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Section 7. Medical science
Akramova Khursanoy Abdumalikovna, Tashkent Pediatric Medical Institute, Ambulatory Medicine Department, assistant E-mail: [email protected] Akhmedova Diloram Ilkhamovna, Republican specialized scientific-practical medical center of pediatrics, Director, DM, Professor Khaibullina Zarina Ruslanovna, Tashkent Pediatric Medical Institute, Department of biological, bioorganic and inorganic chemistry, Professor, DM
Diagnostic significance of oxidative stress markers in underweight new-born babies on the initial days of life in the prognosis of adaptation disorders (experimental study)
Abstract: Study of the level of oxidative stress and activity of anti oxidative stress in underweight young rats during initial days of life provided identification of intensification of generation of oxygen active forms in brain, blood and microsomal-cytosol fraction of liver, expressed in various degrees, and also anemia present at the birth and progressing during the initial days of life. These factors are important for adaptation reaction of an organism. Keywords: oxidative stress, retardation of fetal development, adaptation, new-born.
Retardation of fetal development is one of universal reac- day after birth, the most important period on which early and tions of a fetus as a response to unfavorable impact within in- late prognosis depend [5]. In relation to that it is interesting
to study potential prognostically significant parameters, such as hemogram and intensity of oxidative stress during initial 24 hour after birth.
Objective: to study the dynamics of oxidative stress during initial day of life and contribution of certain organs and tissues to systemic OS.
Materials and methods. Modeling of the retardation of fetal development was performed in chronic experiment. The object of the research was white pedigreeless rats: pregnant females underwent chronic hypobaric hypoxia with 41.1 kPa (308 mm. of mercury column), at 2 weeks of gestation term 10 folds (n=14), rate of compression and decompression was 0.5 kPa/min. Exposition in the conditions of rare air and oxygen deficiency was 1 hour. The chosen model meets the requirements of the experiment, as in the result of high altitude hypo-baric hypoxy there is occurrence of disorder of placental blood supply in females and development offetal-placental insufficiency (FPI) — one of the important factors of retardation of fetal development. New-born rats were studied after birth (n=65).
Samples of peripheral blood, homogenates of brain and microsomal-cytosol fraction of liver were studied in various hours of the first day of life: at the birth, 1,3,6,12, and 24 hours.
In biomedia we determined the level of active forms of oxygen (AFO) generation according to the amount of malonic dialdehyde (MDA) by means of I. D. Stalnoy et al., activity of super oxide dismutase (SOD) was determined according to the rate of auto oxidation of adrenalin with the help method of Mirsa P. H., Fridovich I., activity of catalase (CAT) — according to Bach-Zubkova's method, and the parameters of hemogram with the help of automatic hematological analyzer MINDRAY BC-3000.
tra uterine development, conditioned by maternal risk factors, pathology of placenta or pathology of fetus itself [7]. The part of stillborn preterm babies with retardation of fetal development was 62.8%, and the part of dead in perinatal period was 41.9%, perinatal and neonatal morbidity was 2-8 folds higher, than among the children, born with body mass corresponding to the term of gestation [4], and that dictates the necessity of study the peculiarities of underweight children's adaptation.
According to the results of 14-years follow-up we determined four clinical characteristics possessing prognostic value in the estimation of survival ability of a new-born in 23-24 weeks of gestation with low weight (LW) as follows: systolic arterial pressure, respiratory index, hemoglobin and deficit of bases controlled during the initial 6 hours of life [6]. Early cardiac-pulmonary adaptation and original level of hemoglobin at birth were leading factors, which defined survival ability in preterm babies with low weight. Exactly the level of hemoglobin at birth is associated with early outcome in newborn babies up to 32 weeks of gestation [3].
Oxidative stress (OS) is one of leading damaging factors in the pathogenesis of retardation of fetal development [2]. It was found out that, the level of 8-oxy-2-deoxyguano-sine in urine (the product of oxidative degradation of DNA, OS marker) of children with low weight was increased proportionally to the body weight deficit, but only during initial days of life. At the 30th day that value correlates with the dose of received oxygenation, i. e. it is higher in the new-born babies, who received oxygen compared with those who didn't [1]. These interesting results show that, prognostic value for the definition of the risk of adaptation disorder in new-born babies with LW is valid for the values defined during initial
Diagnostic significance of oxidative stress markers in underweight new-born babies on the initial days.
Results. We revealed that, female rats which underwent unfavorable impact (hypoxia) born young rats with retardation of height-weight parameters compared with the animals of the control group. So the deficit of the weight at birth was 18.1± 3.4%.
Young rats of the control group had alterations of MDA level, activity of SOD and CAT during initial hours of life with unauthentic character, indicating stationary generation of AFO in initial 24 hours of life.
Young rats of experiment group born with low weight by the female rats, which underwent chronic hypoxia and modeling of FPI, in the first hour after birth had notable higher amount of MDA in comparison with the control values in all examined organs: in homogenate of brain the increase in relation to the control was 1.4 folds, in microsomal-cytosol fraction of liver (MS) to 1.8 fold, and in blood to 2.1 folds. That indicates development of oxidative stress in the fetal organism during the period of fetal development and its contribution to systemic OS of brain tissues and liver.
In 1 hour after birth there is notable growth of MDA level: in brain to 56%, in blood to 51%, in MS to 91% in relation to previous term. In 3 hours after birth growth of MDA in liver continues (to 58%) and in blood (to 152%), and in brain tissues we noted some decrease of MDA concentration in relation to the previous term. In 6 hours growth of MDA was noted only in MS of liver (to 10%), and in brain tissues there was stabilization of that value on a stationary high level, in blood the level of MDA decreased 1.75 fold in comparison with the previous term. Further, in 12 and 24 hours concentration of MDA in Ms of liver gradually continued it growth, in brain it again increased 2.2 folds above the control values, and in blood it decreased a little bit, but still was 4.3-3.2 times higher than normal.
Revealed dynamics of MDA level in various biological media indicates that, intensity of OS is different in brain, MS and blood within initial 24 hours of life in low weight young rats of the experimental group. The earliest intensification of AFO generation was noted in brain tissues in the first hour of life (increase 2.2 folds in comparison with the control), and in liver the intensity of OS reaches its maximum to 12-24 hours (increase 6.7 folds in relation to the control). In brain tissues after reaching its peak OS stayed stationary high (alterations of MDA level at 3,6, and 12 hours after birth were statistically unauthentic to each other), and intensified to 24th hour of life. In MS of liver there was progressive intensification of OS. These data indicate earlier exhaustion of endogenic anti oxidant
power of brain tissues with washing out of lipo peroxidation toxic metabolites to blood. At the same time in liver there is stronger activation of AFO generation, compared with brain tissues: increase of MDA 6.8 folds in MS versus 2.2 fold increase in brain in "peak" terms. It is possibly conditioned by redistribution of anti oxidant power from anti oxidant deposit — liver to brain, the organ, which is more important for life and more vulnerable to AFO impact as a result of activation of detoxificative function of liver MS. Maybe that conditions stationary high amount of MDA in brain tissues and rise of its concentration in MS of liver during initial 12 hours of life. In 24 hours after birth there is exhaustion of both proper and reserve anti oxidative power of brain tissues, which serves to be precondition of OS progressing.
The obtained results testify early activation of OS in the brain of low weight rats, reflection of which in blood appear only in 3 hours, and it should be taken into account that, intensification of AFO generation in MS of liver is not accompanied by the rise of MDA in blood. Increase of MDA in blood in 3 hours of life indicates development of Os in brain tissues, while decrease of MDA in blood in 24 hours doesn't indicate liquidation of Os in brain. As it is possible to judge about OS intensity in new-born baby according to MDA level in blood, it is reasonable to detect it within initial 3 hours of life, as well as the activity of anti oxidant system (AOS) enzymes.
Conclusions.
1. Unfavorable impact during pregnancy period leads to the birth of descendants with low weight, anemia and high level of AFO generation in brain, MS of liver and blood at the moment of birth.
2. Oxidative stress in brain tissues of the generation of low weight rats born by female rats, which underwent modeling of FPI, intensified during the first hour of life and preserves at the stationary high level during 24 hours, and it can be precondition for the disorder of adaptation and development.
3. The peak of oxidative stress intensity occurs in brain within the first hour of life, in blood in 3 hours, in microsomal-cytosol fraction of liver in 12-24 hours of life, and it was linked with the redistribution of anti oxidant stress power and wash out of toxic metabolites to blood.
5. The level of malonic dialdehyde in blood, activity of super oxide dismutase and blood catalase, measured in 3-24 hours of life, change not proportionally to the intensity of oxidative stress in brain and microsomal-cytosol fraction of liver, reflecting the total level of anti oxidant stress in blood in greater degree.
References:
1. Khaibullina Z. R. Development of antiradical protection of brain in post-natal period as the basis for the design of new approach to the therapy of cerebral ischemia in new-borns//Infection, immunity and pharmacology. - 2012. - № 1. - P. 125-131.
2. Sherbachenko I. M. Erythrocytes Modified by oxidation as an experimental model for the evaluation of anti oxidants activity: Abstract of dissertation. ...Cand. Boil. Sc. Moscow, 2008. - 23 p.
3. Al-Abdi S. Y., Al-Aamri M. A. A Systematic Review and Meta-analysis of the Timing of Early Intraventricular Hemorrhage in Preterm Neonates: Clinical and Research Implications.//} Clin Neonatol. 2014 Apr; 3 (2): 76-88.
