Exploring novel pharmacological approaches to acute hypoxic preconditioning

BACKGROUND: Metal compounds, particularly transition metal salt with various structural complexities, often demonstrate the pro-hypoxic effect. This effect can be used for acute exogenous hypoxic preconditioning. AIM: The work aimed to assess the potential of specific metal complexes as pharmacological agents for acute exogenous hypoxiс preconditioning in an experimental setting. MATERIALS AND METHODS: The experiments were conducted on 140 male CBF1 mice weighing 20–25 g. Acute exogenous hypoxia was simulated using two methods: by placing animals in an enclosed space to induce acute hypoxia and hypercapnia, and by simulating the high-altitude environment to induce acute hypobaric hypoxia. The mice’s tolerance to hypoxia and hypercapnia was evaluated by measuring life expectancy, whereas spare time was used to assess the tolerance to hypobaric hypoxia. The metal complexes πQ1983, πQ2116, and πQ2721—which have been shown to have antihypoxic effects—were administered to mice daily by single intraperitoneal injection at 10, 25, and 40 mg/kg for 7 days prior to the experiments. At 10:00 a.m. on day 8, the animals were exposed to modelled acute exogenous hypoxia to assess the preconditioning effect. The effect of the compounds on thermogenic processes was evaluated by measuring rectal temperature. RESULTS: Of the 3 compounds examined, only πQ2721 showed the preconditioning effect in the acute hypoxia and hypercapnia model. After 7 days of administration at 25 and 40 mg/kg, animal life expectancy increased by 56.5 % and 82.6 %, respectively. Each compound demonstrated a beneficial effect on the mice’s tolerance to acute hypoxia in the acute hypobaric hypoxia model. CONCLUSION: In two models of acute, exogenous hypoxia, all three metal complexes—πQ1983, πQ2116, and πQ2721—that were investigated in mouse experiments showed the preconditioning effect, which was most significant in acute hypobaric hypoxia conditions. In contrast to πQ1983 and πQ2116, πQ2721 exhibited the significant dose-dependent preconditioning effect in models of acute hypoxia and hypercapnia and acute hypobaric hypoxia that considerably enhances the animal tolerance to oxygen deficiency. The preconditioning effect of metal complexes is most effectively achieved in conjunction with the induction of hypothermia, which can serve as a valuable marker in the targeted search for novel pharmacological agents for preconditioning.