Oxidative stress and components of antioxidant defense in the mechanisms of formation of bronchial asthma in children

Abstract

Bronchial asthma (BA) is a chronic disease with a complex multicomponent mechanism of development and progression. A significant increase in its prevalence in the pediatric population necessitates the search for some new possibilities for prevention and treatment taking into account the peculiarities of the child’s organism, including adaptive mechanisms, not only on the organism but also on the cellular and molecular levels. An important role in the pathogenesis of the vast majority of diseases of the respiratory tract, including bronchial asthma (BA), is oxidative stress (OS), the main cause of which is the imbalance in the system of "oxidants-antioxidants", which is expressed by the excessive formation of active forms of oxygen (AFO) and weakening the effectiveness of antioxidant protection (AOP). By now it was proved that in the state of oxidative stress, under the influence of AFO, not only lipids, but also proteins of plasma membranes are subjects of peroxidation. It is believed that the negative effect of oxidation modified proteins in cells is connected with the fact that oxidized proteins are the source of free radicals that deplete the stores of cellular antioxidants. Products of free radical oxidation of proteins lead to oxidative DNA damage. In this case, peroxide oxidation of proteins (POP) is not only a trigger mechanism for pathological processes in stress, but also the earliest marker of oxidative stress. The dynamics of changes of the POP products is a reflection of the degree of oxidative cell damage and of the reserve and adaptive capacity of the body. It is believed that the level of indicators of oxidative modification of proteins (OMP) compared with the level of LPO is more informative marker of the presence of oxidative stress in the body. The aim: to study the state of the prooxidant system and the system of antioxidant protection in children with varying degrees of control of BA. Materials and methods: The study involved107 children aged from 10 to 18 years old, with asthma under exacerbation. According to the results of the Asthma Control Test (GINA, 2014) regarding the level of control of BA, children were divided as follows: 34 (31.8%) – with controlled (CBA), 47 (43.9%) – with partially controlled (PCBA) and 26 (24.3%) with uncontrolled bronchial asthma (UCBA). The control group consisted of 10 practically healthy children of the same age. It was established that children with low level of control have a prooxidant activation, which is manifested by a significant increase in the level of oxidation modified proteins. Results: The index of oxidative modification of proteins (OMP) -356, amounting to (0,293 ± 0,006) RVU (relative value unit) was significantly higher in children with uncontrolled bronchial asthma (UCBA) compared with the patients in other groups (p <0.05). The maximum value of OMP-370 was registered in a group of patients with UCBA. This figure was significantly higher than that of those with a higher level of disease control (p <0.05). Another trend was noted due to OMP-430 content indicators. Thus, a probable increase in its level was observed only in children with UCBA (pN<0.05). The content of OMP-530 in children with UCBA was practically the same with that of the control group, and in children with partially controlled (PCBA) and controlled bronchial asthma (CBA), there was a significant decrease in the rates compared to healthy ones (pN<0.05). Thus, the obtained results demonstrate the systemic activation of the POP process in children with BA, which may be the result of a long inflammatory process. The amplification of POP processes is accompanied by a weakening of AOP, manifested by a decrease in the activity of SOD, which catalyzes the dismutation of superoxide anion radicals and the antioxidant barrier of the first line of defense – catalase and indicates a significant reduction in the protection of the respiratory tract in BA from the accumulation of active forms of oxygen. Conclusions: In children with CBA there is a development of oxidative stress, which manifests itself in a significant increase and accumulation of the content of POP products against the backdrop of increased tension of the adaptive mechanisms of contact-protective system AOP. BA in children is characterized by heterogeneity of mechanisms of peroxidation and enzymatic maintenance of the prooxidant system, which is determined by the severity of the course of the disease and can be a pathogenetic basis for predicting the severity of BA in children. At the same time, we can observe weaken of the antioxidant protection in these patients, which is evident by a significant decrease in the activity of superoxide dismutase enzymes and, in particular, catalase.