whittle, et al., “Lead in blood
brain regions of rats chronically exposed to low doses of the
metal,” Toxicol. Appl. Pharmacol., 65, 314-332 (1982).
6. P. Sidhu and B. Nehru, “Lead intoxication: histological and
oxidative damage in rat cerebrum and cerebellum,” J. Trace
Elem. Exp. Med., 17, 45-53 (2004).
7. J. Hsiang and E. Díaz, “Lead and developmental neurotoxicity
of the central nervous system,” Current Neurobiol., 2, 35-42
(2011).
8. P. C. Hsu and Y. L. Guo, “Antioxidant nutrients and lead
toxicity,” Toxicology, 180, 33-44 (2002).
9. D. Julka, R. Pal, and K. D. Gill, “Neurotoxicity of dichlorvos:
effect on antioxidant system in the rat central nervous system,”
Exp. Mol. Pathol., 56, 144 (1992).
10. C. Bennet, R. Bettaiya, S. Rajanna, et al., “Region specific
increase in the antioxidant enzymes and lipid peroxidation
products in the brain of rats exposed to lead,” Free Radic.
Res., 41(3), 267-273 (2007).
11. R. M. Lindsay, S. J. Wiegand, C. A. Altar, et al., “Neurotrophic
factors: from molecule to man,” Trends Neurosci., 17, 182-190
(1994).
12. G. R. Lewin and Y. A. Barde, “Physiology of the
neurotrophins,” Annu. Rev. Neurosci., 19, 289-231 (1996)
13. Z. Radák, T. Kaneko, S. Tahara, et al., “Regular exercise
improves cognitive function and decreases oxidative damage
in rat brain,” Neurochem. Int., 38, 17-23 (2001).
14. A. Wu, Z. Ying, and F. Gomez-Pinilla, “The interplay between
oxidative stress and brain-derived neurotrophic factor
modulates the outcome of a saturated fat diet on synaptic
plasticity and cognition,” Eur. J. Neurosci., 19, 1699-1707
(2004).
15. C. W. Cotman and N. C. Berchtold, “Exercise: a behavioral
intervention to enhance brain health and plasticity,” Trends
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2016.—T. 48, № 1 25
PROTECTIVE EFFECTS OF EXERCISE AND CURCUMIN AGAINST Pb-INDUCED INTOXICATION
Neurosci., 25, 295-301 (2002).
16. Z. Radak, A. Toldy, Z. Szabo, et al., “The effects of training
and detraining on memory, neurotrophins and oxidative stress
markers in rat brain,” Neurochem. Int., 49, 387-392 (2006).
17. T. Seifert, P. Brassard, M. Wissenberg, et al., “Endurance
training enhances BDNF release from the human brain,” Am.
J. Physiol. Regul. Integr. Comp. Physiol., 298, R372-R377
(2010).
18. A. Acar, E. Akil, H. Alp, et al., “Oxidative damage is
ameliorated by curcumin treatment in brain and sciatic nerve
of diabetic rats,” Int. J. Neurosci., 122, 367-372 (2012).
19. A. Rajeswari, “Curcumin protects mouse brain from
oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine,” Eur. Rev. Med. Pharmacol. Sci., 10, 157-
161 (2006).
20. R. Wilken, M. S. Veena, M. B. Wang, et al., “Curcumin: A
review of anti-cancer properties and therapeutic activity in
head and neck squamous cell carcinoma,” Mol. Cancer, 10, 12
(2011).
21. S. F. Nabavi, M. Daglia, A. H. Moghaddam, et al., “Curcumin
and liver disease: from chemistry to medicine,” Compr. Rev.
Food Sci. Food Saf., 13(1), 62-77 (2014).
22. R. Molteni, A. Wu, S. Vaynman, et al., “Exercise reverses the
harmful effects of consumption of a high-fat diet on synaptic
and behavioral plasticity associated to the action of brain-
derived neurotrophic factor,” Neuroscience, 123, 429-440
(2004).
23. S. Daniel, J. L. Limson, A. Dairam, et al., “Through metal
binding, curcumin protects against lead- and cadmium-induced
lipid peroxidation in rat brain homogenates and against lead-
induced tissue damage in rat brain,” J. Inorg. Biochem., 98,
266-275 (2004).
24. R. A. Johnson, J. S. Rhodes, S. L. Jeffrey, et al., “Hippocampal
brain-derived neurotrophic factor but not neurotrophin-3
increases more in mice selected for increased voluntary wheel
running,” Neuroscience, 121, 1-7 (2003).
25. M. Peeri, M. Habibian, M. A. Azarbayjani, et al., “Protective
effect of aerobic exercise against L-NAME-induced kidney
damage in rats,” Arh. Hig. Rada. Toksikol., 64, 43-49 (2013).
26. S. M. Nabavi, S. F. Nabavi, S. Eslami, et al., “In vivo protective
effects of quercetin against sodium fluorideinduced oxidative
stress in the hepatic tissue,” Food Chem., 132, 931-935 (2012).
27. S. F. Nabavi, S. M. Nabavi, M. Mirzaei, et al., “Protective
effect of quercetin against sodium fluoride induced oxidative
stress in rat’s heart,” Food Funct., 3(4), 437-441 (2012).
28. N. M. Ibrahim, E. A. Eweis, H. S. El-Beltagi, et al., “Effect of
lead acetate toxicity on experimental male albino rat,” Asian
Pac. J. Trop. Biomed., 2, 41-46 (2012).
29. P. K. Shukla, V. K. Khanna, M. Y. Khan, et al., “Protective
effect of curcumin against lead neurotoxicity in rat,” Hu-
man Exp. Toxicol., 22, 653-638 (2003).
30. K. K. Bokara, E. Brown, R. McCormick, et al., “Lead-induced
increase in antioxidant enzymes and lipid peroxidation
products in developing rat brain,” Biometals, 21, 9-16 (2008).
31. R. C. Patra, A. K. Rautray, and D. Swarup, “Oxidative stress
in lead and cadmium toxicity and its amelioration,” Vet. Med.
Int., 457327 (2011).
32. S. Hosseinzadeh, V. D. Roshan, and S. Mahjoub, “Continuous
exercise training and curcumin attenuate changes in brain-
derived neurotrophic factor and oxidative stress induced by
lead acetate in the hippocampus of male rats,” Pharm. Biol.,
51, 240-245 (2013)
33. G. M. Cole, B. Teter, and S. A. Frautschy, “Neuroprotective
effects of curcumin,” Adv. Exp. Med. Biol., 595, 197-212
(2007).
34. R. Klein, V. Nanduri, S. A. Jing, et al., “The trkB tyrosine
protein kinase is a receptor for brain-derived neurotrophic
factor and neurotrophin-3,” Cell, 26(66), 395-403 (1991).
35. Y. H. Li, Y. Xu, Y. B. Li, et al., “Curcumin produces
neuroprotect ive effects via act ivat ing brain-derived
neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades
in rodent cortical neurons,” Prog. Neuropsychopharmacol.
Biol. Psychiat., 34, 147-53 (2010).
36. M. K. McGovern, “The effects of exercise on the brain,” http://
serendip.brynmawr.edu/bb/deuro 2005. 4-25.
|