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Свекатун Вячеслав Миколайович асистент кафедри дитячих хвороб Запоргзький державний медичний ^верситет, м. Запорiжжя, Украша
ORCID: 0000-0001-8880-7316 DOI: 10.24412/2520-6990-2022-27150-14-17 ВИКОРИСТАНЯ МАРКЕР1В ОКСИДАТИВНОГО СТРЕСУ ТА СТАНУ АНТИОКСИДАНТНО1 СИСТЕМИ В ПРОГНОЗУВАНН1 ТЕЧП ПЕРВИННОГО ОБСТРУКТИВНОГО МЕГАУРЕТЕРА У
Д1ТЕЙ
Svekatun Vyacheslav Nikolaevich
assistant of the Department of Children's Diseases Zaporizhzhia State Medical University, Zaporizhzhia, Ukraine
THE USE OF OXIDATIVE STRESS MARKERS AND THE STATE OF THE ANTIOXIDANT
SYSTEM IN PREDICTING THE FLOW OF PRIMARY OBSTRUCTIVE MEGAURETER IN
CHILDREN
Анотацш
У статтi наведено результати порiвняльного до^дження маркерiв окисног деструкцИ бшюв (рiвень А ФГ та КФГ) та метаболiтiв оксиду азоту (показники NO та NOS) в сироватцi кровi дiтей хворих на первинний обструктивний мегауретер та дiтей без наявностi обструкцИ сечовивiдних шляхiв. Дослi-дження груп хворих пролжованих ендоскотчним л^ванням або вiдкритим оперативним методом проведено до, та через 3-6 мкящв тсля вiдновлення уродинамки.
Abstract
The article presents the results of a comparative study of markers of oxidative destruction ofproteins (APH and KPH levels) and nitric oxide metabolites (NO and NOS indicators) in the blood serum of children with primary obstructive megaureter and children without urinary tract obstruction. The study of groups of patients treated with endoscopic treatment or open surgery was conducted before and 3-6 months after the restoration of urodynamics.
Ключовг слова: обструктивний мегауретер, маркери оксидативного стресу та стану антиоксидан-тно'1 системи, альдегiдфенiлгiдразони, кетонфенiлгiдразони, монооксид азоту, синтаза оксиду азоту, дти.
Key words: obstructive megaureter, markers of oxidative stress and the state of the antioxidant system, alde-hyde-phenylhydrazone, ketone-phenylhydrazone, nitrogen monoxide, nitric oxide synthase, children.
Introduction.
Insufficient coverage in the world literature of issues of differential diagnosis of organic and functional causes of ureteral dilatation in children of the younger age group and the lack of a generally accepted algorithm for the management of patients with primary obstructive megaureter served as the purpose of this study [6, 8, 12].
Thus, to assess the degree of neurodestruction of the organs of the urinary system in children, we used markers of oxidative stress and the state of the antioxi-dant system, which were determined in blood serum during a biochemical study (concentrations of nitrogen monoxide, NO synthase, aldehyde-phenylhydrazones and ketone-phenylhydrazones). That is, based on the level of these products, conclusions were made about the minimal intensity of oxidative stress in neurons, glial cells, and subcellular structures [2, 7].
The determination of the concentration of the inhibitor of markers of oxidative stress and the state of the antioxidant system, namely: the concentration of nitric oxide, NO-synthase, aldehyde-phenylhydrazones and ketone-phenylhydrazones was carried out in the blood serum obtained after centrifugation of fresh venous blood.
Relevance. At present, the diagnosis of primary obstructive megaureter is mainly based on ultrasound examination, excretory urography, voiding cystourethrography [9, 11, 12]. But an important question remains the evaluation of the effectiveness of treatment of megaureter in children, in which it is important to correctly interpret not only renal urodynamics, but also changes in the functional state of the entire urinary system in the dynamics of treatment, detecting the development of nephrosclerotic signs in advance [11].
Objective.
The development of clinical and laboratory methods of diagnostics, which allow to differentiate damage to urodynamics of a functional or organic nature, to determine the tactics of managing patients with obstructive uropathy.
Materials and methods.
Research was conducted on the content of APH, KPH, NO, NOS in the blood serum of 130 children aged 1 to 48 months: 15 - the main group, 28 - the control group, and 87 - the reference group. 3 groups of children were selected: 1) 15 children of the main group who underwent endoscopic treatment; 2) 28 children of the control group, treated by an open surgical method;
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and 3) 87 children of the reference group - without obstruction of the urinary tract. Examinations of children in the primary and control classes were carried out before and after operative restoration of urodynamics. By gender and age, the studied groups did not differ significantly (p<0.05).
Results.
Research on the products of protein peroxidation, aldehyde-phenylhydrazones and ketone-phenylhydra-zones, by the method of B. Halliwell [2] showed the following results. The average level of APH in children of the reference group was 2.55 ± 1.34 conventional unit of gram protein (c.u.g/p), the average level of KPH was 1.57± 0.89 (c.u.g/p). The analysis of changes in the level of markers of the state of the antioxidant system APH and KPH in the serum of children with primary obstructive megaureter showed the following results:
Table 1
Concentration of APH and KPH (c.u.g/b) in serotype children of the reference group and ailments on the
- in the children of the main group: the average level of APH 2.57 ± 0.58 (c.u.g/p), KPH 1.9 ± 0.44 (c.u.g/p);
- in the children of the control group: the average level of APH 2.84 ± 1.15 (c.u.g/p), KPH 1.91 ± 0.73 (c.u.g/p).
Thus, the average level of KPH in both groups of children with primary obstructive megaureter before treatment was almost 15% higher than the level of the reference group. The level of APH in the children of the main group was almost within the normal range, while in the children of the control group, an increase in its indicators was noted.
The data of APH and KPH indicators in blood serum of children of the reference group and children with primary obstructive megaureter are presented in the table 1.
№ Groups of examinees APH (c.u.g/p) KPH (c.u.g/p)
1 The main group (n=15) 2,57 ± 0,58 * 1,9 ± 0,44 *
2 The control group (n=28) 2,84 ± 1,15 * 1,91 ± 0,73 *
3 The reference group (n=87) 2,55 ± 1,34 ** 1,57± 0,89 **
* - p < 0,001; ** - p < 0,01.
The study of nitric oxide metabolites as markers of oxidative stress - nitric oxide (NO) and NO-synthase (NOS) - showed that in the blood serum of children of the reference group who do not have congenital urolog-ical pathology and diseases of the kidneys and urinary tract, the activity of NO was equal to 3, 32 ± 2.03 c.u.g/p, the root mean square deviation (c) was 2.04, and the limits of variation for NO ranged from 0.33 to 8.62.
Table 2
Nitrogen monoxide (NO) and NO-synthase (NOS) concentration (c.u.g/p) in blood serum of children of the
reference group and patients with megaureter.
The average activity of NOS was 9.75 ± 2.23 c.u.g/p, c = 3.38, the limits of control fluctuations for the levels of NOS activity - from 3.31 to 18.25.
Data on NO and NOS indicators in blood serum of children of the reference group and patients with primary obstructive megaureter of children before surgical correction of urodynamics are presented in Table 2.
№ Groups of examinees NO (c.u.g/p) NOS (c.u.g/p)
1 The main group (n=15) 3,89 ± 2,23* 7,78 ± 3,9**
2 The control group (n=28) 3,43± 2,07* 7,43 ± 3,73**
3 The reference group (n=87) 3,32 ± 2,03** 9,75± 3,38*
* - p < 0,001; ** - p < 0,01.
Further analysis of nitric oxide metabolites (NO and NOS) in the serum of children 3-6 months after the correction of urodynamics, the following results were established. Yes, after treatment, the NO serum concentration has decreased: in 8 (53.33%) children of the main group; in 17 (60.71%) children of the control group.
The concentration of NOS in the serum increased: in 7 (46.66%) children of the main group; in 15 (53.57%) children of the control group.
Concentrations in blood serum remained unchanged in the postoperative period: NO - in 3 (6.97%) and NOS - in 3 (6.97%) children. Deterioration of the level of NO indicators after treatment occurred in 15 (34.88%), NOS - in 18 (41.86%) patients.
That is, it can be assumed that in this part of patients, urodynamic disorders were so significant that
surgical correction did not lead to significant normalization of the urinary tract function. Therefore, determining the levels of nitric oxide metabolites (NO and NOS) as markers of oxidative stress are informative indicators of damage to the organs of the urinary system, which should be used as indicators of the effectiveness of correction of primary obstructive megaureter in children.
The analysis of aldehyde-phenylhydrazones and ketone-phenylhydrazones as indicators of oxidative destruction of proteins (APH and KPH content) 3-6 months after the correction of urodynamics made it possible to establish the following.
Thus, after treatment, the average level of APH in serum decreased: in 11 (73.33%) children of the main group; in 11 (73.33%) children of the control group.
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Serum KPH indicators decreased: in 19 (67.85%) children of the main group; in 19 (67.85%) children of the control group.
This indicates the positive dynamics of changes in the level of these markers and the gradual restoration of the functioning of the organs of the urinary system as a result of the treatment.
At the same time, 13 children (30.23% of patients) had an increase in the level of APH and KPH indicators
in the postoperative period. This was observed in 4 children (26.66% of cases) of the main group for APH and KPH, and 9 children (32.14% of cases) of the control group.
Generalizing characteristics of the number of positive results and cases in which the expected improvement was not achieved, according to the indicators of markers of oxidative stress and the state of the antioxidant system after surgical treatment of primary obstructive megaureter in children, is presented in Table 3.
Table 3
Changes in indicators of markers of oxidative stress and the state of the antioxidant system after surgical
treatment.
Metabolites of nitrogen oxide Products of protein peroxidation
NO NOS APH KPH
abs % abs % abs % abs %
Main group (n=15) Improvement 8 53,33 7 46,66 11 73,33 11 73,3
Unchanged 1 6,66 1 6,66 0 0
Deterioration 6 40 7 46,66 4 26,66 4 26,6
Control group (n=28) Improvement 17 60,71 15 53,57 19 67,85 19 67,85
Unchanged 2 7,14 2 7,14 0 0
Deterioration 9 32,14 11 39,28 9 32,14 9 32,14
Generally (n=43) Improvement 25 58,13 22 51,16 30 69,76 30 69,7
Unchanged 3 6,97 3 6,97 0 0
Deterioration 15 34,88 18 41,86 13 30,23 13 30,2
where n - number of children.
Discussion.
In the comparative analysis of markers of oxidative destruction of proteins (APH and CPH levels) and nitric oxide metabolites (NO and NOS indicators) before and 3-6 months after the restoration of urodynam-ics, the variability of the response of the functional state of the organs of the urinary system was determined. Thus, in response to the restoration of urodynamics, a decrease in the manifestations of oxidative stress was noted in some patients - in 58.13% (NO), 51.16% (NOS), 69.76% (APH) and 69.76% (KPH).
However, in a certain part of patients, despite the recovery of urodynamics, manifestations of damage to the organs of the urinary system remain - in 34.88% (NO) and 41.86% (NOS). Such data indicate that uro-dynamic disturbances were so significant that their operative correction did not lead to significant functional normalization.
Thus, a decrease in the levels of APH and KPH excretion after surgical treatment of primary obstructive megaureter are significant indicators of the effectiveness of restorative processesin the kidney parenchyma; the absence of positive changes in these parameters, on the contrary, indicates a low probability of recovery of the kidney parenchyma after the final correction of urodynamics.
Therefore, determination of APH and KPH content in blood serum are informative diagnostic and, to some extent, prognostic markers of reversibility of changes in the kidney parenchyma after surgical treatment of congenital megaureter in children.
Conclusions.
Evaluation of the effectiveness of treatment of primary obstructive megaureter in children should include
not only the characterization of the state of urodynamics of the urinary tract, but also the characterization of the functional state of the operated organs of the urinary system, which is determined on the basis of minimally invasive techniques that allow detecting pathological disorders with a high degree of probability [4]. It is the indicators of the functional state of the urinary system that should be taken into account as the main markers of a positive or negative result of a child's treatment [8]. In recent years, minimally invasive methods for assessing the functional state of the kidneys have been rapidly developing, which include determining the levels of these biochemical markers of oxidative stress and the state of the antioxidant system [6, 10].
In this plan, the study of the content of markers of oxidative stress and the state of the antioxidant system, namely, the concentration of nitric oxide, NO-synthase, aldehyde-phenylhydrazones and ketone-phenylhydra-zones in the blood serum of children after correction of urodynamics are informative markers of the functional state of the kidney in general and signs of nephrosclerosis, in particular [7, 11].
Despite the improvement of urodynamics, the lack of positive dynamics of indicators of markers of oxidative destruction of proteins (APH and KPH) in 30.23%, metabolites of nitric oxide NO in 34.88% and NOS in 41.86% indicates that the functional capacity of the kidneys in a certain number of patients is not improving.
These data indicate the need for early diagnosis of primary obstructive megaureter in children and the use of staged treatment depending on the degree of urody-namic decompensation [1, 14]. When determining the evaluation of the effectiveness of the treatment, it is the indicators of the functional organs of the urinary system that should be taken into account as the main markers
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of a positive or negative result of the child's treatment [3, 5, 13].
Prospects for further research.
Currently, there is growing interest in the use of biochemical methods for the purpose of early (preclinical) detection of obstructive uropathy and clear differentiation of organic and functional causes of urinary tract enlargement. The most promising in this direction is the use of accurate markers of renal function in the clinical prediction of the course of pyelonephritis, the state of the kidneys and urinary tract, the choice of management tactics and treatment of children with obstructive uropathy.
Conflict of Interest: None.
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