Download Exercise Training and Antioxidants: Effects on Rat Heart

Exercise Training and Antioxidants:
Effects on Rat Heart Tissue Exposed
to Lead Acetate
International Journal of Toxicology
30(2) 190-196
ª The Author(s) 2011
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DOI: 10.1177/1091581810392809
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Valiollah Dabidi Roshan1, Mohammad Assali1,
Akbar Hajizadeh Moghaddam3, Mahdi Hosseinzadeh1, and
Jonathan Myers3
Abstract
We have investigated the cardioprotective effects of exercise training and/or curcumin on lead acetate-induced myocardial
damage. Forty rats were randomly divided into 5 groups: (1) lead acetate, (2) curcumin, (3) endurance training, (4) training þ
curcumin, (5) sham groups. The rats in groups 3 and 4 experienced the treadmill running of 15 to 22 m/min for 25 to 64 minutes,
5 times a week for 8 weeks. Groups 1 to 4 received lead acetate (20 mg/kg), the sham group received curcumin solvent
(ethyl oleat), and the curcumin and training þ curcumin groups received curcumin solution (30 mg/kg) intraperitoneally. Lead
administration resulted in significant increases in high-sensitivity C-reactive protein (hs-CRP), creatine kinase-MB (CK-MB),
malondialdehyde (MDA), and low-density lipoprotein (LDL), and significantly decreased glutathione peroxidase (GPx), Total Antioxidant Capacity (TAC), and high-density lipoprotein (HDL) levels. Treadmill running and\or curcumin supplementation resulted
in a significant decrease in hs-CRP, CK-MB, MDA, and LDL levels and significantly increased GPx, TAC, and HDL levels. These
results suggest a lifestyle-induced cardioprotective potential in ameliorating lead-induced cardiotoxicity.
Keywords
endurance training, antioxidants, lead, heart damage, rat
Introduction
Cardiovascular disease (CVD) is the major cause of mortality
worldwide and recent studies have shown that there is an association between CVD, inflammation, and oxidative stress.1,2
Recently, the American Heart Association (AHA) published
a scientific statement on the importance of air pollution in the
development of cardiovascular disease.1 Lead is a ubiquitous
environmental toxin that induces a broad range of physiological, biochemical, and behavioral dysfunctions. Its toxicity
has been known from ancient times and affects organs with
low antioxidant defense such as the heart.2-5 Recent studies
have revealed the potential for lead to induce oxidative stress,
and evidence has accumulated supporting the role of oxidative stress in the pathophysiology of lead poisoning.2,3 Toxic
metals increase production of free radicals and decrease the
availability of antioxidant reserves to respond to the resultant
damage.3 The toxicity of lead is mainly connected with its
influence on the enzymatic systems of cells, which leads to
many biochemical disorders. It has been suggested that lead
takes part in the formation of free oxygen radicals.6 Several
studies have reported decreases in antioxidant enzyme activities such as glutathione peroxidase (GPx) and increases in
inflammation and/or heart injury in lead-exposed animals
and workers.2,3,6
Cardiovascular diseases are invariably followed by several
biochemical alterations such as lipid peroxidation, free radical
damage, hyperglycemia, and hyperlipidemia, which lead to
qualitative and quantitative alterations of myocardium.7 Recent
studies have revealed that generation of free radicals can lead
to significant injuries2,3,7; hence, free radical scavengers (antioxidants) can be used as an important therapeutic method to
prevent these injuries. An abundance of research suggests that
lifestyle changes, including antioxidant therapy and regular
physical training, are important in order to prevent chronic diseases. Despite considerable progress in the management of cardiac events by synthetic drugs, the search for indigenous
cardioprotective agents continues.
1
Faculty of Physical Education and Sport Sciences, Department of Exercise
Physiology, University of Mazandaran, Babolsar, Iran
2
Faculty of Biology, University of Mazandaran, Babolsar, Iran
3
Cardiology Division, VA Palo Alto Health Care System, Stanford University,
Palo Alto, CA, USA
Corresponding Author:
Valiollah Dabidi Roshan, The University of Mazandaran (UMZ) Pasdaran Street,
47415, P.O. Box: 416, Babolsar, Iran
Email: [email protected] or [email protected]
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Dabidi Roshan et al
191
100
0.30
*
0.25
*#
*#
hs - CRP (mg / L)
CK- MB (U / L)
80
#
60
40
20
0
0.15
0.10
#
#
0.05
Sham
Lead
0.00
Training Curcumin Training
& Curcumin
Lead Acetate (20 mg/kg)
Sham
Lead
Training Curcumin Training
& Curcumin
Lead Acetate (20 mg/kg)
80
50
*
60
40
#
HDL (mg / dL)
LDL (mg / dL)
*
0.20
#
#
40
#
#
#
30
20
20
10
0
0
Sham
Lead
Training
& Curcumin
Lead Acetate (20 mg/kg)
10
Lead
Training
& Curcumin
Lead Acetate (20 mg/kg)
Training Curcumin
600
* # ¥$
500
8
* #
#¥
* #
6
TAC (mol / mL)
GPx (m of GSH utilised / mg protein)
Sham
Training Curcumin
*
4
2
0
* #
* #
400
*
300
200
100
0
Sham
Lead
Training
& Curcumin
Lead Acetate (20 mg/kg)
Training Curcumin
Sham
Lead
Training Curcumin
Training
& Curcumin
Lead Acetate (20 mg/kg)
60
**
MDA (nmol / mL)
50
#
40
#
#
30
20
10
0
Sham
Lead
Training
& Curcumin
Lead Acetate (20 mg/kg)
Training Curcumin
Figure 1. Creatine kinase-MB (CK-MB), high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein (LDL), high-density lipoprotein
(HDL), glutathione peroxidase (GPx), Total Antioxidant Capacity (TAC), and malondialdehyde (MDA) concentrations in experimental animals.
Statistical significance P < .05: *Significantly different than sham group; # Significantly different than lead group; ¥ Significantly different than training þ lead group; $ significantly different than curcumin þ lead group.
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International Journal of Toxicology 30(2)
Recent emphasis on the use of natural and complementary
medicines has drawn the attention of the scientific community
to the potential of these treatment options. Curcumin {1,7bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione}
(diferuloyl methane), the principle coloring agent present in the
rhizomes of Curcuma longa (also known as turmeric) has a
long history in traditional medicine. It has many therapeutic
properties including antioxidant, anti-inflammatory, and
anticancer activities. In addition, it is a powerful scavenger
of free radicals.4,8 Moreover, it has been suggested to have a
wide range of therapeutic effects in numerous conditions
including chronic inflammatory diseases such as CVD. While
research in this area has mainly focused on anticancer effects
of curcumin and several clinical trials using curcumin have
shown promising results in cancer therapy, studies of curcumin
on other diseases, including CVD, are lacking. There has been a
great deal of attention paid to the role of lipid peroxidation and
antioxidant effects of physical training in the recent years.
Many studies have reported that acute submaximal exercise
increases exercise-induced lipid peroxidation. Regular physical
training, on the other hand, causes an increase in the antioxidant system and a reduction in lipid peroxidation.9 It has been
suggested that individuals who exercise regularly and therefore
place a consistent oxidative stress on their muscles and other
cells have an augmented antioxidant defense system to reduce
exercise-induced oxidative risk.9 A meta-analysis from the
Cochrane Database has shown that exercise training is highly
effective in reducing mortality in patients with coronary artery
disease (CAD).10 Despite the knowledge that lead can induce
oxidative stress, studies have identified favorable effects of
exercise training and/or antioxidants on certain cardiovascular
biomarkers after acute exposure to air pollution.8 However,
there are few data available with respect to concomitant effects
of regular aerobic training and antioxidant supplementation,
particularly the oxidant/antioxidant and inflammatory processes that underlie heart tissue injury during chronic exposure
to lead acetate.
The purpose of the current study was therefore to determine
the effects of aerobic exercise, curcumin supplementation, or
both of them on biomarkers of oxidative stress (GPx, Total
Antioxidant Capacity (TAC), and malondialdehyde [MDA]),
inflammatory (high-sensitivity C-reactive protein [hs-CRP]),
and heart tissue injury (creatine kinase-MB [CK-MB]) in rats
that have been chronically exposed to lead acetate. It is
hypothesized that the results of this study provide novel insight
about the cardiac ameliorative potential of curcumin and exercise training.
Materials and Methods
The experimental protocol was approved by Department of
Physiology, University of Mazandaran, and was performed
according to guiding procedures in the Care and Use of Animals, prepared by the Council of the American Physiological
Society. Forty male Wistar rats, 8 weeks of age (initial body
weight of 240 + 20 g), were obtained from the Laboratory
of Animal Bearing and Multiplying at the Pasture Institute of
Iran. Each rat was housed in single standard cages of polycarbonate (20 15 15), made at the Pasture Institute of Iran, in
a large air-conditioned room with controlled temperature of 22
+ 2 C, light-dark cycles of 12:12 hours and humidity of 50%
+ 5%. The pollutant standard index (PSI) was in the acceptable range as determined by the Iranian Meteorological Organization. Rats were fed with a standard rat chow provided by Pars
Institute for animals and poultry with a daily regimen of 10 /
100 g body weight for each rat. Water was available ad libitum.
Rats were familiarized with the laboratory environment and
running on the treadmill, then were randomly assigned into 5
experimental groups of 8 rats each. The groups were defined
as follows: group1—the animals were exposed to lead acetate
at a concentration of 20 mg/kg in the form of a water solution
(for intraperitoneal [ip] injection), 3 days weekly for 8 weeks;
group 2—Curcumin (Cum) similarly received lead acetate, as
well as curcumin 30 mg/kg 5 days weekly for 8 weeks (ip);
group 3—endurance training (Pb þ training) —the rats in this
group similarly received lead acetate, and in addition they performed progressive running exercise of 15 to 22 m/min for 25
to 64 minutes, 5 times a week; group 4—training and curcumin
(Pb þ training þ Cum); the rats in this group performed a physical training protocol similar to that in group 3, and in addition
received lead acetate and curcumin supplementation; group
5—the sham-operate or control group (sham); these rats
received water and ethyl oleate, in the same manner and for the
same duration of time as other groups. Lead acetate (Sigma)
was solubilized in Milli-Q water, and curcumin was solubilized
in 50% ethanol. In order to perform ip injections, curcumin
was solubilized in ethyl oleate and was injected at a dose of
30 mg/kg. Curcumin was protected from light throughout the
experiment.4 We are replicating a previously-reported leaddosing regimen that caused oxidative stress so that the doses of
Curcumin and lead acetate were 30 and 20 mg/kg, respectively.4
All groups were anesthetized with ketamine and Xaylozine
and decapitated after 12 to 14 hours overnight fasting.
Blood samples were collected 24 hours after the last dose of
treatment. These blood samples were initially centrifuged by
a refrigerated centrifuge at 3000 rpm for 15 minutes within
30 minutes of collection and then stored at 80 C before assay;
serum was separated for biochemical estimations of blood
lipids and CK-MB. The body cavities were then opened and the
heart was quickly excised from the aortic root. Heart tissues
were weighed and placed into Petri dishes containing cold
isolation medium (0.1 mol/L K2HPO4, 0.15 mol/L NaCl,
pH ¼ 7.4) to remove the blood and were frozen immediately
in liquid nitrogen and stored at 80 C for subsequent analysis
of hs-CRP, MDA, and GPx.
Tissues were homogenized in ice-cold 10 mmol/L Tris-HC1,
pH 8.2, containing 0.25 mol/L sucrose, 2 mmol/L 2mercaptoethanol, 10 mmol/L sodium azide, and 0.1 mmol/L
phenylmethylsulfonyl fluoride with a polytron (4 vol/wt), and
centrifuged at 50 000 g (20 minutes, 4 C). The supernatants
were lyophilized and stored at 20 C. The hs-CRP concentration was determined by Latex particle-enhanced
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Dabidi Roshan et al
193
Table 1. Effect of Exercise Training and Curcumin on CK-MB, hs-CRP, LDL and MDA Levels, as Perilous Biomarkers in Lead-Induced
Myocardial Injury in Rats (Mean + SEM for 7 Rats)
Markers
Groups
Sham
Lead
Trainingþ lead
Curcumin þ lead
Curcuminþ trainingþ lead
CK-MB (U/L)
58.23 +
86.31 +
67.95 +
65.00 +
57.45 +
1.73
3.56a
2.32a,b
1.01a,b
1.30b
HS-CRP (mg/L)
0.0538 +
0.1571 +
0.0788 +
0.0571 +
0.0513 +
0.03
0.09a
0.03
0.04b
0.04b
LDL (mg/dL)
36.57 +
53.85 +
35.28 +
39.28 +
30.85 +
10.62
15.90a
6.40b
10.43b
3.84b
MDA (nmol/g)
26.82
46.08
34.41
35.82
30.36
+ 2.85
+ 9.22a
+ 15.07b
+ 6.49b
+ 12.53b
Abbreviations: CK-MB, creatine kinase-MB; HS-CRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein; MDA, malondialdehyde.
a
Statistical significance P < .05 significantly different than sham group.
b
Statistical significance P < .05 significantly different than lead group.
Immunoturbidimetric assay on a Hitachi 912 automated analyzer
using reagents from Diasorin (Stillwater, Minnesota). The latex
particles coated with antihuman CRP antibody aggregates with
the tissue homogenate CRP, forming immune complexes. The
formed immune complexes caused an increase in turbidity measured at 572 nm, which is proportional to the concentration of
CRP in heart tissue. The high-sensitivity C-reactive protein concentration was determined from CRP standards of known
concentration.11
Biochemical measurements on activity of the GPx enzyme
was conducted using GPx-340 kit (OXIS, Portland, Oregon).
Frozen samples of heart tissue were thawed, rinsed successively
with 0.9% NaCl þ EDTA and with cold 20 mmol/L Tris-HCl,
followed by homogenization. The homogenates were diluted
with cold 20 mmol/L Tris-HCl and centrifuged (10 minutes at
5 C, 3000g). In the supernatants, activity of GPx was estimated
by spectrophotometry. All samples to be statistically compared
were processed in the same assay to avoid interassay variations.
The concentration of lead was detected by means of atomic
absorption spectrophotometry (AAS) method. Lipid peroxidation levels in the tissue homogenate were measured with the
thiobarbituric-acid reaction using the method of Ohkawa
et al.12 The quantification of thiobarbituric acid reactive substances was determined at 532 nm by comparing the absorption
to a standard curve of MDA equivalents generated by acid catalyzed hydrolysis of 1, 1, 3, 3 tetramethoxypropane. The values
of MDA were expressed as nmol/g tissue.
Furthermore, serum CK-MB levels were measured by
immunological DGKE method. Fasting serum high-density
lipoprotein cholesterol (HDL-C) and low-density lipoprotein
cholesterol (LDL-C) concentrations were measured by an
enzymatic colorimetric method, as previously described by
Ademuyiwa et al.13 The assay sensitivity for the 2 tests was
1 mg/dL. Serum TAC was measured using a commercially
available kit (Randox Laboratories, Crumlin, UK) as previously described by Erel et al.14 In this method, the most potent
radical, hydroxyl radical, is produced. First, a ferrous ion solution is mixed with hydrogen peroxide. The sequentially produced radicals such as the brown colored dianisidinyl radical
cations, produced by the hydroxyl radical, are potent radicals.
The antioxidative effect of the sample against the potent free
radical reactions is then measured. The assay has excellent
precision values, which are lower than 3%. The results are
expressed in mmol/mL. In accordance with the protocol of
Sheril et al we analyzed the lead acetate concentration using
a spectrophotometer method only in the lead acetate group.4
Statistical Analysis
Statistical analysis was performed using a commercial software
package (SPSS version 16.0 for Windows). Results are
expressed as means + SE. Data for hs-CRP, CK-MB, and
oxidant/antioxidant markers were normally distributed after
log-transformation. A 1-way analysis of variance (ANOVA)
was used to detect statistical differences between groups.
A post-hoc test (Tukey test) was performed to determine differences in the various markers between groups. The differences
were considered significant at P < .05.
Results
Changes in CK-MB, hs-CRP, LDL, and MDA levels, as biomarkers in lead-induced myocardial injury of animals in each
group, are shown in Table 1. Exposure to lead (20 mg/kg)
caused an increase in the concentration of CK-MB, hs-CRP,
LDL, and MDA by 48%, 192%, 47%, and 71%, respectively,
in comparison to the sham group (all significantly increased
P < .001, P < .05, P < .01, and P < .001, respectively). In contrast, curcumin, exercise training, and both interventions significantly reversed CK-MB, hs-CRP, LDL, and MDA levels (P <
.001, P < .05, P < .01, P < .01, respectively). However, curcumin þ training þ lead treatment was more effective than curcumin þ lead and training þ lead alone treatment.
Changes in the beneficial biomarkers in lead-induced myocardial injury, GPx and TAC, along with HDL in each group
are shown in Table 2. The administration of lead at the concentration of 20 mg/kg for 8 weeks resulted in a decreases in GPx,
TAC, and HDL levels by 43%, 27%, and 26%, respectively, in
comparison to the sham group (P < .001, P < 0.01, and P < .01,
respectively). Conversely, curcumin, exercise training, and
their combination significantly increased GPx, TAC, and HDL
levels (P < .001, P < .01, and P < .01, respectively). However,
curcumin þ training þ lead treatment was more effective than
curcumin þ lead and training þ lead alone treatment (Figure 1).
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International Journal of Toxicology 30(2)
Table 2. Effect of Exercise Training and Curcumin on GPx, TAC, and HDL Levels as Beneficial Biomarkers in Lead-Induced Myocardial Injury in
Rats (Mean + SEM for 7 Rats)
Markers
Groups
GPx (mm of GSH
utilized/ mg protein)
Sham
Lead
Trainingþ lead
Curcuminþ lead
Curcumin þ trainingþ lead
6.4700
3.6757
5.5412
6.2729
7.9500
TAC (mmol/mL)
+ 0.38
+ 0.24a
+ 0.31a,b
+ 0.42b,c
+ 0.43a,b,c,d
385.75 +
279.85 +
411.75 +
411.71 +
450.37 +
8.89
14.33a
13.87a,b
14.37a,b
19.74a,b
HDL (mg/dL)
28.85 +
21.14 +
30.28 +
32.57 +
36.14 +
10.18
5.66
8.95b
7.91b
6.17b
Abbreviations: GPx, glutathione peroxidase; HDL, high-density lipoprotein.
a
Statistical significance P < .05 significantly different than sham group.
b
Statistical significance P < .05 significantly different than lead group.
c
Statistical significance P < .05 significantly different than training þ lead group.
d
Statistical significance P < .05 significantly different than curcumin þ lead group.
Discussion
The present study demonstrates the restorative potential of curcumin and exercise training by reversing lead-induced myocardial damage. Reductions in GPx, TAC, and HDL and increases
in the concentration of hs-CRP, CK-MB, LDL, and MDA indicated deterioration of cardiac function and cellular damage due
to the toxic effects of lead. Oxidative stress results in toxicity
when the rate at which reactive oxygen species (ROS) are
generated exceeds the scavenging capacity of the cell.
Enhancement of MDA and reduction in GPx and TAC suggested oxidative damage in the heart muscle. Treatment by curcumin and exercise training restored lead-induced myocardial
damage and tended to normalize biomarkers, suggesting a
reversal of lead-induced cardiotoxicity, conforming the free
radical scavenging property of curcumin (Tables 1 and 2).
Lead, a commonly-used metal worldwide, has been used
since ancient times. Studies have shown that lead has harmful
effects on several tissues including the nervous system, blood,
the cardiovascular system, and the reproductive and urinary
systems.5 Recent studies suggest that one of the mechanisms
by which lead can exert some of its toxic effects is through the
disruption of the delicate prooxidant/antioxidant balance that
exists within mammalian cells. In vivo studies have suggested
that lead exposure is capable of generating ROS and thus alters
antioxidant defense systems in animals.4 Thus, potential exists
for biological mechanisms linking pollutants such as lead with
cardiovascular disease through inflammation and oxidative
stress.1 In the current study, hs-CRP and CK-MB were assayed
as markers of inflammation and tissue damage in cardiac cells
of rats treated with lead. Results of our investigation revealed a
significant increase in the hs-CRP and CK-MB levels in the
hearts of animals exposed to lead. This suggests that lead acetate had damaging effects on heart tissue during chronic exposure, which may heighten cardiovascular risk.5
The enzyme responsible for the decomposition of lipid peroxides is GPx. This enzyme protects cellular membranes from
peroxidative damage.6 Glutathione peroxidase is a metalloprotein and accomplishes its antioxidant function by
enzymatically detoxifying peroxides.2 Since this antioxidant
enzyme depends on various essential trace elements for proper
molecular structure and enzymatic activity, it is a potential target for lead toxicity.2,3,6 The presence of the free -SH group is
necessary for the proper action of this antioxidant enzyme.
Researchers have shown a decrease in the concentration of the
free -SH groups in the blood as well as in the urine of the rats
exposed to lead.2,6 The decrease in the activity of GPx in the
heart and the increase in MDA concentration in the serum of
the rats exposed to lead can be a result of this heavy metalinduced depletion in the free -SH groups noted in these animals.6 Several studies have shown that lead causes increased
lipid peroxidation and decreased enzymatic and nonenzymatic
antioxdants, which is in agreement with the observations in the
current study.2,3,6
Our data indicate a protective effect of curcumin against
cardiotoxicity. Antioxidant activity of curcumin was reported
by Sharma as early as 1976.15 Curcumin is a known scavenger
of free radicals and can significantly inhibit the generation of
ROS such as superoxide anions, H2O2, and nitrite radical generation by activated macrophages, which play an important role
in inflammation.16 When administered in the current study,
curcumin effectively lowered the hs-CRP, CK-MB, MDA, and
LDL levels after lead exposure, thus protecting cardiac tissues
from inflammation, tissue damage, oxidative stress, and peroxidation lipids. Similarly, an enzymatic component of the
defense system (GPx) was stimulated in the heart by curcumin,
which is in accordance with earlier reports.7,17,18 Manikandan
et al reported that curcumin treatment reduced levels of
xanthine oxidase, superoxide anion, lipid peroxides, and myeloperoxidase while significantly increasing levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GPx), and glutathione-S-transferase (GST) in isoprenalineinduced myocardial ischemia in rats.17 Bharat et al reported
that curcumin downregulated the expression of interleukin
(IL)-6 protein, tumor necrosis factor (TNF), and various other
chemokines, and inhibited the production of IL-8, MIP-1a,
MCP-1, and IL-1a induced by inflammatory stimuli in human
peripheral blood monocytes and alveolar macrophages. In
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Dabidi Roshan et al
195
addition, curcumin downregulates the expression of the NF-kBregulated gene products such as COX-2, TNF, 5-LOX, IL-1, IL6, IL-8, MIP-1a, adhesion molecules, c-reactive protein (CRP),
CXCR-4, and others.19 Thus, curcumin could suppress inflammation through multiple pathways.
Sreejayan et al have suggested that the presence of phenolic
groups in the structure of curcumin are fundamental to explaining its ability to eliminate oxygen-derived free radicals from the
medium largely responsible for the peroxidation of cell lipids.20
The mechanism of protective curcumin is multifactorial,
possibly including (1) its unique conjugated structure, which
includes 2 methoxylated phenols and an enol form of b-diketone,
a structure which shows typical radical-trapping ability as a
chain-breaking antioxidant16,21; (2) prevention of lipid peroxidation and inhibition of ROS generation7; (3) the antioxidant property of curcumin decreases the utilization of vitamin C and
vitamin E in the liver and thus maintains their level8; and (IV)
interactions between curcumin, lead, and metal-curcumin
complex (lead-curcumin); both the hydroxyl groups and the
b-diketone moiety of curcumin are involved in metal-ligand
complexation, either by directly bonding to the metal or by intermolecular hydrogen bonding.4
The current study suggests that supervised endurance training of 8 weeks can potentially produce a significant reduction
in risk of cardiovascular events through decreases in leadinduced elevated levels of hs-CRP, CK-MB, MDA, and LDL,
along with increases in GPx, TAC, and HDL levels. These
results are consistent with those of Frederico et al who reported
that 12 weeks of treadmill training increased antioxidant
enzymes and decreased oxidative damage and injury in the
myocardium through reducing MDA and elevated levels of
CK-MB induced by isoproterenol.22 Researchers have reported
chronic physical activity reduces hs-CRP levels by multiple
mechanisms, including decreases in cytokine production by
adipose tissue, skeletal muscles, endothelial and blood mononuclear cells, and possibly an antioxidant effect.23 Physical
training reduces peripheral inflammatory markers associated
with endothelial dysfunction, such as soluble intracellular and
vascular adhesion molecules, granulocyte-macrophage colonystimulating factor, and macrophage chemoattractant protein-1
in patients with heart failure.24 Regular physical activity also
improves endothelial function preserving nitric oxide availability.25 Although exercise acutely increases oxidative metabolism and thereby induces oxidative stress, there is evidence
that long-term physical activity increases antioxidant defenses
through the upregulation of antioxidant enzymes.26 Furthermore, this antioxidant effect of exercise reduces the susceptibility of LDL to oxidation, which in turn helps further
prevent endothelial injury and inflammation.23
Powers et al reported that training resulted in large and
significant increases in myocardial nonprotein thiols.27 As glutathione is known to be the dominant nonprotein thiol in cells,
endurance training resulted in elevated levels of myocardial
glutathione in the heart. Glutathione plays a pivotal role in the
maintenance of intracellular redox status, antioxidant vitamin
levels (ie, vitamins E and C), and the function of the
antioxidant enzyme GPX. Because GPX requires a supply of
reduced glutathione to remove organic hydroperoxides and
hydrogen peroxide, it follows that a training-induced increase
in myocardial glutathione should result in an improved capacity to remove these potentially injurious metabolites.27 Therefore, it seems that the training-induced increases in both
myocardial enzymatic and nonenzymatic antioxidant systems
are potential mechanisms to explain the training-induced
reduction in myocardial injury.22,27
In summary, we observed that curcumin þ training þ lead
treatment was more effective than curcumin þ lead and training þ lead alone, suggesting a potentially important training
and curcumin interaction. However, there is a lack specific
information with respect to their interaction effects. A large
body of data exist which show that free radicals and ROS
increase cardiovascular risk. Our findings indicate treatment
with curcumin, as a strong antioxidant supplement, can
decrease lipid peroxidation and myocardial damage. Moreover,
curcumin improves total antioxidant capacity in the animal
body. In the long term, regular endurance training could
improve the antioxidant defense systems and injury in the myocardium induced by lead. Treatment with the combination of
curcumin and training could markedly inhibit myocardial damage caused by lead in rats.
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the
authorship and/or publication of this article.
Funding
The author(s) received no financial support for the research and/or
authorship of this article.
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