A zinc complex of chelidonic acid (4-oxo-4H-pyran-2,6-dicarboxylic acid) was obtained by reaction with zinc oxide under isothermal conditions. Its composition was confirmed by elemental and thermogravimetric analyses, and its molecular structure was characterized using NMR and IR spectroscopy. Single-crystal X-ray diffraction revealed that the complex crystallizes as a one-dimensional coordination polymer, [ZnChel(H2O)4]n, in the triclinic space group P-1, featuring a distorted octahedral Zn(II) center coordinated by two chelidonate ligands and four water molecules. This six-coordinate arrangement contrasts with previously described tetra-coordinated Zn-chelidonate complexes. Quantum-chemical calculations and molecular dynamics simulations indicated that, in aqueous solution, Zn(II) preferentially forms a monodentate ZnChel(H2O)5 species, consistent with the solid-state coordination environment. The interaction of the complex with bovine serum albumin (BSA) was examined by fluorescence, UV-Vis absorption, and circular dichroism spectroscopy, revealing a mixed static-dynamic quenching mechanism, moderate binding affinity, and hydrogen-bonding/van der Waals contributions accompanied by alterations in BSA secondary structure. These results expand the structural chemistry of chelidonic acid and provide biophysical insight into the protein-binding behavior of zinc chelidonate, supporting its potential relevance as a zinc-based bioactive compound.

Currently, in agriculture, there is a tendency towards the partial replacement of chemical pesticides with microbiological plant protection products. In this work, we tested the ability of plant-growth promoting bacteria from the genus Azospirillum to reduce the negative effects of high concentrations of six different pesticides on wheat characteristics. Of the seven Azospirillum strains studied, five showed high resistance to at least one pesticide, and Niveispirillum irakense (formerly classified as Azospirillum until 2014) was one of the most resistant strains to all pesticides. In most cases, catalase activity increased in resistant strains in the presence of pesticides. Furthermore, we demonstrated that some of the most resistant Azospirillum strains (including N. irakense, A. brasilense, A. picis, A. thiophilum, and A. baldaniorum) can counteract pesticide-induced growth inhibition, suppress oxidative stress, as evidenced by a decrease in iron-induced chemiluminescence and the amount of oxidative damage to wheat seedling mtDNA in a pot experiment. However, the bacteria had no positive effect on the chlorophyll content of wheat seedlings. Azospirilla were found in the rhizosphere of wheat roots 3 months after a wheat planting in the field experiment. Pesticides led to a slight decrease in their quantity in the rhizosphere. Additionally, bacterial inoculation mitigated the pesticide-induced decrease in wheat biomass.

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.

This paper presents the results of the study of the effect of water with deuterium content of 750 ppm, used for simulation of the isotopic composition of water in ice caps at the poles of Mars, on oxidative processes in the liver tissue and blood of laboratory animals. It was found that prolonged consumption of deuterium-enriched water contributed to an increase in the deuterium content in blood plasma up to 487 ppm. As a result, increased antioxidant activity in the liver tissues and blood plasma was observed. In addition, the effect of a medium that contains 487 ppm of deuterium on the secondary structure of bovine serum albumin was also investigated in a model experiment. A decrease in intensity of circular dichroism and intrinsic tryptophan fluorescence spectra was found. This indicates that there are conformational changes in the structure of this protein at a time when the content of deuterium increases in the incubation medium. The results of our research point to the need to explore further the effect of drinking diet with the increased deuterium to (from 700 to 1000 ppm) on living systems, to explain the possibility for life on Mars.

The coordination compound [Mg(HCom)2(H2O)6]·2H2O (I) was obtained by the reaction of comenic acid (H2Com) with magnesium acetate in water. The formation of a new phase was confirmed by powder X-ray diffraction. The molecular formula of the compound was determined from energy dispersive X-ray fluorescence and thermogravimetry data. The thermo-oxidative stability of magnesium comenate was studied by simultaneous thermal analysis in air. The molecular structure of the complex was discussed on the basis of spectral data (NMR, IR, and UV spectroscopy) and studied in detail using X-ray diffraction (CCDC no. 2 207 835). Magnesium comenate crystallizes in the triclinic system, space group P 1̅, the structure is stabilized by intra- and intermolecular hydrogen bonds between the coordinated water molecules, acid anions, and [Mg(H2O)6]2+.

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.

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.

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.

We studied the effect of a low-frequency (LF) electromagnetic field (EMF) on the state of the antioxidant system of Wistar rats in vivo. It was found that changes in activity of antioxidant enzymes and H2O2 content in the blood plasma of rats exposed to LF EMF depended on the frequency of EMF. We propose a mechanism of the protective effects of low doses of ROS the generation of which is stimulated by LF EMF.

The effect of a reduced deuterium (D) content in the incubation medium on the survival of cultured neurons in vitro and under glucose deprivation was studied. In addition, we studied the effect of a decrease in the deuterium content in the rat brain on oxidative processes in the nervous tissue, its antioxidant protection, and training of rats in the T-shaped maze test under hypoxic conditions. For experiments with cultures of neurons, 7–8-day cultures of cerebellar neurons were used. Determination of the rate of neuronal death in cultures was carried out using propidium iodide. Acute hypoxia with hypercapnia was simulated in rats by placing them in sealed vessels with a capacity of 1 L. The effect on oxidative processes in brain tissues was assessed by changes in the level of free radical oxidation and malondialdehyde. The effect on the antioxidant system of the brain was assessed by the activity of catalase. The study in the T-maze was carried out in accordance with the generally accepted methodology, the skill of alternating right-sided and left-sided loops on positive reinforcement was developed. This work has shown that a decrease in the deuterium content in the incubation medium to a level of −357‰ has a neuroprotective effect, increasing the survival rate of cultured neurons under glucose deprivation. When exposed to hypoxia, a preliminary decrease in the deuterium content in the rat brain to −261‰ prevents the development of oxidative stress in their nervous tissue and preserves the learning ability of animals in the T-shaped maze test at the level of the control group. A similar protective effect during the modification of the 2H/1H internal environment of the body by the consumption of DDW can potentially be used for the prevention of pathological conditions associated with the development of oxidative stress with damage to the central nervous system.

The deuterium content modification in an organism has a neuroprotective effect during the hypoxia model, affecting anxiety, memory and stress resistance. The aim of this work was to elucidate the possible mechanisms of the medium D/H composition modification on nerve cells. We studied the effect of an incubation medium with a 50 ppm deuterium content compared to a medium with 150 ppm on: (1) the activity of Wistar rats’ hippocampus CA1 field neurons, (2) the level of cultured cerebellar neuron death during glucose deprivation and temperature stress, (3) mitochondrial membrane potential (MMP) and the generation of reactive oxygen species in cultures of cerebellar neurons. The results of the analysis showed that the incubation of hippocampal sections in a medium with a 50 ppm deuterium reduced the amplitude of the pop-spike. The restoration of neuron activity was observed when sections were returned to the incubation medium with a 150 ppm deuterium content. An environment with a 50 ppm deuterium did not significantly affect the level of reactive oxygen species in neuron cultures, while MMP decreased by 16–20%. In experiments with glucose deprivation and temperature stress, the medium with 50 ppm increased the death of neurons. Thus, a short exposure of nerve cells in the medium with 50 ppm deuterium acts as an additional stressful factor, which is possibly associated with the violation of the cell energy balance. The decrease in the mitochondrial membrane potential, which is known to be associated with ATP synthesis, indicates that this effect may be associated with the cell energy imbalance. The decrease in the activity of the CA1 field hippocampal neurons may reflect reversible adaptive changes in the operation of fast-reacting ion channels.

Research in recent years has shown that there is a close connection between the brain and the intestine through neuronal, endocrine and immune pathways. The introduction of probiotics into the diet of animals and humans helps to reduce the level of anxiety and depression, as well as inflammatory processes during emotional stress. The aim of this work was to study the effect of intragastric administration of Bifidobacterium adolescentis and Lactobacillus acidophilus on oxidative processes in the brain tissues and the level of anxiety in rats under conditions of normoxia and acute hypoxia with hypercapnia. Material and methods. The experiment was performed on 64 male Wistar rats aged 2.5 months (body weight from 240 to 270 g). The animals were divided into 4 groups: group 1 - control; 2 - hypoxia; 3 - hypoxia + probiotics; 4 - probiotics. There were 16 animals in each group; half of them participated in the behavioral test, and the other half in the biochemical studies. Rats of groups 3 and 4 were orally administered lyophilized bacteria Bifidobacterium adolescentis MC-42, Lactobacillus acidophilus A-97, and Lactobacillus acidophilus A-630 for 30 days before hypoxia. The daily dose of probiotics was 1×109 CFU per animal, administered in a volume of 1 ml. Acute hypoxia with hypercapnia was simulated by placing rats in airtight vessels with a capacity of 1 L before the first agonal inhalation. A day later, in the brain tissues oxidative processes were assessed by the chemiluminescence method and by the level of malone dialdehyde (MDA). The activity of catalase in brain tissues was also determined. The level of anxiety of rats was investigated in the «elevated plus maze» test. Results. Compared to other groups, more intensive free radical oxidation took place in the brain tissues of hypoxified animals that did not receive B. adolescentis and L. acidophilus. There was a significant increase in chemiluminescence intensity and MDA level by 38 and 15%, respectively, compared with the control. In the brain tissues of these animals, catalase activity was reduced by 10% (p<0.01). Moreover, in the group of rats treated with B. adolescentis and L. acidophilus and subjected to acute hypoxia, the value of the light sum of chemiluminescence was 22% lower (p<0.01) than in the hypoxified group without taking probiotics, while the concentration of MDA and catalase activity remained at the level of physiological norms and did not differ from control. Hypoxified animals receiving biomass of lactobacteria and bifidobacteria had also a lower level of anxiety and a higher exploratory activity, expressed in an increase in the number of entries in the open and closed arms, a longer stay in the open arms and the center of the maze, and more frequent performance of orientation reactions and hanging. Conclusion. Pre-hypoxic administration of B. adolescentis and L. acidophilus reduces the development of oxidative stress in rat brain tissues and reduces anxiety indices in the "elevated plus maze" test, thereby exhibiting antioxidant and anxiolytic effects.

The effect of long-term (42 days) introduction of deuterium-depleted water into the diet of rats on the functional state of the central nervous system under normal conditions and normobaric hypoxia with hypercapnia was studied. It was also established that the use of deuterium-de-pleted water both under normal conditions and after stressful exposure contributes to a sig-nificant decrease in the emotional anxiety of animals. Long-term use of deuterium-depleted water before hypoxic exposure (exposure to the amnestic factor) contributes to the preservation of learning and memory at the control level, i.e. has a pronounced protective antiamnesic effect.

The effects of prolonged (42 days) addition of deuterium-depleted water into rat’s diet on the functional state of the central nervous system in normal conditions and under conditions of normobaric hypoxia with hypercapnia were studied. It was also established that the use of deuterium-depleted water both in normal conditions and after exposure to oxidative stress contributes to a significant reduction in the emotional anxiety of animals. Prolonged use of deuterium-depleted water before hypoxic exposure (amnestic effect) helps to maintain learning and memory at the control level, i.e. it has a pronounced protective antiamnestic effect. In normal conditions, deuterium-depleted water does not affect the learning ability of animals.

Abstract—It is established that a medium with a reduced content of deuterium has no effect on the secondary structure of horseradish peroxidase and bovine serum albumin and caused no conformational changes in the structures of these proteins. The placement of these proteins in a buffer solution prepared based on deuterium-depleted water led to a decrease in the intensity of intrinsic tryptophan fluorescence, while the circular dichroism spectra remained virtually unchanged. A decrease in the content of deuterium in the reaction medium led to a decrease in the activity of the peroxidase oxidation reaction of o-dianisidine and luminal with hydrogen peroxide.

Using the rat hypoxia model, the imbalanced work of antiradical defense enzymes with insufficient dismutase activity in blood leading to the development of oxidative stress, which was more pronounced in animals receiving a natural drinking diet, has been confirmed on the basis of the comparative analysis of the antiradical defense enzyme functioning index. It has been observed that acute hypoxia in the brain tissues is characterized by the development of catalase deficiency and the risk of excessive hydrogen peroxide production. It has been demonstrated that a decrease in the D/H (deuterium/protium) ratio in the blood and brain reduces the severity of the impairment of antioxidant enzyme work in hypoxia.

The effect of deuterium-depleted water on oxidative processes in the rat brain under physiological or hypoxic conditions was studied. The results obtained by a tissue culture method that characterize the functional parameters of neurons under stress are also presented. Results on free radical processes in the rat brain tissues demonstrated that consumption of deuterium-depleted water over 2 weeks has a stress effect. The long-term consumption of deuterium-depleted water caused activation of non-specific protective systems. The effect of a saline solution prepared with deuterium-depleted water on a cerebellar tissue culture was also studied. When incubation occurred in a saline solution based on deuterium-depleted water, glucose deprivation and temperature stress (39°C) were found to result in increased cell death in the neuronal culture. The neuron death rates under physiological conditions were similar in the case of both 150 and 50 ppm deuterium. At the same time, the mitochondrial membrane potential of cerebellar neurons decreased in the deuterium-depleted medium. Thus, incubation of cerebellar neurons in the deuterium-depleted saline solution had no cytoprotective effect.