Udc 615.23:612.015.11:546.172.6 Syrup Amkesol Reduces the Level of Primary and Secondary Products of Lipid Peroxidation and Toxic Metabolites of Nitric Oxide in Blood Serum of Immature Rats with Bronchiolitis

Introduction Broncho-pulmonary diseases are the most common childhood disorder [1] . In fact, 25-31% of children's respiratory infections lead to clinical manifestations of obstructive bronchitis, and in 30-50% of cases are having prolonged, undulate or recurrent course [2, 3]. Furthermore, recurrent obstructive bronchitis in children is considered to be a manifestation of bronchial asthma [4]. The alteration in the lipid peroxidation antioxidant protection (POL-AO) system and rising of nitric oxide are known to be essential in the development of bronchopulmonary pathology [5]. Basically, the major pathogenetic factor of bronchopulmonary pathology is chronic or acute inflammation, which clinically is manifested by swelling, hypersecretion, constriction of bronchi and hypoxia [6]. Obviously, inflammatory process induces “respiratory burst", that characterized by imbalance between lipid peroxidation and AO protection and accompanied by rising of NO [7]. In fact, it's allows to interpret the concentration of nitrates and N-nitro compounds in blood serum as a marker of acute nonspecific inflammatory process [8]. Thereby, reduction of primary and secondary products of lipid peroxidation and NO toxic metabolites and restoration of AO enzymes activity in inflammatory respiratory diseases have clinical significance and can be used as additional criteria to determine effectiveness of the therapy [9]. Besides, pathophisiologycal reactions of upper respiratory tract caused by infectious inflammatory process are age-depended due to anatomical and physiological characteristics of child's body. Therefore taking them into account is essential for the treatment of children with respiratory diseases [10]. For instance, one of the physiological responses of the first three years of life children is a sustain hyperproduction of highlyviscous mucus in combination with edema of bronchial mucosa, that subsequently violates second mucociliary transport, causes bronchial obstruction and promotes infectious inflammation [11]. Additionally, immune system of 2-6-years-old children is characterized by excessive proliferative activity of lymphocytes and higher levels of cell-mediated cytotoxicity compared with adults. Such phenomenon usually causes high sensitivity to infections and less specific response of the immune system. Moreover, for infants and children, the immune response to infectious antigens is predominantly Th2-response while in adults it is usually Th1-response [12]. Nowadays, comprehensive treatment of respiratory disease must include anti-inflammatory drugs along with conventional antimicrobial and symptomatic therapy. Apparently, the advantages of rational composition of combined medicines in the treatment of broncho-pulmonary diseases are they synergistic action on the pathogenesis, decreasing of the risk of side effects, and in finally avoidance of unintended interactions of individual drugs. As such this results in prevention of polypharmacy that is particularly important for functional immaturity of children’s organs and systems [13]. The problem of developing children's dosage forms, among which the oral solutions and syrups are most preferred, gains particular attention [14]. One of the recent combined preparation that recommended for the treatment of broncho-pulmonary diseases in Ukrainian pharmaceutical market is tablets Amkesol that manufactured by CPP "Chervona zirka", PJSC, Kharkiv, Ukraine [15]. According to the current needs of the Ukrainian pharmaceutical market to have an effective and safe pediatric medicine, it is important to develop and explore a child dosage form for Amkesol. The aim of this study was to determine the pharmacological effect of syrup Amkesol (S-AKS) (Ambroxol, ketotifen, licorice root extract) as a children analogue of tablets Amkesol evaluating the blood serum levels of primary and secondary products of lipid peroxidation, activity of AO enzymes and final rates of NO metabolites in immature rats of different ages with experimental model of bronchoalveolitis.