Lupine Publishers | Journal of Urology & Nephrology
Introduction
Oxidative stress is one of the most common pathological processes,
the essence of which is an imbalance in the state of the pro- and
antioxidant systems of the blood, organs and tissues. This indicates the
need for its direct pathogenetic correction, which can be carried out
by means of specific and non-specific antioxidant therapy.
Oxidative stress (OS) is a state in which the amount of free radicals
generated in the body significantly exceeds the activity of endogenous
antioxidant systems that ensure their elimination [1,2].The imbalance
between the synthesis and elimination of reactive oxygen forms, affects
the homeostasis of cellular oxidative stress, plays an important role in
the development of a number of cardiovascular diseases (CVD) in the
pathogenesis, including arterial hypertension, hypercholesterolemia,
atherosclerosis, diabetes mellitus and heart failure [3-5].
Reactive oxygen species (ROS) are initially normal components of
cellular metabolism and perform essential regulatory and metabolic
functions in the body. Free radical reactions are necessary for the
formation of many vital enzymes, as well as for the normal function of
the immune system and its components. Sharp fluctuations in their
concentration in cells and tissues can cause many pathological
conditions in the body.
The formation of OS, due to increased formation of ROS, especially
superoxide anion (O-2) and insufficient mechanisms of antioxidant
protection indicates the development of functional and structural
disorders of the cardiovascular system. The main characteristic of CVD
disorder in the vascular wall is endothelial dysfunction. In vascular
cells, a superoxide anion is formed from ROS, which is inactivated by
superoxide dismutase (SOD).
Endothelial dysfunction is caused not by a decrease in nitric oxide (NO)
production, but by excessive O-2 formation, which leads to oxidative
inactivation of NO and a decrease in its bioavailability.
In addition, O-2, directly or through the product of its interaction
with NO (peroxynitrite), is capable of initiating peroxide damage to the
cellular and matrix elements of the vessel wall, leading to disruption
of the interaction of the endothelium with cellular elements and blood
lipoproteins.
These data indicate that the production of superoxide radicals and other
forms of oxygen, uncontrolled by physiological antioxidant enzymes, can
be considered as a potential source of vascular dysfunctions, a
frequent manifestation of which is endothelial dysfunction.It has been
established that both stable high and periodically increased glucose
levels induce the development of OS, which, in turn, stimulates
apoptosis of endotheliocytes [6].
Direct determination of the level of oxidants under in vivo conditions
is practically impossible, since these are extremely reactive and,
therefore, short-lived compounds. Ideal OS markers are oxidation
products of lipids, carbohydrates, proteins, and nucleic acids, whose
lifespan ranges from several hours to several weeks.8-iso-PgF2a
(8-isoprostane) is considered to be one of the most specific biological
markers that allow one to assess the level of free radical production
with a sufficient degree of accuracy, reliability and reproduction of
research results.
8-isoprostane is a metabolic product in the reactions of peroxidation of
arachidonic acid, isomeric prostaglandin F2 and its amount is directly
proportional to the level of formed free radicals [7].OS is one of the
links in the formation of pathogenetic changes in the body [8]. An
increase in OS and a decrease in antioxidant protection lead to
mitochondrial DNA damage and depletion of
adenosine triphosphate [9]. Today, the role of oxidative stress in
the development of endothelial dysfunction has been proven [10].
Molecules formed by oxidation can serve as biomarkers. Their
analysis is used to quantify oxidative stress in humans.Biomarkers of
mitochondrial dysfunction and oxidative stress are:-8-isoprostane,
malonic dialdehyde; O-tyrosine, 3-chlorothyrosine, 3-nitrotyrosine;
protein oxidation products (AOPP);8-hydroxyguanosine (8-OHG);
8-hydroxy-2’-deoxyguanosine (8-OHdG); cellular mtDNA (its
number and the presence of mutated variants with deletions);
endogenous antioxidants (glutathione, cysteine, uric acid,
ubiquinol) [11].
Comprehensive assessment of OS, expensive research,
infrequent use and relatively long-term implementation, makes this
research method limited. It should be noted that not every medical
institution can allow the use of the OS assessment research method.
The need to find a method for evaluating OS that differs in prostate
availability has become relevant at the present time.
In connection with the above, it is of interest to use, as an
estimate and a potential regulator of the balance between the
synthesis and elimination of ROS, infrared radiation of the far
range (IRR FR), which includes electromagnetic oscillations with
wavelengths from 1 to 10 mm [12]. One of the main properties of
IRR FR is the dependence of the results of exposure on the phase of
biological development and on the initial state of the object: the IRR
FR practically does not affect the normal functioning of a healthy
organism [12-14], and in the event of a pathology, it can regulate
its functioning within the limits inherent in this biological kind
[15,16].
ROS have a molecular spectrum of radiation and absorption of
IRR FR (wavelength 10-2-10-4 m; frequency 1011-1013 Hz) [17].
It was found that the reactivity of molecules excited by an IRR FR
quantum will be an order of magnitude higher than when excited
by an extremely high frequency electromagnetic radiation quantum
[18].
Purpose of research
To assess OS and the relationship with paradoxical vasoconstriction of the cavernous arteries.
Materials and Methods
17 men with CVD and cardiovascular risk factors aged 35 to 65
years (mean age 51.3 ± 1.33 years) were examined in a hospital.
The control group consisted of 7 men without CVD and risk factors.
Blood for biochemical, enzyme-linked immunosorbent assay was
taken in the morning on an empty stomach, the next day after the
patient was admitted to the hospital, 12 hours after eating. Blood
sampling was performed from the cubital vein. The criteria for
excluding patients from the study were concomitant inflammatory endocrine and other diseases that could affect the activity of
oxidative processes. Overweight was assessed using the body mass
index (Quetelet index), which is defined as the ratio of body weight
(kg) to the square of height (m).
According to modern data, 8-isoprostane (8-PI) is considered
to be one of the most specific markers that allow, with a sufficient
degree of accuracy, reliability and reproducibility of research
results, to assess the level of production of free radicals in the
body in a wide variety of pathologies. It is a metabolic product
in the reactions of peroxidation of arachidonic acid, isomeric to
prostaglandin F2α (PGF 2α). It belongs to the family of eicosanoids,
the formation of which occurs during non-enzymatic (free radical)
oxidation of phospholipids of cell membranes [9,10]. Its content in
blood serum was determined by the enzyme immunoassay using
the 8isoprostane ELISA kit from USBiological (USA). The data
obtained were expressed in pg/ml.
All men underwent a comprehensive examination, which
included the collection of a general medical and sexological history,
a general examination, a study of hormonal status, lipid spectrum
and blood glucose. All patients underwent a questionnaire survey
the International Index of Erectile Function (IIEF-5).In addition, all
men underwent a study of the endothelial function of the cavernous
arteries, using the method of ultrasound examination of changes
in diameter after exposure to narrow-spectrum (far range) IR
emitters.
The Percentage Increase in the Diameter of the Cavernous
Arteries (PIDCA) was calculated by the formula:
Formula 1.
PIDCA = 100% x (D 2 –D 1) \D1.
Where D1 is the average diameter of both cavernous arteries
before irradiation with an IR emitter.
D2 - the average diameter of both cavernous arteries after
irradiation.
The threshold value of PIDCA for identification of arteriogenic
ED from other forms of ED was 30%. PIDCA <0% was regarded as
paradoxical vasoconstriction.
Results and Discussion
The content of 8-isoprostane and the endothelial function of the
cavernous arteries in the examined men of 2 groups are presented
in Table 1.
As you can see from the Table 1, the patients of the main group
showed an increase in the content of 8-isoprostane in the blood
serum by 14.1 times as compared with the control group. PIDCA
characterizing endothelial function was within the normal range in
men of the control group. In patients of the main group, endothelial
dysfunction was revealed, and in 82.3% (n=14) cases, paradoxical
vasoconstriction of the cavernous arteries was recorded (PIDCA
<0%). Only in 3 patients (17.6%) the endothelial function of the
cavernous arteries was recorded as positive. However, these
indicators were below normal, which indicated the presence of
endothelial dysfunction.
Table 1:Indicators of 8-isoprostate and PIDCA in the examined patients.
Note: * Significant differences compared with the control group Р <0,05.
Correlation analysis between the OS biomarker (8-isoprostane)
and paradoxical vasoconstriction of the cavernous arteries in
patients with CVD and cardiovascular risk factors showed a
negative relationship (r = -0.365; p = 0.043).
Of the surveyed men in the main group, 23.5% were
overweight; 76.4% were obese. Type II diabetes mellitus affected
5 (29.4%) men; hypercholesterolemia/dyslipidemia was detected
in 94.1% (16) patients; active smokers were 7 (41.2%) patients.
When analyzing the IIEF-5 questionnaires of the main group, it was
found that the severity of ED was as follows: mild in 5 (29.4%) men,
moderate in 10 (58.8%) patients, and severe in 2 (11.8%).
Thus, the data obtained indicate an increase in the activity of
8-IP in the blood serum, which is interpreted as the formation of
oxidative stress in CVD and cardiovascular risk factors (obesity,
smoking). These indicators correlate with literature data [19-21].
The study of the 8-IP level is the gold standard for determining
the OS activity in persons with CVD, as well as in patients with
diabetes mellitus, obesity, hypercholesterolemia, and smokers
[22].OS forms the development of endothelial dysfunction, the
manifestation of which can be a predictor of dangerous vascular
disease, and, therefore, can be used as a screening assessment for
men after 35 years.
The manifestation of endothelial dysfunction can be both
disturbances in the normal blood flow in the penis (decrease
or disappearance of spontaneous and adequate erections), and
disturbances in the coronary circulation system. Violation of
blood flow can manifest itself as erectile dysfunction, and as
atherosclerotic coronary artery disease. Erectile dysfunction is
a manifestation of endothelial dysfunction without intermediate
stages, while atherosclerosis of the coronary arteries most often
develops asymptomatically for a long time and manifests as acute
coronary syndrome and ischemic heart disease.
The OS, being a systemic process, first of all subjects the
vascular endothelium to functional changes, spreading from the
“periphery to the center”, that is, from the capillaries to the large
main or organ vessels.
The mechanism of paradoxical vasoconstriction of the
cavernous arteries can be explained as follows. Under the influence
of IRR FR, with a frequency corresponding to the molecular
spectra of emission and absorption of NO and ROS, phagocytes
(monocytes) of blood and endotheliocytes are activated. This leads
to the release of NO and ROS, which increases the oxidative stress of
the endothelium. In addition, excess NO can bind with superoxide
radicals to form the strongest oxidizing agent, peroxynitrite. This
leads to endothelial dysfunction, ATP depletion, and increased
production of the vasoconstrictor endothelin 1.
Conclusion
Paradoxical vasoconstriction of the cavernous arteries is a manifestation of systemic oxidative stress at the level of regional circulation. The use of long-range infrared radiation in the diagnosis of endothelial dysfunction of the cavernous arteries can also be used to determine the severity of oxidative stress. The use of IRR FR in diagnostics of the system OS has unconditional advantages - these are non-invasiveness, simplicity and speed of execution, the possibility of repeated use, and most importantly, it is economically uncomplicated and beneficial.
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