Research Article
Effect of Aerobic Training Program on Serum C-reactive Protein Levels
Mojtaba Eizadi 1, Shahram Sohaily 2 * , Davood Khorshidi 3, Hamidreza Samarikhalaj 3
1 Department of Physical Education and Sport Sciences, Islamshahr Branch, Islamic Azad Uniersity, Tehran, IR Iran
2 Department of Physical Education and Sport Sciences, Islamic Azad University, Shahr-e-Qods Branch, Tehran, IR Iran
3 Department of Physical Education and Sport Sciences, Islamic Azad University, Saveh Branch, Saveh, IR Iran
*Corresponding
author: Shahram Sohaily, Department of Physical Education and Sport
Sciences, Islamic Azad University, Shahr-e-Qods Branch, Tehran, IR Iran.
Tel: +98-9193551960, Email: shahramsohaily@yahoo.com
Abstract
Background: Smoking is an established risk factor for cardiovascular diseases and metabolic syndrome.
Objectives: Here
we aimed to assess the effect of 3-month aerobic training on C-reactive
protein (CRP) level and total antioxidant capacity (TAC) in male
smokers.
Patients and Methods: A
total of 34 male cigarette smokers aged 35 – 45 years participated in
this study by accessible sampling and were divided randomly into
experimental and control groups. Pre- and post-training CRP and TAC data
were collected in both groups and compared by Student’s t-test.
Results: Aerobic training resulted in a significantly increased TAC (P < 0.001), but CRP remained unchanged (P = 0.96).
Conclusions: Despite a lack of CRP change, long-term aerobic training is associated with anti-oxidative effects.
Keywords: Aerobic Training; Smoking; Stress Oxidative; Inflammation
1. Background
The oxidative stress
condition that follows an increased production of reactive oxygen
species or free radicals in response to smoking is associated with
symptoms such as stimulation of DNA breakage, inactivation of specific
proteins, and breakage of biological membranes (1).
In smokers, the antioxidant defense capability, or total antioxidant
capacity (TAC), against free radicals and other oxidants is reduced. In
fact, increased oxidative stress, as a consequence of reduced defense
capacity or capability of antioxidants in the immune system against the
increased oxidants, plays a significant role in the pathogenesis of
smoking-related diseases such as cancer, cardiovascular diseases,
metabolic syndrome, hypertension, and type 2 diabetes (2). The literature supports the role of oxidative stress in the pathogenesis of 100 different diseases (3).
Studies show that the lung epithelial cells are the primary targets of
the inflammatory damage caused by smoking. Cigarettes are known to
contain > 4,700 chemicals and oxidants (4),
which comprises an important etiological factor in the development and
severity of respiratory diseases such as chronic obstructive pulmonary
disease (COPD).
Activated inflammatory cells secrete and produce various
inflammatory mediators in response to smoking; among them, inflammatory
cytokines are the most important. Some recent studies have identified
the correlation between smoking and increased inflammatory biomarkers
such as C-reactive protein (CRP), fibrinogen, and increased numbers of
white blood cells and other inflammatory cytokines such as interleukin
(IL)-6 (5).
Changes in the levels of such inflammatory cytokines not only occur in
smokers’ lungs and airways but also in their circulation (6).
In this regard, one study showed that the serum CRP levels of smokers were significantly higher than those of non-smokers (7).
Its connection to the surface of microorganisms activates the
complement pathway as part of the immunological response, which
subsequently creates a primary defense mechanism against infection and
protects active tissue in the body against toxins. However, its
increased serum or plasma levels increased inflammation in smokers,
stressing the harmful effects of cigarette smoking on the immune system (8).
Researchers also suggested that increased CRP levels in smokers
compared to non-smokers increases the risk of atherosclerosis (9).
Smoking has also been shown to cause oxidative stress and dysfunction
in the inflammation profile in the airways and alveolar epithelium, both
of which are important in the pathogenesis of smoking-related diseases (10).
Thus, understanding the mechanisms responsible for the effects of
smoking on the inflammatory profile as well as oxidant and antioxidant
levels has been the focus of health scientists. In this respect,
although studies on the responses of CRP or oxidative stress indexes are
limited to a variety of exercise trainings, findings in other healthy
or patient populations are also more or less contradictory and
inconsistent, as some studies showed beneficial effects (11-13), whereas others showed ineffectiveness (14-16) of exercise on the TAC or CRP levels of healthy or patient populations.
2. Objectives
Given the contradictory
findings in other populations as well as the limited studies on smokers
in the field, this study aimed to determine the effect of 3 months of
aerobic exercise on serum CRP levels and TAC in male smokers. We also
queried whether changes in CRP in response to training are associated
with changes in TAC. Obtaining the answer to this question is also a
main objective of the present study.
3. Patients and Methods
In this
quasi-experimental study, the effects of 3 months of aerobic exercise on
serum CRP levels and TAC were measured in male smokers with a sedentary
lifestyle. The study population consisted of 36 male smokers aged 35 –
45 years in Saveh who were randomly divided into the experimental
(participation in aerobic training for 3 months) and control (no
exercise) groups. After being informed by the researchers of the study
objectives, consent forms were completed and signed by the participants.
3.1. Inclusion and Exclusion Criteria
Smoking at least 10 cigarettes a day for at least 3 years was the smoking criterion (17).
The studied subjects were non-athletes, meaning that during the last 6
months, they had not participated in any regular exercise. Their weight
had not fluctuated more than 1 kilogram in the preceding 6 months. A
history of metabolic or chronic inflammatory disorders such as type 2
diabetes, asthma, cancer, and cardiovascular or liver disease was the
health-related exclusion criterion.
3.2. Measurements of Anthropometric Indices
Anthropometric indices and body fat percentages were measured at
the study start and end. Heights were measured using a wall stadiometer
after the subjects removed their shoes with an accuracy of 0.1 cm. Body
mass index (BMI) was calculated by dividing weight in kilograms by the
height in meters squared. Body fat percentage was measured by a body
composition measurement device (HFB590; Omrun, Finland). Waist and hip
circumferences were measured in the thickest area using an inelastic
tape measure. Abdominal to hip circumference ratio (AHR) was calculated
by dividing waist circumference by hip circumference.
3.3. Measurement of Clinical Markers Training Protocol
Blood samples were obtained in the fasting condition before
exercise program and 48 hours after the last training session. Subjects
were asked to be present in the laboratory between 8 and 9 am after an
overnight fast (10 – 12 hours). Subjects were prohibited from
participating in any physical activity for 48 hours before the blood
samples were drawn. After each subject entered the lab and rested for 20
minutes, venous blood samples were collected via the cannulated
antecubital vein. Serum isolation was performed immediately thereafter,
and the samples were stored at -76°C until use. CRP levels were measured
by enzyme-linked immunosorbent assay (High-Sensitivity CRP [Hs-CRP]
ELISA; Diagnostics Biochem Canada Inc.). The Hs-CRP assay sensitivity
was 10 ng/mL, while the intra- and inter-assay coefficients of variation
were 5.0 and 9.5%, respectively. Plasma TAC was measured by the FRAP
assay.
The aerobic exercise training was conducted in 45- to
60-minute sessions three times a week for 3 months at each subject’s 60%
- 80% maximum heart rate. The first session had the least duration and
intensity, while the duration and intensity increased as the last
session was approached. Each session started with a warm-up phase
followed by continued aerobic activities in the form of running on a
flat surface and group aerobic exercise and ended with cooling down.
Target heart rate was controlled and recorded using a heart pulse meter
(POLAR, Finland) (18).
3.4. Statistical Analysis
The statistical analysis was conducted in SPSS 15. The
Kolmogorov–Smirnov test was used to determine the data distribution. The
independent t-test was used to compare the pre-tests between the
experimental and control groups. The paired t-test was used to determine
the significance level of the differences of each pre- versus post-test
variable value. The correlation between serum CRP level and TAC was
determined using the Pearson correlation test. Values of α < 0.05
were considered significant.
4. Results
Here we investigated the
effect of 3 months of aerobic training on serum CRP and TAC in male
smokers. Pearson correlation data showed a significant inverse
correlation between serum CRP and TAC at baseline (P = 0.001, r = -0.55;
Figure 1). The patterns of these two variables (Figure 1) show that a reduced serum CRP level was associated with increased TAC in the studied smokers.
|
Figure 1.
The correlation
between total antioxidant capacity and C-reactive protein patterns in
the studied male smokers is significant and inverse.
|
The pre- and post-training of physical characteristics and clinical variables of the two groups are shown in Table 1.
Based on the independent t-test, no significant difference was observed
in any anthropometrical marker between the two groups at baseline (P
> 0.05). There were no statistically significant differences between
the exercise and control groups with regard to TAC at baseline (P =
0.92). No significant difference was also found in serum CRP between two
groups at baseline (P = 0.96).
|
Table 1.
Mean and Standard Deviation of Anthropometrical and Clinical Characteristics in Pre- and Post-Training of the two Study Groupsa
|
According to the paired sample t-test findings, the aerobic
training program resulted in a significant decrease in all
anthropometrical markers, including weight, AHR, BMI, and body fat
percentage compared with pre training (P < 0.001).
The effect of aerobic training on serum CRP and TAC in smoker
men were main aims of present study. Compared to pre-training, TAC
increased significantly after exercise program (P = 0.001) but this
clinical variables was not changed in control subjects. On the other
hand, serum CRP did not change with aerobic training program in exercise
group (P = 0.96).
5. Discussion
In this study, aerobic
exercise significantly increased the TAC in male adult smokers but serum
CRP levels did not change significantly. However, a significant
correlation was observed between changes in TAC and those in CRP levels
in response to training, which is clinically interesting.
Oxidative stress plays an important role in the pathogenesis of
many diseases, including COPD, lung cancer, and atherosclerosis.
Cigarette smoke also increases oxidative stress by producing reactive
oxygen radicals and reducing the body’s antioxidant defense system. This
also leads to chronic diseases such as type 2 diabetes, hypertension,
and metabolic syndrome as well as malignant diseases (19).
It was once believed that the ability and role of smoking in
producing oxidative stress in the alveolar epithelial cells are not
associated with the release of pro-inflammatory cytokines (20).
These studies even reported the ineffectiveness of smoking on the
release of pro-inflammatory cytokines in airway cells. However, more
recent studies have pointed out to the close association between
pro-inflammatory cytokines and oxidative stress or antioxidants (21).
Researchers believe that oxidative stress caused by smoking leads to
the destruction of alveolar walls and airway resistance. On the other
hand, increased oxidative stress results in the impairment and increase
in the pro-inflammatory cytokines in the lungs of smokers and COPD
patients (22).
In this respect, the findings of this study showed the significant
negative correlation between TAC and serum CRP level as a
pro-inflammatory cytokine, which supports the close correlation between
oxidative stress and inflammatory profile in smokers.
The literature has revealed that the epithelium of the airways
and the upper parts of the lungs is the main target of the inhalants
that play an important role in the release of pro-inflammatory
mediators. This release plays an important role in the development of
tissue damage during inflammatory processes or inflammatory diseases,
representing or reflecting the role of the epithelium in the airways or
lungs in the pathogenesis of inflammatory respiratory diseases such as
COPD (10).
Laboratory findings in previous studies revealed that smoking increases
the release of pro-inflammatory cytokines in the lungs of smokers and
tobacco chewers (23).
However, the precise molecular mechanisms by which cigarettes affect
the release of pro-inflammatory cytokines, particularly in the alveolar
cells or airways, are not yet fully understood. Previous studies have
shown that the toxic effects of cigarettes (24) occur mainly due to their chemical components, such as acrolein, nicotine, benzopyrene, and N-nitrosamines (25).
On the other hand, these findings clearly show that smoking is toxic to
the alveolar cells and plays a role in the development of
smoking-related lung diseases (24).
Despite the limited availability of studies on the response of
antioxidants or antioxidants as well as inflammatory mediators to
exercise in smokers, in this study, 3 months of aerobic training
significantly increased the TAC in adult male smokers who previously led
an inactive lifestyle. This finding indirectly supports the reduced
intensity of oxidative stress in smokers in response to long-term
exercise training. Improved TAC along with reduced oxidative damage
induced by training has also been reported by other studies (26).
However, in a recent study, despite a significant increase in
superoxide dismutase activity and reduced malondialdehyde level
following 8 weeks of progressive resistance training in male
non-athletes, glutathione peroxidase activity and TAC were not
significantly changed (27).
In addition to training type and measurement tool, the inconsistencies
in these findings appear related to differences in the studied
populations since most studies that reported unchanged levels of
oxidants or antioxidants in response to physical activity were performed
in healthy athletes or non-athletes (26, 27).
However, not all of those studies of patient populations or those
somehow influenced by external stimuli suggested improved antioxidant
capacity or oxidative stress (12, 13).
Overall, antioxidant supplementation to increase the internal
antioxidant capacity reduces exercise-induced reactive oxygen species (28).
A significant increase in the TAC in male smokers in response
to training was observed, whereas serum CRP levels were not affected.
However, a significant correlation between serum CRP level and TAC was
observed before the exercise training. In fact, the finding of an
unchanged CRP level despite significant TAC improvement is somewhat
controversial. However, some studies have reported the ineffectiveness
of long-term exercise training on CRP level in other healthy or patient
populations. For example, in a recent study, 3-month-long exercise was
not associated with changes in inflammatory markers such as CRP in
patients with chronic heart disease (14).
In another study, 6 months of aerobic exercise significantly changed
the levels of inflammatory markers such as CRP, IL-6, and tumor necrosis
factor-α in postmenopausal obese or overweight women (29). In contrast, in two other studies, exercise training in the form of 24 weeks of fast walking 5 times a week (11) and 3 and 6 months of intensive aerobic and resistance exercise (30)
significantly reduced the serum CRP levels and cardiovascular risk
factors in patients with multiple sclerosis or inflammatory rheumatic
disorder. In another study, 3 months of moderate aerobic exercise led to
improvements in the oxidative stress reagents such as superoxide
dismutase and inflammatory profile and decreased insulin resistance in
obese men (31).
However, the unchanged CRP level despite significant TAC
improvement through aerobic exercise remains controversial. It is also
possible that serum CRP in response to training or other interventions
such as quitting smoking has a delayed response or requires a long
period of time. Most studies that have measured CRP levels in smokers
have reported a lack of reduction in its levels immediately after
quitting, which suggests the involvement of deep tissue damage caused by
smoking and the long-term recovery required (6).
In this regard, a longitudinal study reported higher CRP levels in
smokers than in non-smokers. It also showed that even 5 years after
smoking cessation, the difference is still significant, and full
recovery to or normal CRP levels have been reported in those who have
not smoked in 20 years (32). In that study, after not smoking for 30 – 55 years, CRP levels decreased from 1.92 mg/L in the initial state to 1.25 mg/L (32).
According to the findings of this study, although exercise
training is associated with increased TAC and insignificant changes in
serum CRP levels, it does not affect serum CRP level as an inflammatory
cytokine in male smokers. However, a clinically important inverse
correlation was observed between their changes in response to exercise
training. These findings somehow support the fact that reduced oxidative
stress or increased TAC is associated with an improved inflammatory
profile. Further studies with larger sample sizes that measure other
oxidant and antioxidant agents are recommended to confirm our findings.
Acknowledgments
We express our gratitude to all of the study
participants. We thank the Research Deputy of Islamic Azad University,
Islamshahr Branch, for the financial support of and cooperation in
implementing this project.
Footnotes
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