The dissertation for the scientific degree of Candidate of Medical Sciences in specialty 03.01.01 "Radiobiology". – State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine", Kyiv, 2018.
The dissertation devotes of important scientific task in decision of important scientific task in radiation medicine, radiobiology and paediatrics, namely, improvement of children’s health using nitric oxide (NO) donators for correction of endothelial dysfunction on the basis of new scientific data about disorder of NO-metabolism, decrease of NO synthase activity of endothelium, risk of development of endothelial dysfunction in children living under protracted radiation exposure Cesium-137 (137Cs) and having polymorphism in intron 4 of the eNOS gene.
138 children living in the radioactively contaminated territories (RCT) and having the 137Cs whole-body counting results from 111 till 7067Bq, 49 children with the same nosology (group of ‘nosological’ control) and 27 health children aged 10 till 17 years were included in this study.
Children habitants of RCT had lower serum nitrite levels than children in group of nosological control: 6,65 ± 0,30 vs 8,63 ± 0,49 umol/l, respectively (р < 0,05). The renewal period of thermographic index of blood circulation after occlusion was bigger in children living in RCT than in ones at the group of ‘nosological’ control: 3,07 ± 0,20 vs 2,16 ± 0,23 minutes, accordingly (р < 0,01). These data were associated with the 137Cs whole-body counting result.
Inhibiting NO synthase activity of endothelium increased the risk of endothelial dysfunction development (RR = 2,351; 95,0 % CI: 1,356–4,077, р < 0,001). Moderate connection (φ = 0,306) between risk action and development of endothelial dysfunction was revealed.
Significant increase of final product of lipid peroxidation (LP) in children, who lived in the RCT, wasn’t established. At the same time, increased activity of catalase, indicating the compensatory stress of antioxidant system functioning, preservation of antioxidant protection reserves and the ability to neutralize TBK – active products of LP.
The frequency of bronchial hyperresponsiveness in RCD children was associated with endothelial dysfunction markers: a decrease in the level of nitrite (R = -0,392), an increase in the duration of the restoration of the circulation thermographic index to the baseline after occlusion (R = 0,274).
In children – residents of RCT with a genotype 4a/4b compared with children of the genotype 4b/4b, there is a marked decrease in the content of nitrite in serum, respectively (5,53 ± 0,26) umol/l and (6,99 ± 0,38) umol/l, p < 0,01 and an increase in the thermographic index of the duration of the restoration of blood circulation to the baseline after the occlusion, respectively (3,67 ± 0,25) minutes and (3,00 ± 0,21) minutes, p < 0,05.
These data of сarriers of the gene the minor allele a were associated with the 137Cs whole-body counting result.
Children with genotype 4a/4b had increased risk factor for endothelial dysfunction (RR = 1,600; CI: 1,168 – 2,192; p < 0,01), decrease in the elasticity, while the presence of the minor allele a of the 4th intron of the eNOS gene and the values of the in the integral index of airway patency – the FEV1/DFEV1 (r = -0,259; p < 0,05) and the FEV1/FVC (r = -0,2627; p < 0,05) had the inverse correlation.
The application of L-Arginine and Citrulline Malate decreased clinical symptoms, increased blood L-Arginine level, improved lung ventilation, indices of NO metabolism and indices blood circulartion after occlusion test, dicreased the 137Cs whole-body counting results (28% and 32%). Side effects were absent.
Key words: children, 137Cs, nitric oxide, 4a/4b polymorphism of eNOS gene, endothelial dysfunction, correction.
