Antioxidant effects of 2-ethylthiobenzimidazole and a complex of succinic acid salts in rats pre-trained to hypoxia with acute oxygen starvation

Abstract

BACKGROUND: The body’s response to hypoxia is largely determined by individual sensitivity to it. It has been shown that subjects with high resistance to hypoxia (humans and animals) are less susceptible to the damaging effects of hypoxia on the brain, myocardium, liver, and kidneys.

AIM: The experimental study of the antioxidant effects (indicators of lipid peroxidation and the activity of antioxidant systems in the brain) of 2-ethylthiobenzimidazole and a complex of succinic acid salts (amosuccinate) and their combination to increase individual brain resistance to hypoxia during interval hypoxic hypobaric training in rats.

MATERIALS AND METHODS: Acute hypoxic hypobaric hypoxia was induced in a flow pressure chamber. Rats were divided according to their resistance to acute hypoxia, raising them in a pressure chamber to a height of 11,000 m at a speed of 50 m/s and exposing them at altitude until agonal breathing occurred. Rats that were exposed to hypoxia for 5–10 minutes were considered low-resistant, and those exposed to hypoxia for more than 10 minutes were considered highly resistant. The interval hypoxic training regimen was 3 days. A one-day training cycle consisted of raising rats 6 times at a speed of 15 m/s to an altitude of 5000 m and exposing them to the height for 30 min. The interval between lifts is 20 minutes. The work used the synthetic adaptogen 2-ethylthiobenzimidazole hydrobromide (metaprot) 25 mg/kg and a complex of succinic acid salts (amosuccinate) 50 mg/kg, which were administered intraperitoneally for 3 days immediately after the end of a one-day training cycle. The control group consisted of trained and untrained rats that received saline. In the brain, the content of lipid peroxidation products (diene conjugates, malonic dialdehyde) was determined and the state of antioxidant systems was assessed (the content of reduced glutathione, the activity of catalase and superoxide dismutase).

RESULTS: Acute hypoxia caused excessive lipid peroxidation and decreased activity of antioxidant systems. Metaprot and amosuccinate in combination with hypoxic training prevented lipid peroxidation in the brain of rats. The content of diene conjugates in the brain of rats decreased by 12–26%, malonic dialdehyde by 13–58%. The drugs increased the content of reduced glutathione by 42–76%, catalase by 1.5 times, and superoxide dismutase by 1.5–2.2 times. The effect of the combined use of metaprot with amosuccinate was greater than that of the drugs alone.

CONCLUSIONS: The combination of high-altitude training with the use of synthetic alaptogens (metaprote and amosuccinate) increases the adaptive capabilities of the brain, which is confirmed by both an increase in survival time at altitude and a decrease in excessive lipid peroxidation and restoration of antioxidant systems.

Keywords

ethylthiobenzimidazole / amosuccinate / succinic acid salts / high-altitude hypoxia / adaptation / lipid peroxidation / antioxidant systems / brain / rats

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Funding

Министерство науки и высшего образования Российской Федерации (госзадание)Ministry of Science and Higher Education of the Russian Federation (state assignment)(FGWG-2024-0015)

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