The aim of the research was to investigate the effect of antihypoxant Les-589 application, a thiazolidine derivative, under hypoxic hypoxia in animals with various resistances to hypoxia. The study was conducted on sexually mature male rats that were divided in accordance with the sensitivity to hypoxia as high – (HR) and low (LR) resistant ones. Within each group, the male rats were divided into several subgroups: the 1st – control; 2nd and 3rd subgroups have been injected intraperitoneally the substance Les-589 (100 mg/kg), dissolved in Tween.

Animals of the 3rd subgroup within 45 min after administration of the substance Les-589 were subjected to hypoxic hypoxia exposure (identical to the altitude of 6000 m above the sea level) for 1 h. The substance Les- 589 was selected among 17 newly synthesized thiazolidine derivatives, considering data of PASS – QSAR system analysis. In the blood and liver of animals were determined the contents of the lipid peroxidation (LPO) metabolite – thiobarbituric acid – active products (TBA-AP), and the enzymes’ activity of antioxidant protection (AOP): superoxide dismutase (SOD) and catalase, concentration of nitric oxide cycle metabolites – nitrite ions. Based on the received data, an integrative factor K = AOA/LPO has been calculated – the ratio of all AOP parameters to the intensity of lipid peroxidation processes.

It has been established that hypoxic exposure leads to the initiation of free radical peroxidation processes in blood and liver tissue of HR and LR animals. In this case, it is important to conduct a comprehensive evaluation of the studied parameters of free radical homeostasis by integrative calculation for total balance of opposing factors –LPO and AOP components (K=AOA/LPO). Accordingly, the coefficient (at a rate K=100%) under hypoxic exposure is manifested by a sharp decline in its value in the blood and liver tissue of animals of both groups. This directly depends on the initial level of resistance of animals to hypoxia and is evidence of desadaptation.

The conducted calculations prove a highly informative significance of K=AOA/LPO in the corresponding experimental groups using antihypoxant Les-589. It has been noted a significant increase of the coefficient in the blood and liver tissue of both experimental groups (for appropriate examined groups without correction). This is an evidence of the trend towards the restoration of free radical homeostasis and favourable type of adaptive response.

Living of animals under conditions of hypoxic hypoxia was accompanied by a probable increase in the concentration of nitrite ions comparing with its level in the blood of HR animals by 48%, in liver tissue – by 25%. The level of the metabolite in the blood of the LR animals increased in comparison with control by 31%, in the liver tissue – by 24%. Effect of preventive administration of potential antihypoxant was detected as a probable decrease in the concentration of nitrite ions in comparison with investigated groups, for which the examined medicine was not applied. A general conclusion can be made considering that changes in the nitrogen cycle are involved into processes leading toward homeostasis balance of free radical reactions within the studied conditions.

Thus, on the basis of the carried out analysis of parameter changes characteristics of free radical homeostasis in the blood and liver tissue of animals with different resistance to hypoxia it has been proved, that the most informative for assessing the type of adaptive response and efficacy of the investigated pharmaceutical is an integrative factor K=AOA/LPO. The involvement of the cycle of nitric oxide metabolites as paracrine regulators of oxidative metabolism under conditions of hypoxic hypoxia and its correction was determined.

Ключові слова: antihypoxants, lipid peroxidation – antioxidant activity (LPO / AOA), nitric oxide, free radical homeostasis

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