Study of metabolic disorders in rats under exposure to hypobaric hypoxia and development of ­correction approaches by simultaneous action on different elements of pathogenesis

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Abstract

Aim. To study the indicators of metabolic changes in the blood and brain structures of rats after exposure to hypobaric hypoxia and to determine possible pharmacological approaches to correction these changes.

Methods. Hypobaric hypoxia in rats was simulated for 30 minutes in a pressure chamber, simulating an ascent to 8500 m. 3 and 24 hours after hypoxia, the activity of alanine aminotransferase, aspartic aminotransferases, alkaline phosphatase, creatine phosphokinase, lactate dehydrogenase, the content of glucose, total protein, triglycerides, cholesterol, β-lipoproteins, iron and uric acid were determined in the blood serum. The level of malondialdehyde in the hippocampus and frontal cortex was examined. The studies of the effect of 2-chloroethoxy-aryl-dimethyl-aminophenylphosphorylacetohydrazide (CAPAH) (1 mg/kg) and Рiracetam (100 mg/kg) after intraperitoneal injection 40 minutes before hypoxia and 1 hour after removing the rats from the pressure chamber were carried out. Statistical analysis was carried out using the GraphPad Prism software version 8.0.1, and the Student's t-test was used to test statistical significance.

Results. After 3 hours of hypobaric hypoxia, rats showed hyperenzymemia and dyslipidemia, the activity of almost all studied enzymes in the blood serum of rats was increased, the content of triglycerides was decreased, and the concentration of cholesterol was increased, the content of malondialdehyde in the hippocampus and frontal cortex was increased. In 24 hours after hypoxia, an increased level of creatine phosphokinase in the blood serum and malondialdehyde in the brain structures were noted. The use of 2-chloroethoxy-aryl-dimethyl-aminophenylphosphorylacetohydrazide prevented the development of hyperenzymemia, dyslipidemia and corrected the increased level of creatine phosphokinase after 24 hours; in both modes of administration, it reduced the serum level of malondialdehyde. Piracetam showed little effect only when administered prophylactically, preventing an increase in serum alkaline phosphatase activity and cholesterol levels.

Сonclusion. The revealed efficacy of 2-chloroethoxy-aryl-dimethyl-aminophenylphosphorylacetohydrazide and its previously studied complex mechanism of action suggest that 2-chloroethoxy-aryl-dimethyl-aminophenylphosphorylacetohydrazide is a potential drug for the prevention of hypoxic disorders and acceleration of adaptation to high-altitude hypoxia.

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About the authors

I I Semina

Kazan State Medical University

Author for correspondence.
Email: seminai@mail.ru
Russian Federation, Kazan, Russia

A Z Baychurina

Kazan State Medical University

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

E V Shilovskaya

Kazan State Medical University

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

N E Tikhonova

Hospital for War Veterans

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

D O Nikitin

Kazan State Medical University

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

E V Begichev

Republican Clinical Hospital

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

A G Ovchinnikova

Kazan State Medical University

Email: seminai@mail.ru
Russian Federation, Kazan, Russia

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Supplementary files

Supplementary Files
Action
1. Рис. 1. Активность ферментов в сыворотке крови крыс через 3 ч после воздействия гипобарической гипоксии (ГГ) при введении 2-хлорэтокси-арил-диметил-аминофенилфосфорил-ацетогидразида (КАПАХ; 1 мг/кг внутрибрюшинно) и пирацетама (100 мг/кг внутрибрюшинно) за 40 мин до помещения крысы в барокамеру. По оси абсцисс — названия ферментов; по оси ординат — активность ферментов (%) по отношению к контрольным значениям, принятым за 100%. Количество крыс в каждой группе n=10. АЛТ — аланинаминотрансфераза; АСТ — аспартатаминотрансфераза; ЛДГ — лактатдегидрогеназа; ЩФ — щелочная фосфатаза; КФК — креатинфосфокиназа; *разница достоверна по отношению к контролю; **разница достоверна по отношению к ГГ.

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