Vol 20, No 1 (2022)

The literature review is devoted to the generalization of publications on the toxicity of carbon nanostructures, which have recently been increasingly used in biological and pharmacological research, in medicinal chemistry with the prospect of being used in medicine. Analysis of the literature data shows that, despite a huge amount of work, there are no unambiguous conclusions about the toxicological characteristics of various types of carbon nanomaterials. The use of carbon nanostructures in medicine can be questioned due to the potentially adverse health effects of their use. To clarify the harmlessness, it is necessary to develop more effective tests on animals, taking into account the characteristics of each type of nanomaterial.

Feeding behavior includes both the satisfaction of metabolic nutrient requirements and the hedonic aspects of pleasure. The orexigenic hormone ghrelin increases motivation to food intake. In addition, by modulating the reward system, ghrelin enhances the rewarding properties of non-food stimuli. The dopaminergic mesolimbic system plays a key role in the mechanisms of reward. Ghrelin regulates the activity of this system by acting on several levels of brain organization. The hierarchy of ghrelin-sensitive neural networks, as well as afferent connections and reciprocal interactions between its components, mediating the effect of ghrelin on the process of motivation in metabolic and hedonic type of feeding are considered.

BACKGROUND: It is important to know the ability of a substance to penetrate the cell membrane to assess the bioavailability of drugs. The distribution of matter between the organic phase and water can be used as a model of the distribution between the membrane and extracellular fluid, and can be expressed by a partion coefficient, called logP.

AIM: The aim of this work was to determine the logP of 1H-imidazole-4,5-dicarboxylic acid (IDC) derivatives in various media and compare the values with theoretical ones.

RESULTS: As a result of the work, the distribution coefficients of the IDC derivatives were determined from the optical density data for a fixed wavelength of 250 nm (without a buffer). The distribution coefficients of the IDC derivatives over the maxima of the UV spectra (in the buffer) were determined. A comparison of theoretical and experimental values of the distribution coefficients of some IDC derivatives is carried out.

CONCLUSION: Thus, it has been shown that for a more accurate assessment of the bioavailability of drugs, it is not enough to rely only on the calculated logP index, it is necessary to conduct an experimental test, or introduce some correction factors to recalculate the theoretical logP index, in each specific class of compounds.

BACKGROUND: The state of hypoxia in natural conditions occurs in certain cases and is considered as a negative process in the overwhelming majority of cases. However, exogenous hypoxia is used as a factor of adaptation / preconditioning and training to the forthcoming hypoxic stress under some conditions, as well as increasing physical endurance and working capacity in normoxic conditions among specialists of various profiles. The mechanisms of adaptation to exogenous hypoxia have been studied in detail. Earlier in our studies, the value of artificial exogenous normobaric hypoxic hypoxia, which does not have a negative effect on the human body, was determined.

AIM: The aim of this work was to determine hypoxia inducible factor 1α (HIF-1α) as a possible marker of adaptation to normobaric hypoxic hypoxia.

MATERIALS AND METHODS: For 100 days, 6 test volunteers were continuously in a sealed residential test room based on the test bench of ASM JSC (St. Petersburg) in a state of normobaric hypoxic hypoxia (oxygen content 12–20%).

RESULTS: No clinically significant erythrocyte response to long-term exposure to normobaric hypoxic respiratory mixture was expectedly detected, although statistically significant fluctuations in the level of hemoglobin and the absolute number of erythrocytes were determined. When analyzing the HIF-1α concentration, qualitative data were obtained, characterizing a significant response (p < 0.05) in the change in HIF-1α concentration during the observation period. Additionally, a Kendall consistency factor of 0.68 was calculated, suggesting a significant difference in HIF-1α concentration dynamics.

CONCLUSIONS: The chosen mode of hypoxia can be used as a method of exogenous preconditioning.

BACKGROUND: A number of recent studies have revealed the role of orexins in regulating emotional behavior and emotional memory. The rationale for this role of orexin regulation is the close bi-directional interaction of orexin neurons with emotional structures of the brain, such as the bed nucleus of the stria terminalis, locus ceruleus, central and dorsomedial amygdala, hippocampus, medial prefrontal cortex. There is experimental and clinical evidence that an endogenous or induced deficiency of orexin effects accelerates the elimination of traumatic memory.

AIM: To study the effect of the OX1R Orexin Receptor Antagonist SB408124 and orexin on the emotional and exploratory behavior of animals after predator-induced stress.

MATERIALS AND METHODS: The experiments were made with 36 male Wistar rats, divided into 4 groups of 8 animals. Animals of 3 groups were exposed to single simulation of post-traumatic stress disorder by exposition with the indian python and subsequent death of one rat as a result of predator activity. The rats of 2 experimental groups received SB408124 OX1R antagonist in a dose of 20 µl of 0.1% solution and Orexin A in the same dose intranasally. The other animals received physiological solution in a dose of 20 µl intranasally. Behavior tests was made 7 days after the modeling of psychotrauma. A panel of behavioral tests was used: an elevated X-maze, an “open field” test, and an “resident–intruder” test. The obtained data were statistically processed using the Student t-test and ANOVA dispersion analysis. The differences were considered statistically significant at p < 0.01.

RESULTS: Orexin antagonist SB408124 showed anxiolytic effects. SB408124 showed anxiolytic properties in stressed rats. It restored the time spent in the light arm of the elevated X-maze to the intact level. In the open field test SB408124 increased (p < 0.01) the orientation behavior and reduced the frequency of freezing in stressed animals. Orexin A suppressed (p < 0,01) locomotor activity of animals in the open field. In the “resident–intruder” test in stressed animals SB408124 restored suppressed communication activity (p < 0,01). Orexin A reduced communicative behavior and increased aggression of animals.

CONCLUSIONS: The work shows a moderate anxiolytic action of SB408124 in the post-traumatic stress model in rats.

AIM: The aim was to assess the efficacy of treatment of asthenic syndrome in patients with combined injuries by means of succinate containing metabolic drugs (Mexidol, Cytoflavine, Metaprot plus) in comparison with non-succinate containing drugs of analogic structure or composition (Emoxipine, Riboxine, Metaprot) to clear up the significance of succinate as a functional structural element of the molecule.

MATERIALS AND METHODS: In 134 surgical patients and sufferers with combined injuries, an asthenic syndrome (high anxiety, depression, high psychic and physical tiredness, weakness, absent-mindedness, attention disorders, reduced physical and psychical ability, need in durative rest, high psychic exhaustion, social disadaptation) was revealed by clinical, psychological and instrumental methods.

RESULTS: Metabolic drugs containing succinate (Mexidol, Cytoflavine, Metaprot plus) in more degree than non-containing succinate in their structure (Emoxipine, Riboxine, Metaprot) were clinically effective in abolition or reduction of the asthenic syndrome in such patients. Antiasthenic action was represented by proper antiasthenic, antidepressant, anxiolytic, nootropic (cognitive) and positive general somatic effects of the drugs.

CONCLUSION: The data confirm that succinate in the structure (composition) of the metabolic drugs significantly enhances protective action against asthenic syndrome in surgical patients with combined injuries.

The work is devoted to the analysis of scientific research on the prevention of infectious diseases by adaptogens, proposed by a prominent domestic toxicologist and pharmacologist Professor Nikolai Vasilyevich Lazarev and the school of scientists he created. The role of adaptogens (dibazol, Eleutherococcus, Rhodiola rosea, Scutellaria Baicalensis) in creating a state of non-specifically increased body resistance (NSIBR according to N.V. Lazarev) for the prevention of viral diseases, including coronavirus infection, was evaluated. Analysis of the pharmacological properties of the synthetic adaptogen bendazol (dibazol) opened by N.V. Lazarev, showed that the drug has a number of positive properties: antiviral – stimulates immunity to the attack of infectious agents, being an inducer of endogenous interferon; antiproliferative – inhibits the replication of viruses inside the host cell; immunomodulatory – corrects violations of the protective functions of the body. Dibazol also has a mild effect after vaccination, stimulating the production of immunoglobulins. These properties of dibazol make it possible to recommend it and herbal adaptogens (tinctures of Eleutherococcus, Rhodiola rosea, Scutellaria Baicalensis) for the prevention of coronavirus infection.