T
he
role
of
oxidative
stress
on
the
pathophysiology
of
metabolic
syndrome
R
ev
A
ssoc
M
ed
B
ras
2017; 63(1):85-91
87
products generated from glycation include glyoxal and
methyl glyoxal. These compounds bind to the amino
grouping of amino acids, resulting in advanced glycation
end-products (AGEs) and advanced lipoxidation end-
-products (ALEs),
24
which are highly reactive and participate
in the development of other components of MetS.
Clinical studies in patients with hypertension showed
that systolic and diastolic blood pressure are positively
correlated with biomarkers of oxidative stress and nega-
tively correlated with the levels of antioxidants.
25-27
This
fact is attributed to endothelial dysfunction caused by
oxidative stress and inflammation, producing imbalance
of vasoconstrictor and vasodilator products. This is evi-
denced by an inverse association between factors that
trigger vasodilation, plasma levels of malondialdehyde
and positive association with antioxidants.
28
Oxidative stress plays an important role on the patho-
genesis of insulin resistance by disrupting the release of
adipokines by adipose tissue such as TNF-
α
and IL-6,
which can trigger inflammation, a mechanism already
described above.
29-31
Thus, it seems that obesity and MetS
are factors associated to inflammation and oxidative stress.
A
ntioxidant
defense
Oxidative stress is controlled by the endogenous antioxi-
dant defense system, which includes antioxidant enzymes
such as superoxide dismutase, catalase, glutathione per-
oxidase, glutathione reductase; and nonenzymatic com-
pounds such as ferritin, transferrin, bilirubin, ceruloplas-
min, and even albumin carrier low molecular weight, such
as uric acid and lipoic acid.
32
Exogenous antioxidants from
fruits and vegetables, including hydrophilic as vitamin C
and flavonoids and lipophilic as vitamin E and carotenoids,
are also included. Carotenoids are divided into a group of
pigments that give yellow and orange colors to plants,
animals, and microorganisms. More than 700 carotenoids
have been identified; however, lutein, zeaxanthin, crypto-
xanthin, alpha-carotene, beta-carotene, and lycopene rep-
resent 95% of the carotenoids in human plasma.
33
Antioxidants are able to trap free radicals generated
by cellular metabolism or exogenous sources through the
donation of hydrogen atoms of these molecules, breaking
the chain reaction, which prevents attack on lipids, ami-
no acids in proteins, double bond of the polyunsaturated
fatty acids, and DNA bases, avoiding formation of lesions
and loss of cell integrity.
34
Another role of antioxidants
is the protection mechanism, which acts in the repair of
damage caused by free radicals, a process related to the
removal of the DNA molecule of damage and restoration
of damaged cell membranes.
35
The literature reports that a diet rich in fruits, vege-
tables and grains prevents various diseases, such as car-
diovascular diseases and cancer.
36,37
Other intervening
factor in antioxidant response and the manifestations of
MetS is the association between dietary adequacy and
physical exercise.
38
This is due to the exogenous and en-
dogenous antioxidants acting in synergy in combating
free radicals.
25
However, it is important to note that this
intake needs to be steady and orderly and that the intake
of vitamins in supplement formmay result in pro-oxidant
effects called stress antioxidative.
39
B
iomarkers
of
oxidative
stress
The reactive species are very unstable and have a very short
half-life, which makes it a major challenge to perform an
accurate assessment of these species. For this reason, meth-
ods have been developed for measuring products resulting
from the redox markers in biological samples, which are
oxidation products of lipids, DNA and proteins.
40
Among
the most common are the products of lipid peroxidation
because of polyunsaturated fatty acids (such as phospho-
lipids and glycolipids). When these lipids are oxidized, two
products classically measured in biological samples, malo-
ndialdehyde (MDA) and isoprostan, are formed.
40,41
MDA is formed by the peroxidation of polyunsatu-
rated fatty acids and can interact with proteins. MDA can
be detected by the thiobarbituric acid (TBA) using a
colorimetric method based on MDA TBA reaction and
form a pink color, so gauging MDA and all species react-
ing with this acid.
42
The MDA can be specifically measured
by high performance liquid chromatography (HPLC). The
same reaction occurs between MDA and TBA, but due to
the apparatus of the fluorescence detector, only the MDA
is identified, making this more specific test.
43
The isoprostane is a stable product of lipid peroxida-
tion, and can be measured both in the tissues and in bio-
logical fluids including urine, plasma, and cerebrospinal
fluid. The level of this compound in plasma and urine
correlates with the levels of reactive oxygen species and
oxidative stress in experimental studies in humans.
44
However, in healthy individuals at risk for obesity and
hyperlipidemia their levels are increased, suggesting it as
a good marker for cardiovascular risk.
41
Total antioxidant capacity can be considered a mark-
er of oxidative stress, since it measures the state of anti-
oxidant capacity in biological fluids. This method gives
deeper insight into the involvement of oxidative stress in
several pathophysiological conditions, but also monitors
the effectiveness of antioxidant interventions.
44
In this
method the antioxidant capacity of the sample is quanti-