Efficacy of ethylmethylhydroxypyridine succinate derivative in a model of intermittent hypoxia in comparison with the reference drug

Introduction. Intermittent hypoxia (IH) promotes oxygen free radical oxidation, which may precede many diseases. Decreased physical activity, ischaemic processes in organs and disturbances at the cellular level, may be a consequence of intermittent hypoxia. It is important to search for potential drugs to correct this process.

Aim. Comparative study of the efficacy of the active metabolite of ethylmethylhydroxypyridine succinate (EMHPS), ethylmethylsulfapyridine (EMSP), with a native molecule in a model of IG in mice.

Materials and methods. Test subjects were administered intraperitoneally for 14 days – EMSP was administered at a dose of 85 mg/kg, Mexidol® – at a dose of 100 mg/kg. Prolonged intermittent hypoxia was reproduced by placing animals in a membrane hypoxifier. The following conditions have been set for 14 days: 6 % – oxygen content in the hypoxic chamber, duration – 6 hours. The effect of the drug on dynamic load (grip strength test), respiratory parameters (plethysmograph parameters), behavioral and cognitive parameters (open field and elevated plus maze tests), heart rate and venous oxygen saturation were evaluated, and the potential mechanism of action was studied by real-time PCR.

Results and discussion. It was found that EMSP was effective in terms of plethysmography parameters, in particular, it helped the body adapt to chronic hypoxic effects, which resulted in significant differences in inhalation and exhalation parameters from the control group. The study of behavioral and cognitive states revealed the presence of anxiety, decreased exploratory activity and increased mobility of animals in all groups. These parameters were less pronounced for animals treated with EMSP and Mexidol® than in the control group. There was a tendency to increase the expression of a gene affecting the ubiquinol-cytochrome c-reductase complex, which is a part of mitochondrial respiration.

Conclusion. According to the results of the study, EMSP showed comparable protective properties with a native molecule EMHPS. There was also a tendency to increase the stimulation of UQCRC2 gene against the background of EMSP administration compared with EMHPS.

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