Thiotriazoline Influence on the Nitric Oxide Indicators under the Conditions of Experimental Bronchial Asthma

The purpose of the research is to examine the activity of nitric oxide synthase (endothelial and inducible), arginase activity of peripheral blood lymphocytes of Guinea pigs with experimental asthma before and after thiotriazoline treatment. Materials and methods. All experiments on laboratory animals carried out with following the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes (Strasbourg, 1986), Council Directive 2010/63/EU, Ukrainian Law 3447-IV “Animals protection against cruelty”, the general ethics of animal experimentation adopted by the first national Congress on bioethics in Ukraine (2001). The researches were carried out on 180 Guinea-pigs. The weight of each one was 180-220g. They were divided into 6 groups for 30 animals in each. Among the first group (control) there were intact Guinea-pigs. Among the II group there were animals with an experimental BA (on 5th day of experiment). Among the III group there were Guinea-pigs on the 19th day of the experiment. The IV group consisted of animals with an experimental BA (on 26th day of the experiment), the V group included Guinea-pigs with an experimental BA (33rd day) and the VI – guinea-pigs with BA on 33 days after treatment with thiotriazoline which was given intramuscularly at a dose of 100 mg weight for 10 days. Two periods of experimental asthma were separated in order to make detailed analysis and interpretation of indicators of endogenous intoxication in different days of the experiment: early period and late one. The early period included a group of animals with BA on the 5th and 19th days of the experiment. Late period included Guinea pigs on 26th and 33rd day of asthma. The experimental asthma model reproduced in Guinea pigs by Babich method (1979). Animals were sensitized by a normal horse serum (0.1ml intraperitoneally). Next three days they were entered subcutaneously 0.1 ml of normal horse serum (NKS) with a setting in an autoclave BCG (1 mg BCG 1.0 ml NKS). The next 14 days animals were exposed to inhalation (using a spray) NKS to 1.0 ml of serum for each Guinea pig daily for 30 minutes in a sealed chamber. After this period every 7 days, Guinea pigs had such NKS inhalation. Then the animals were decapitated under the influence of ether anesthesia. In all groups of Guinea pigs there were determined NO synthase activity by specific cleavage NADPH (H +), arginase lymphocyte activity by the formation of urea. Numerical results were adapted with static method using Student's criteria. Research results. As a result of current study there were changes found in the activity of arginase-NO-synthase system of blood lymphocytes, which improve arginase activity of lymphocytes and increased activity of inducible NO-synthase and, at the same time, compensatory inhibition activity of endothelial isoforms of NOS in blood, thus these indexes were most expressed on the late stages of her forming (33rd day). The use of thiotriazoline in curative aims stipulated the decline of arginase lymphocyte activity on 32,5% (r≤0,05), considerable increase of content of еNOS in blood on 51,1% (r≤0,05) and decline of іNOS on 32,1% (r ≤0,05) at experimental asthma as compared to the group of animals that did not yield to influence of this medication. Conclusions. Thus, according to obtained data, thiotriazoline usage showed correcting influence on the changed indexes of metabolism of nitric oxide in peripheral blood of guinea-pigs at the terms of experimental bronchial asthma development.