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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-