Vol 16, No 2 (2025)

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.

Type 2 diabetes mellitus is characterized by its high prevalence among the elderly and senile populations. It is estimated that approximately one in five individuals aged 65 or more live with diagnosed or undiagnosed type 2 diabetes mellitus. These estimates support the reasonable hypothesis that the disease is associated with advanced age. Of particular relevance is the observation that type 2 diabetes mellitus in geriatric practice often co-occurs with neurological and psychiatric disorders.

A comprehensive analysis of the scientific studies published over the past 5 years by Russian and international authors offers a detailed description and discussion of the potential risks associated with hypoglycemic pharmacotherapy for type 2 diabetes mellitus in elderly and senile patients with neurological and psychiatric disorders. This study provides an overview of the pharmacodynamic characteristics of the main classes of hypoglycemic agents, thereby facilitating an assessment of their safety in geriatric populations. The following discussion addresses the requirements and principles of hypoglycemic pharmacotherapy in elderly patients, with the aim of reducing the risks of adverse reactions. Metformin has been identified as the hypoglycemic agent with the lowest risk of adverse reactions for elderly and senile patients with impaired central nervous system function who are treated for type 2 diabetes mellitus. Novel groups of antidiabetic medications, such as incretin mimetics and gliflozines, have emerged as promising candidates for treatment. Sulfonylureas, glitazones, and glinides are not recommended for elderly individuals.

Dexmedetomidine demonstrates cardioprotective effects for various non-cardiac surgical procedures, including those on the aorta, vessels, and hip joint. A significant aspect of the mechanism of dexmedetomidine as an α₂-adrenoceptor agonist involves its sympatholytic effect. The observed effects of dexmedetomidine are associated with its ability to stabilize hemodynamics and reduce the incidence of intraoperative myocardial ischemia. Experimental and clinical evidence has demonstrated that sympatholytic drugs, such as ganglion blockers in doses that block sympathetic ganglia, sympatholytics, and epidural anesthetics, have a cardioprotective effect by preventing the sympathetic dysregulation of trophic processes in the myocardium. Dystrophic changes in the myocardium, induced by the experimental irritation of the reflexogenic area of the aortic arch in rats and rabbits, were prevented by the prior administration of ganglion blockers and sympatholytics. The similar effects were observed in clinical trials with cardiac surgical patients who received epidural anesthetics, which also have a sympatholytic effect. The cardioprotective effect of dexmedetomidine is associated with the prevention of intraoperative neurogenic (reflex) myocardial dystrophy. This effect is achieved by inhibiting the irritation of the reflexogenic areas during periods of sympathoadrenal overactivation, thereby preventing the myocardial depletion of the neurotransmitter noradrenaline and the onset of neurogenic (reflex) dystrophic changes.

The meaningfulness of the research findings is largely determined by the depth of statistical processing and the quality of their presentation. However, the paucity of high-quality statistical analysis and data presentation poses a significant challenge for maintaining the consistency of published research results. Incorrect processing of primary data can result in distorted conclusions and significantly complicate the generalization of data on a specific research topic. The authors discuss the most frequent and incorrect techniques used in working with initial data and planning an experiment, including issues related to the calculation of sample size, the incorrect use of statistical tests, the identification of numerical statistical parameters and descriptive statistics, and the use of goodness-of-fit and data presentation tests. They also provide recommendations on the appropriateness or inappropriateness of specific methods. Graphic visualization requires that certain principles be followed. For normal distributions, the sample mean is the most practical measure for position. It is a generally accepted practice to show the standard deviation on the graphs as a measure of variability. Confidence intervals are also presented to offer a visual reference. Standard errors may also be represented, however, they are not indicative of data variability, but rather, they are an estimation of the difference between the sample mean and the mean population value. Medians are used to describe non-normal distributions because they are insensitive to outliers. In those specific cases, interquartile ranges (Q1-Q3) can be used as a measure of variability. In the context of large data sets, bar graphs, histograms, box-and-whiskers, and individual values may be considered to enhance the comprehension of visual presentations. The authors strongly advise against the use of tables for displaying large amounts of data, citing the challenges associated with reading such presentations.

Professor Petr D. Shabanov, Doctor of Sciences in Medicine (born June 30, 1955), is a prominent figure in both Russian and international pharmacology and physiology. As a famous scientist and expert in neuropharmacology of synaptotropic, peptide, and metabolic pharmaceuticals, he has extensively investigated the mechanisms underlying memory, behavior, emotional states, and various forms of addiction. Dr. Shabanov has achieved international recognition for his contributions, as evidenced by his extensive publication portfolio, which includes over 1500 scientific articles, 60 monographs, 60 textbooks, and more than 50 granted patents. He is a founder and permanent editor-in-chief of Reviews of Clinical Pharmacology and Drug Therapy (since 2003) and Psychopharmacology and Biological Narcology (since 2000). He is an active member of the editorial boards of more than 10 scientific journals. Dr. Shabanov has successfully supervised 36 habilitational and 65 PhD theses, and 22 of his graduates have become professors and heads of profile departments and research laboratories. His scientific career began in 1978 at the Scientific Research Institute of Experimental Medicine of the USSR Academy of Medical Sciences in Leningrad, where he worked under the supervision of academician Sergey V. Anichkov, a famous Soviet pharmacologist and member of the USSR Academy of Medical Sciences. In 1982, Petr D. Shabanov successfully defended his Ph.D. thesis in medical sciences, and subsequently earned his doctoral degree in 1992. From 2000 to 2022, he occupied the role of Head of the Department of Pharmacology at the S.M. Kirov Military Medical Academy in St. Petersburg. In 2011, he was elected as Head of the S.V. Anichkov Department of Neuropharmacology at the Institute of Experimental Medicine in St. Petersburg. Dr. Shabanov’s primary research areas focus on physiological and pharmacological aspects of memory, emotions, reinforcement, psychoneuroendocrinology, and problems of drug and non-drug addiction. He has developed 9 approved medications, including antihypoxants, neuroprotectors, nootropics, and anti-alcohol drugs. He contributed to the development of 23 biologically active food additives with ascorbic and succinic acids, which are currently manufactured in Russia.