Anna A. Elkina

The structure, antioxidant and neuroprotective properties of lithium comenate (lithium 5-hydroxy-4-oxo-4H-pyran-2-carboxylate) were studied. Lithium comenate was obtained by reacting comenic acid (H₂Com) with lithium hydroxide in an aqueous solution. The structure of lithium comenate was confirmed via thermal analysis, mass spectrometry, IR, NMR and UV spectroscopy. The crystal structure was studied in detail via X-ray diffraction. The compound crystallized in a non-centrosymmetric space group of symmetry of the orthorhombic system Pna2₁ in the form of a hydrate, with three water molecules entering the first coordination sphere of the cation Li⁺ and one molecule forming a second environment through non-valent contacts. The gross formula of the complex compound was established [Li(HCom)(H₂O)₃]·H₂O. It has been established that lithium comenate has a pronounced neuroprotective activity under the excitotoxic effect of glutamate, increasing the survival rate of cultured rat cerebellar neurons more than two-fold. It has also been found that the pre-stress use of lithium comenate at doses of 1 and 2 mg/kg has an antioxidant effect, which is manifested in a decrease in oxidative damage to the brain tissues of mice subjected to immobilization stress. Based on the data available in the literature, we believe that the high neuroprotective and antioxidant efficacy of lithium comenate is a consequence of the mutual potentiation of the pharmacological effects of lithium and comenic acid.

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)₂(H₂O)₆]·2H₂O was established. This complex compound crystallizes with eight water molecules, six of which are the hydration shell of the Mg²⁺ cation, and two more molecules bind the [Mg(H₂O)₆]²⁺ aquacation with ionized ligand molecules by intermolecular hydrogen bonds. The packing of molecules in the crystal lattice is stabilized by a branched system of hydrogen bonds with the participation of solvate water molecules and oxygen atoms of various functional groups of ionized ligand molecules. With regard to the biological activity of magnesium comenate, a neuroprotective, stress-protective, and antioxidant effect was established in in vitro and in vivo models. In in vitro experiments, magnesium comenate protected cerebellar neurons from the toxic effects of glutamate and contributed to the preservation of neurite growth parameters under oxidative stress caused by hydrogen peroxide. In animal studies, magnesium comenate had a stress-protective and antioxidant effect in models of immobilization–cold stress. Oral administration of magnesium comenate at a dose of 2 mg/kg of animal body weight for 3 days before stress exposure and for 3 days during the stress period led to a decrease in oxidative damage and normalization of the antioxidant system of brain tissues against the background of induced stress. The obtained results indicate the advisability of further studies of magnesium comenate as a compound potentially applicable in medicine for the pharmacological correction of conditions associated with oxidative and excitotoxic damage to nerve cells.

Alginates varying in modifying additives (primarily, chitosan) and physical treatment methods are used to design prototypes of innovative wound dressings. The aims of the study were to create a prototype sodium alginate fabric wound dressing with silver nanoparticles (AgNPs) subjected to ten freeze–thaw cycles, to assess its properties, and to evaluate its efficacy in treating the purulent wound process in rats. The original technology of ten freeze–thaw cycles was shown to significantly increase the AgNP amount in the sodium alginate wound dressing, primarily by increasing the amount of AgNPs no larger than 15 nm in diameter, which exert the highest antibacterial activity. The wound dressing with AgNPs reduced the metabolic disturbances in the local function of the nonspecific defense system. On days 3 and 5 after wounding, free radical oxidation indices were more favorable and the levels of antioxidant enzymes (catalase and superoxide dismutase (SOD)) in wound tissue were lower than observed upon application of a wound dressing with AgNPs, but without alginate, or after daily wound debridement without using alginate or AgNPs.

Water containing 750 ppm deuterium was used to simulate the isotopic composition of water in ice caps at the poles of Mars and tested for effect on oxidative processes in the liver and blood of laboratory animals. Prolonged consumption of deuterium-rich water was found to increase the deuterium content in the blood plasma to 487 ppm. Higher antioxidant activity was consequently observed the liver and blood plasma. The effect of a medium containing 487 ppm deuterium on the secondary structure of bovine serum albumin (BSA) was additionally studied in a model experiment. Lower intensities were observed in circular dichroism (CD) and intrinsic tryptophan fluorescence spectra, indicating that conformational changes arose in albumin structure when the deuterium content increased in the incubation medium. The study provides a basis for further research of how drinking water with a higher deuterium content (700–1000 ppm) affects living systems, to understand the possibility of life on Mars.

Meconic, comenic, chelidonic, and kojic acids are the main representatives of gamma-pyronic acids. It was found that comenic acid has a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. The neuroprotective effect of meconic acid has not been explored. The aim of this study was to investigate the neuroprotective potential of meconic acid on an in vitro ischemic stroke model, as well as on the basis of its physicochemical properties. A primary neuro-glial culture was obtained from the cerebellum of 7- to 8-day-old Wistar rats by mechanical dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using a model of glutamate toxicity and oxygen–glucose deprivation. The antioxidant activity of meconic acid was studied by quantum mechanical calculations and experimentally in the citrate-phosphate-luminol model system by chemiluminescence analysis. The chelating properties of meconic acid with respect to Fe³⁺ in solutions were studied by the Job’s method. Meconic acid has been found to have a protective effect on in vitro models of ischemia. It caused a decrease in the level of intracellular calcium and restoration of the membrane potential of mitochondria in the culture of cerebellar neurons under glutamate exposure and an increase in the percentage of living cells under oxygen–glucose deprivation. Meconic acid had a high calculated antioxidant potential, as was confirmed experimentally. With an increase in pH of the medium, a stepwise binding of meconic acid with Fe³⁺ occurred with the formation of complexes of different ligand/metal ratios. At physiological pH, the resulting complex had a composition with the ratio 1 : 3. The revealed antioxidant, chelating, and cytoprotective effects of meconic acid provide a basis for further study of the possible neuroprotective properties of this compound in experiments in vivo; the data on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on this acid.

The effect of single substitutions of protium for deuterium in hydrogen bonds between pairs of nitrogenous bases on the open states occurrence probability at high critical breaking energies of these bonds has been studied. The study was carried out using numerical methods based on the angular mathematical model of DNA. The IFNA17 gene was divided into three approximately equal parts. A comparison of the open states occurrence probability in these parts of the gene was done. To improve the accuracy of the results, a special data processing algorithm was developed. The developed methods have shown their suitability for taking into account the occurrence of open states in the entire range of high critical energies. It has been established that single ²H/¹H substitutions in certain nitrogenous bases can be a mechanism for maintaining the vital activity of IFNA17 under critical conditions. In general, the developed method of the mathematical modeling provide unprecedented insight into the DNA behavior under the highest critical energy range, which greatly expands scientific understanding of nucleobases interaction.

The effect of water with a high negative oxidation–reduction potential (ORP) on the physiological parameters of juvenile North African catfish (Clarias gariepinus) has been studied. The research has revealed that the reduction of the water ORP from +150…+250 to –600…–500 mV using an electromembrane generator without changing the salt composition at a slight pH variation with an exposure of 30 and 60 min once a day has a positive effect on the main biological parameters of juvenile North African catfish. The biomass growth was 756.6 g in the control group and 1004.2 g in the experimental group (30 min treatment). Fish individuals of the smallest size range (1.0–2.9 g) were most representative in weight in the control group (38%). In the experimental groups, it was 22.6 and 18.3% and most of the individuals were in the range of 3.0–4.9 g (38.3 and 44.1%, respectively). It has been revealed that the highest efficiency is achieved after treating the aquatic environment for 30 min.

The formation and dynamics of the open states in a double-stranded DNA molecule are largely determined by its mechanical parameters. The main one is the torque. However, the experimental study of DNA dynamics and the occurrence of open states is limited by the spatial resolution of available biophysical instruments. Therefore, in this work, on the basis of a mechanical mathematical model of DNA, calculations of the torque effect on the process of occurrence and dynamics of open states were carried out for the interferon alpha 17 gene. It was shown that torsion action leads to the occurrence of rotational movements of nitrogenous bases. This influence is nonlinear, and an increase in the amplitude of the torsion action does not lead to an automatic increase in the amplitude of rotational movements and an increase in the zones’ open states. Calculations with a constant torsion moment demonstrate that open states zones are more often formed at the boundaries of the gen and in regions with a predominance of A–T pairs. It is shown, that for the occurrence of open states in the part of the gene that contains a small number of A–T pairs, a large amount of torque is required. When the torque is applied to a certain region of the gene, the probability of the formation of the open state depends on the content of A–T pairs in this region, the size of this region, and on the exposure time. For this mathematical model, open states zones can be closed when the torsion action stops. The simulation results showed that the values of the torsion moment required for the appearance of open states zones, in some cases, are close to experimentally measured (13–15 pN·nm).