Antihypoxic effect of almid-containing metal-complex compounds in the experiment

Abstract

BACKGROUND: Nowadays, to increase resistance to hypoxia, various methods of hypoxic training, mental effects, as well as the use of pharmacological antihypoxants are practiced.
 AIM: to test new metal-complex compounds containing the antihypoxant Almid in experiments on mice under conditions of acute hypoxia to find protective properties.
 MATERIALS AND METHODS: At the first stage of the study, 4 new metal-complex compounds of magnesium, calcium, titanium and vanadium containing the antihypoxant Almide were screened in experiments on mice (n=550) in conditions of acute hypoxia with hypercapnia (AH+Hc). Antihypoxants Almid and Amtizole were used as comparison substances. The state of acute hypoxia was caused by placing animals in pharmacy glasses with a volume of 0.25 liters closed lapped stoppers. The substances were administered intraperitoneally in doses of 25, 50 and 100 mg/kg, previously dissolved in 0.3 ml of NaCl solution. The incubation period was 60 minutes. The antihypoxic effect was considered proven with an increase in lifespan by 20% or more. By "lifespan" was meant the time interval from the moment the mice were placed in a pharmacy glass to the development of the first agonal inhalation, after which the animals were quickly removed in order to preserve life. Rectal temperature was measured in animals before the introduction of substances, immediately before being placed in the conditions of AH+Hc and after removing. In 24 hours after the first stage of the experiment, mice of the control group and mice that proved their ability to resist AH+Hc were repeatedly exposed to AH+Hc after the use of substances.
 RESULTS: A distinct antihypoxic effect exceeding the effectiveness of the comparison substances was obtained only in one substance – πQ2460 with titanium as a metal-complexing agent and a ligand in the form of fumaric acid. After administration of πQ2460 a dose-dependent decrease in rectal temperature was observed in mice. The lifespan of animals increased with an increase in the dosage of the substance πQ2460 – by 43.9%, 103.1% and 152.8% in accordance with doses of 25, 50 and 100 mg/kg. The results of the second stage of the experiment confirmed the stable protective effect of πQ2460 but with an equalization of the effect for the studied doses which provided an increase in lifespan under conditions of AH+Hc to an average of 60-70 minutes (in the control – 40.5 minutes).
 CONCLUSION: Among the compounds containing the antihypoxant Almide in the complex molecule, the substance πQ2460 (metal – titanium, ligand – fumaric acid) was found to have a stable protective dose-dependent effect in the development of acute hypoxia with hypercapnia in mice exceeding that for Almide and the reference antihypoxant Amtizole. The antihypoxic effect of the substance πQ2460 persisted 24 hours after administration but leveled off for the studied doses – 25, 50, 100 mg/kg. Taking into account the data obtained during the comparison of indicators of resistance to acute hypoxia in the control group, a hypothesis was proposed about the possibility of forming a preconditioning effect in animals from the primary effects of acute hypoxia.